THE INSPIRING TALE Of DR. KYRI MOSLEY—fROM EWING SARCOMA DIAGNOSIS TO fOUNDING KYRI’S KOOKIES
BY NSISONG ASANGA
Dr. Kyri Mosley was a busy mother of two working as a psychologist in the healthcare field when she noticed strange symptoms on her right pelvis and leg. Shortly after, she received a diagnosis of stage 4 Ewing’s sarcoma, with a prognosis that was initially deemed poor. However, through exceptional medical care and her unwavering hope, Dr. Mosley defied the odds and achieved full remission. Following her recovery, she founded Kyri’s Kookies, an organic, luxury, black-owned cookie company that has been acclaimed by Oprah, Good Morning America, Forbes, and numerous other prominent platforms.
Kyri posing with her cookies, photo courtesy of Dr. Kyri Mosley
Oncology Compass spoke with her to get details of her inspiring journey and share them with you.
OC Digest: Let’s talk about your diagnosis phase, how did you know you had cancer?
Dr. Kyri Mosley: In late August 2019, I began to experience pains in my right pelvic wall, on the right side of my body and my right leg was swelling. Before that, I had traveled a lot for my company at the time, so I was surprised that my legs were swelling and the pain was so intense.
I went to the doctor and they thought it could be a urinary tract infection. I’m in the medical field and I was skeptical. I told them I had no other symptoms pointing in that direction.
I consulted two additional doctors, and the third offered to conduct a urine culture and follow up with me if I did not experience any relief within the next three days. Less than two days later he contacted me and said, “You are right, it is not a UTI.” Then he said, “I will send you to see a female urologist so she can take a look.”
I went to the female urologist and she examined me, I was in so much pain. She asked me if I felt anything and I did, I felt her pressing on something. She advised that I needed an immediate CT scan with contrast. However, due to my allergy to contrast, we had to proceed with a standard CT scan instead.
The next day, she said, “I don’t like what I see, I am going to refer you to another doctor.” Eventually, she sent me to another doctor without letting me know their specialty. I looked the doctor up and found out they were an oncologist. So I asked her about it and she said “I didn’t want to alarm you but I am very concerned about the masses I saw.”
The biopsy was conducted the following day, and it revealed that I had a rare cancer called sarcoma, which was at stage 4. After further analysis, they identified it as Ewing’s sarcoma. The cancer was located in my pelvic wall and had also spread to my lungs.
The doctor treating me said “The prognosis is not good. If I were you I would go to Emory Healthcare In Georgia.” He hadn’t been able to help any of his patients survive so he felt my chances were best with Emory Healthcare.
This was a tremendous relief for me as I had a home in Georgia. Although I had recently built my home, I was staying elsewhere with my girlfriend because I didn’t want to live there alone. Additionally, I had professional connections at Emory University, having collaborated on an infectious disease publication with them three years prior. I have a deep appreciation for that hospital.
When I got to Emory, I met Dr. William Reed and I had a warm but honest discussion about my care. He asked if my locs were my real hair, and when I said yes he shook his head. He told me I was going to lose all of it after my first dose. The treatment regimen I would be having was quite aggressive. I would need to be admitted to the hospital for five to seven days and infused for 120 hours at a time. And all my hair would be gone after the first week.
So when I left there, I just went and cut my hair and donated to Locs of Love. I had a teeny-weeny afro and it was gone after the first treatment. But it felt good to have control over that part of the process. I know that if I had to touch my head and see big pieces of my hair fall out, that would have been too much for me.
OC Digest: But, as we can see, you grew it all back!
Dr. Kyri Mosley: I did! It’s all back now.
OC Digest: Tell us a little more about the treatments you were given.
Dr. Kyri Mosley: I was on five days of treatment every three weeks. It was a combination of three drugs infused, Ifosfamide, Vincristine, and Doxorubicin (the one they call the Red Devil). They say it is hardly used anymore because of how harsh it is on the human body. I had treatments from 2019 to 2020.
After that, I had radiation therapy which was proton therapy. However, my body reacted severely to the radiation therapy. My body turned black like a piece of burnt wood. I was experiencing side effects normally seen by week six in my second week. I still had to go through it. It was rough.
OC Digest: How do you feel now? Do you still experience any symptoms?
Dr. Kyri Mosley: I have severe lymphoedema in my right leg currently. I wear a compression garment every single day because my leg will expand to twice its size if I don’t. And it’s extremely painful. Also, I have nerve damage in my right leg. I also get a stent every four to six weeks in my kidney because of the radiation.
So, I got a lot of damage as a result of everything, but I am here.
OC Digest: That’s amazing. What kept you going through it?
Dr. Kyri Mosley: My kids and my faith. I have two children, a boy and a girl. My daughter was 26 years old, and my son was 21 years old. I just wanted to be there for my children.
I felt like I had so much more to give and I wasn’t ready to go. I am also a praying woman. I told God I wasn’t finished.
OC Digest: And how did you start Kyri’s Kookies?
Dr. Kyri Mosley: I had been baking cookies and giving them away for 12 years. My first boyfriend was in the military, as were my sister and uncle. So I always had a heart for soldiers and their sacrifice for us.
In 2019 I was going through my divorce and I started baking with my son. It was a great way to get out of myself and not focus on what I was going through. I would bake cookies, banana bread, and all kinds of treats for soldiers. It helped me to think of others and send them gifts. It helped me heal.
OC Digest: And how did it become a business?
Dr. Kyri Mosley: In April 2021, I went into full remission and decided to do cookies full-time. So I started Kyri’s Kookies. I felt like I had been given a second opportunity and I wanted to spend it on something I loved doing, something that allows me to encourage people. My grandmother raised me and she said I had always been keen to encourage others. Even as a kid, I would give my sister a big piece of cake. I have always been this way and Kyri’s Kookies just fuels that for me.
OC Digest: And do you still serve just the military?
Dr. Kyri Mosley: Now, we serve everyone. If you want to send encouragement to someone, you get in touch with us and place an order. People send me their stories, they tell me people they want to encourage and I send cookies to them. We try to encourage people not to wait for holidays or birthdays, just continue to show gratitude all the time. Giving, gratitude and generosity are our mantras.
OC Digest: What have the highlights of your business been?
Dr. Kyri Mosley: The first highlight was getting our first client when we were just six months old, which was Marriott Hotels.
Three months later, we secured Hyatt Hotels as a client. They remain our largest client today, with us providing cookies for their luxury hotels and cookie dough for on-site baking. In November 2023, we were honored to be named one of Oprah’s Favorites.
This was amazing, I was like, does it get better than this? It’s the highest honor you can receive to know your product has been chosen for its excellence and quality.
OC Digest: What words do you have for others facing a condition with a poor prognosis?
Dr. Kyri Mosley: First, I am a spiritual person. I think the important thing is to surround yourself with positivity even if you have to give it to yourself in the form of daily affirmations that can remind you to continue to fight. Stay positive. Stay close to your creator.
Dr. Kyri Mosley makes healthy and nutritious sweet delights, photo courtesy of Dr. Kyri Mosley
LObbYING fOR CHANGE
FIRST-LINE DEFENSE
CANCER DIAGNOSES FAST-TRACKED: UNLOCKING THE POWER Of DIRECT PRIMARY CARE
BY MARIJA GEIST
Dr. Hamawi, a Board- Certified expert in Internal Medicine and Pediatrics, has embraced the Direct Primary Care (DPC) model in her Worcester, MA practice.
This approach prioritizes patient well-being through more personalized, convenient care, enabling enhanced interactions between Dr. Hamawi and her patients.
DPC eliminates the interference of insurance in the patient-doctor relationship, offering a membership system for a flat monthly fee that covers a wide range of medical services.
This model fosters a closer, more responsive healthcare experience, focusing on preventive care and chronic disease management.
Dr. Tatiana Hamawi, photo courtesy of Dr. Tatiana Hamawi
We depend on our medical providers to help us stay healthy. Over the past decade, there has been a concerning increase in the delay of cancer diagnoses, posing a significant challenge to public health. The consequences of delayed cancer diagnosis are profound, leading to more advanced disease stages at the time of detection, diminished treatment options, and poorer overall outcomes for affected individuals. Recent data suggest that even a four-week delay in cancer treatment is associated with increased mortality across surgical, systemic treatment, and radiotherapy indications.1
The current medical system in the United States is often criticized for its predominant focus on treating diseases rather than prioritizing prevention. The emphasis on treatment is fueled by the fee-for-service reimbursement model, compensating healthcare providers for specific services. Additionally, network-based insurance models contribute to this trend, imposing administrative burdens on physicians and raising overhead costs.
This system incentivizes primary healthcare providers to manage a high patient volume, limiting time for each individual. Swift referrals to specialists occur, who are then motivated to prioritize procedures over preventive measures due to financial considerations.
The fragmented nature of the healthcare system, with separate entities handling primary care, specialists, and insurance, creates barriers to seamless preventive care coordination.
Dr. Hamawi of Alpha- Omega Direct Primary Care, LLC, is Board Certified in Internal Medicine (for adults) and Pediatrics (for children) and has been serving families in Massachusetts for over 22 years. She understands the importance of personalized and accessible primary care. She believes in building strong doctor-patient relationships and providing a high level of care tailored to each individual’s needs. www.aomedical.com
Shifting towards a more preventive healthcare model requires addressing systemic issues, aligning financial incentives, and fostering a cultural shift that values long-term health outcomes over immediate and episodic interventions. DPC may be the innovative solution to this problem. It focuses on providing personalized, accessible, affordable, and comprehensive care to patients. As a result, DPC can play a significant role in preventing delays in cancer diagnosis through several key features and benefits.
What is direct primary care in a nutshell? Simply put, it’s a membership-based model that allows individuals and families timely and direct access to their primary care provider for a low monthly fee. The patient pays a small payment directly to the doctor, who now works for them, not the insurance plan. This fee covers many services, including office visits, preventive care, and certain procedures.
With a DPC membership, there are no insurance hassles, co-pays, or deductibles, making it a convenient and cost-effective option for covering primary care services. The membership model encourages the patient to stay in touch instead of trying to avoid a co-pay or a deductible, further strengthening the bond between doctor and patient.
Extended and unrushed consultations: Direct Primary Care enhances the doctor-patient relationship. DPC providers have smaller panels and are not burdened by administrative hassles. They are free to spend more time with each patient, getting to know them on a deeper level.
The extra time allows for more comprehensive care, as the provider can better understand the patient and create a personalized care plan accordingly. This can all be crucial in identifying subtle symptoms indicative of cancer.
Comprehensive discussions about family history, lifestyle, and risk factors can help assess the likelihood of cancer and prompt further diagnostic testing.
Access to primary care: Direct Primary Care also increases accessibility to health care. The patient can access their provider whenever needed, whether through same-day or next-day in-person visits, phone calls, virtual consultations, or even direct texting.
The convenient and easy access to the doctor means minor health concerns can be addressed quickly and efficiently, preventing them from becoming more serious. The ability to connect remotely also sidesteps the need to take a day off from work, again increasing the likelihood of connecting with the doctor. Early cancer symptoms may be subtle, and quick access to primary care can facilitate early detection and investigation of potential issues.
Regular and preventive screenings: DPC providers often focus on preventive care, including regular screenings. Screening tests can help detect cancer at early stages, often before symptoms appear. Direct primary care models may have more flexibility in ordering and performing screenings without the bureaucratic hurdles in traditional healthcare systems.
Patient education: The success of any healthcare model depends on the commitment of both healthcare providers and patients to prioritize preventive care and early intervention.
DPC providers emphasize patient education, empowering individuals to recognize potential signs of cancer and seek timely medical attention. Increased patient awareness can lead to proactive health-seeking behaviors and early reporting of symptoms.
Dr. Hamawi with her patients, photo courtesy of Dr. Hamawi
Care coordination: DPC providers have more time and resources for care coordination. In the context of cancer diagnosis, this can involve prompt referrals to specialists, coordination of diagnostic tests, and collaboration with oncologists. Timely communication and collaboration between healthcare providers can expedite the diagnostic process.
Cost transparency and affordability: DPC models provide cost transparency and affordability, reducing financial barriers to seeking healthcare. DPC providers can offer reduced prices, making access to concierge-style services more affordable. Anything outside the monthly fee is competitively priced and disclosed upfront.
There are no surprise bills or hidden medical expenses. Patients are more likely to seek medical attention promptly if they know the costs are reasonable and predictable. Affordability can also encourage patients to undergo recommended screenings and diagnostic tests without hesitation.
Patients also benefit through arrangements DPC providers have with other local providers for low-cost lab work and imaging, providing increased access to services like getting that MRI that the insurance plan might have denied.
In conclusion: The current state of the U.S. medical system, with its emphasis on treating diseases rather than preventing them, stems from a complex web of financial incentives, a fee-for- service reimbursement model, and a fragmented healthcare structure.
However, Direct Primary Care (DPC) is a promising solution to address these systemic issues. With its focus on personalized, accessible care, DPC is revolutionizing the patient experience.
Its emphasis on preventive care, regular screenings, patient education, and efficient care coordination within the DPC mode, can significantly contribute to the early detection and prevention of diseases, including cancer.
DPC’s cost transparency and affordability make preventive healthcare accessible, mitigating financial barriers and encouraging proactive health-seeking behaviors.
A game-changer in healthcare, DPC represents a shift towards a model that values long-term health outcomes, aligning with the need for a cultural transformation in healthcare priorities.
Through its innovative approach, Direct Primary Care stands poised to lead the charge in reshaping the healthcare landscape towards a more preventive and patient-centric future.
ONCOLOGY BREAKTHROUGHS
BREAST CANCER
HER2-POSITIVE ADVANCEMENT: THE ROLE Of PYROTINIb, A POTENT IRREVERSIbLE PAN-HER INHIbITOR
BY ANNE JÄKEL
HER2-positive breast cancer is identified by the overexpression of the human epidermal growth factor receptor 2 (HER2), often leading to aggressive tumor growth and less favorable outcomes.1 Targeted therapy has revolutionized the treatment of this subtype, markedly enhancing survival rates.2 Among these therapies, Pyrotinib, a potent irreversible pan-HER inhibitor, has shown considerable promise, especially when used in conjunction with other anticancer agents.3-6
Breast cancer cells, photo credit: National Cancer Institut, Unsplash
Recent research has been directed toward evaluating Pyrotinib in combination with various chemotherapeutic agents and HER2 inhibitors to boost its effectiveness, particularly for those patients who have developed resistance to initial treatments like trastuzumab. Several clinical trials examined the efficacy and safety profiles of Pyrotinib in different combinations, offering insights into its role in treating HER2- positive breast cancer across several patient populations.
Innovative therapy for trastuzumab-resistant HER2-positive breast cancer: The PICTURE study outcomes The PICTURE study, a phase 2 trial conducted across 16 sites in China, focused on treating HER2-positive advanced breast cancer patients who exhibited resistance to trastuzumab.7
This cohort had limited effective treatment options, as many participants had also received pertuzumab. In the study, 100 patients were administered oral pyrotinib in combination with capecitabine, continuing until disease progression or intolerable toxicity occurred.7
The study’s primary measure, progression-free survival (PFS), impressively reached a median of 11.8 months, surpassing the pre-defined efficacy boundary of 8.0 months. Additionally, the objective response rate was 70.0%, with a disease control rate of 87.0%. These results underscore a significant therapeutic effect, particularly notable given the typically poor prognosis associated with trastuzumab resistance.7 In terms of safety, the combination therapy of pyrotinib and capecitabine was generally well tolerated.
The most common serious adverse event was diarrhea, impacting 24% of the patients. Effective management of side effects, including dose reductions and symptomatic treatments, enabled most patients to continue with their therapy uninterrupted.7
These findings suggest that the combination of pyrotinib and capecitabine represents a promising therapeutic alternative for patients with trastuzumab-resistant HER2- positive advanced breast cancer. The considerable extension in PFS and the high response rates make this therapy a compelling option for such challenging cases. Moreover, its manageable safety profile allows for its administration with a reasonable expectation of patient tolerance, presenting a valuable addition to the array of treatments available against this aggressive form of breast cancer, particularly in scenarios where other therapies have failed.
Enhanced first-line therapy for HER2-positive metastatic breast cancer: Insights from the PHILA study The PHILA study, a pivotal phase 3 trial, examined the efficacy of integrating pyrotinib with the established trastuzumab and docetaxel regimen for treating metastatic HER2-positive breast cancer. Conducted across 40 centers in China, this randomized, double-blind trial enrolled 590 female patients who had not received prior treatment for their metastatic condition. The study aimed to improve first-line treatment efficacy by harnessing the complementary mechanisms of HER2 targeting agents. Participants were randomized to receive either pyrotinib or a placebo alongside trastuzumab and docetaxel, starting on the first day of each 21-day cycle, with treatments double-blinded to maintain the integrity of results.8
The primary endpoint, PFS, was significantly enhanced in the pyrotinib group, with a median PFS of 24.3 months compared to 10.4 months in the placebo group. The trial reported a hazard ratio of 0.41, pointing to a robust effect of the treatment.8
Safety considerations were also critical, as treatment-related adverse events of grade 3 or higher occurred in 90% of the pyrotinib group, notably higher than 76% in the placebo group. Despite the high incidence of severe adverse events, such as diarrhea and hematological effects, these were manageable with appropriate medical interventions.8
The PHILA study’s findings advocate for incorporating pyrotinib into first-line treatment strategies, offering a new dual anti-HER2 strategy that could significantly improve outcomes for patients with metastatic HER2- positive breast cancer. By extending PFS and managing safety effectively, pyrotinib may well establish a new benchmark in the treatment of this challenging disease.
Reassessing second-line therapy for HER2-positive metastatic breast cancer: Findings from the PHOEBE trial The PHOEBE trial investigated the effectiveness and safety of pyrotinib in combination with capecitabine versus lapatinib with capecitabine for patients with HER2-positive metastatic breast cancer who had previously been treated with trastuzumab and taxanes.
Photo credit: Freepik.com
This phase 3, multicenter, open-label, randomized, controlled trial played a crucial role in addressing the need for potent second-line treatment options in this patient population. Participants, all of whom had pathologically confirmed HER2-positive metastatic breast cancer, were assigned to receive either the pyrotinib-capecitabine duo or lapatinib-capecitabine combo in 21-day treatment cycles.9
Efficacy analysis from the trial showed that the pyrotinib plus capecitabine group experienced significantly longer progression-free survival (PFS) compared to their counterparts receiving lapatinib plus capecitabine, with median PFS times of 12.5 months versus 6.8 months, respectively.9
Safety assessments highlighted that the most prevalent severe adverse events were diarrhea and hand-foot syndrome. Despite these challenges, effective dose adjustments and supportive care strategies were implemented to mitigate these effects, enhancing overall patient comfort and treatment adherence.9
The outcomes of the PHOEBE trial indicate a potential paradigm shift in the management of HER2-positive metastatic breast cancer, especially for those previously treated with trastuzumab and taxanes.
The notable improvement in PFS seen with the pyrotinib-capecitabine regimen suggests that this combination might become a new standard of care, offering renewed hope and improved outcomes for patients requiring effective second- line therapeutic options.
In conclusion, these trial results indicate that pyrotinib has shown significant potential to enhance clinical outcomes in HER2-positive breast cancer, marking a major advancement in oncology that could reshape future treatment standards.
ONCOLOGY BREAKTHROUGHS
PROMISING TREATMENT DELIVERY
INNOVATIVE NANObUbbLES: A STEP fORWARD IN LUNG CANCER TREATMENT
BY KRISTINA OLUJIĆ MILOŠEVIĆ
Biomedical Engineering Professor Ke Cheng and his team from Columbia University demonstrated that exosomes, a type of drug delivery carrier, significantly advance lung cancer treatment. Their research, published in Nature Nanotechnology, shows that using exosomes in an inhalation treatment strategy directly delivers anti-lung cancer cargo IL-12 mRNA to the lungs. This method enhances IL-12 expression with reduced toxicity compared to other drug delivery methods and could improve patients’ quality of life by allowing inhalation treatment instead of intratumoral injections.1
Promising tumour suppressors IL-12 cytokines, which are tiny signalling proteins, possess a strong promise as tumour suppressors. However, the transportation of IL-12 mRNA to lungs presents a challenge. Over time, scientists have been using liposomes or lipid nanoparticles (LNPs) to transfer mRNA, but this technology has several drawbacks. Some of the disadvantages include a lack of tissue homing, in which the particles do not reach their intended organs, and concerns regarding potential toxicity over long-term exposure.1
An innovative approach that overcomes limitations Dr. Cheng’s research group created nanobubbles, exosomes that showed to be superior drug delivery carriers than liposomes and LNPs for specific implications. At this point, clinicians could only use IL-12 to treat cancer by injecting it directly into the tumour or the bloodstream.
In mouse experiments, the researchers discovered that inhaling IL-12 mRNA in exosomes might not only transport locally concentrated IL-12 into the lungs, but also contribute to combating cancer with fewer adverse effects.
The inhalation approach is more effective than other methods of delivering mRNA, such as liposomes and LNPs, in terms of increasing IL-12 concentrations precisely where they are required.1 “In this new study, we show that inhaled exosomes can efficiently reach the lung and deliver an anti-lung cancer cargo, IL-12 mRNA. This is a major step forward in advancing the development of new inhalable drugs to treat lung cancer, which has one of the lowest five-year survival rates in the world,” said Dr. Cheng.1
Immune cells as powerful defenders Delivery of IL-12 mRNA to the lungs can activate lung immune cells, transforming them into powerful defenders that release substances capable of directly targeting and destroying tumour cells. Cytokine IL-12 helps stimulate immune cells to “remember” the unique characteristics of tumour cells. As a result, if the tumour tries to attack again, these well-informed immune cells are ready to recognize and eliminate the tumour rapidly.
Furthermore, these powerful immune cells may be able to transfer their newly learned information to other, untrained immune cells throughout the body, forming an army of defenders. More precisely, if tumour cells try to grow and spread outside of their original position, these prepared immune cells can detect and eliminate them. This mechanism provides a body-wide defence against cancer.1 The treatment strategy is supported by Dr. Cheng and colleagues research which discovered that mice inhaled with IL-12 mRNA via exosomes showed lung tumour reduction as well as increased resistance to tumour rechallenges.1
Future directions Dr. Cheng’s research group is currently collaborating with physicians from the Columbia University Irving Medical Center. The aim of this collaboration is implementation of the findings into the clinic practice in order to improve lung cancer treatment and quality of patients’ life.1
ONCOLOGY BREAKTHROUGHs
PRIMARY ANALYSIS OF THE PHASE 3 HER2CLIMB-02
TUCATINIb AND TRASTUZUMAb EMTANSINE IN HER2+ METASTATIC bREAST CANCER
BY HV MEDICAL
Efficacious therapies for patients with HER2+ breast cancer with brain metastases are limited and remain a significant unmet need. A therapeutic that is increasingly showing promise of filling this void is tucatinib, which is administered as part of a combination therapy alongside trastuzumab and capecitabine. This combination therapy excelled in Phase 2 trials, demonstrating a significantly better progression-free survival (PFS) and overall survival outcome compared with placebo in patients with HER2+ metastatic breast cancer, including those with brain metastases. Primary analysis from the Phase 3 HER2CLIMB-02 trial appear equally impressive, whereby a combination treatment of tucatinib and ado-trastuzumab emtansine (T-DM1) extended PFS by approximately three months compared with T-DM1 treatment in isolation.
Photo credit: Unsplash
Introduction Despite significant progress in the treatment of breast cancer over the last two decades, it is still the second largest contributor to cancer mortality globally. About 20% of invasive breast cancers show an over-expression of the HER2 receptor, which manifests as a more aggressive phenotype, resulting in a greater probability of relapse.1
As a result of this phenotype, it is estimated that 30–50% of patients with metastatic breast cancer will develop brain metastases.2 Treatment for brain metastases in patients with HER2+ breast cancer includes local therapies such as surgical resection and whole brain radiotherapy.3
Patients with HER2+ breast cancer have a very poor prognosis, however, as targeted anti-HER2 therapies and dual HER2 antibody blockade have evolved, survival of patients with HER2+ metastatic breast cancer is fast approaching five years.4
Despite this, an efficacious therapy of this kind is still a significant unmet need. One therapy that has shown promise over the last few years is tucatinib (Tukysa®), which has demonstrated significant efficacy in patients with this type of cancer.
Tucatinib Tucatinib is an investigational, oral tyrosine kinase inhibitor that is highly selective for the intracellular kinase domain of the HER2 receptor, with minimal inhibition of epidermal growth factor receptor (EGFR).3 Tucatinib is more than 1000 times more selective for HER2 than for EGFR, inhibition of the latter contributes to side effects such as rash and diarrhea.5
Tucatinib is given as part of a multi therapy alongside trastuzumab, a monoclonal antibody against HER2, and capecitabine. Trastuzumab binds to the extracellular domain of HER2, working in synergy with tucatinib to provide a dual HER2 blockade, whilst capecitabine is an antimetabolite chemotherapy, which interferes with the cancer cell’s ability to repair DNA.5-7 This combination was investigated in the Phase 2 HERCLIMB trial, demonstrating significant efficacy in patients with HER2-positive metastatic breast cancer, including those with brain metastases.3
Positive Phase 2: HER2CLIMB results The HER2CLIMB trial evaluated tucatinib combined with trastuzumab and capecitabine in patients with HER2+ metastatic breast cancer who were previously treated with trastuzumab, pertuzumab, and trastuzumab emtansine.
The trial enrolled 612 patients from 15 countries; patients were randomized to receive 300mg tucatinib twice daily (n=410), or placebo twice daily (n=202), in combination with trastuzumab (6mg per kg of body weight every 21 days) and capecitabine (1000mg per m2 of body surface area, twice daily on days 1–14 of each 21-day treatment cycle).
In the primary endpoint analysis population (n=480), 320 were assigned to the tucatinib-combination group, and 160 to the placebo- combination group. In the total population, 291 patients (47.5%) had brain metastases at baseline. The median duration of follow-up was 14 months.3
In the total study population, PFS at one year was 33.1% in the tucatinib combination group and 12.3% in the placebo-combination group (hazard ratio [HR] for disease progression or death, 0.54; 95% confidence interval [CI], 0.42 to 0.71; P<0.001), and the median duration of PFS was 7.8 months and 5.6 months, respectively. Overall survival after two years was 44.9% in the tucatinib-combination group and 26.6% in the placebo- combination group (HR for death, 0.66; 95% CI, 0.50 to 0.88; P=0.005), and the median overall survival was 21.9 months and 17.4 months, respectively.3
In patients with brain metastases, PFS after one year was 24.9% in the tucatinib-combination group and 0% in the placebo-combination group (HR, 0.48; 95% CI, 0.34 to 0.69; P<0.001), and median PFS was 7.6 months and 5.4 months, respectively. Diarrhea and elevated aminotransferase levels of ≥ grade 3 were more common in the tucatinib- combination group than in the placebo-combination group.3
The HER2CLIMB trial demonstrated that in heavily pretreated patients with HER2+ metastatic breast cancer, including those with brain metastases, treatment with tucatinib in addition to trastuzumab and capecitabine resulted in better PFS and overall survival outcomes when compared with placebo.3
Off the back of these impressive results, in April 2020 the FDA approved tucatinib in combination with trastuzumab and capecitabine for use in adult patients with advanced unresectable or metastatic HER2+ breast cancer, including patients with brain metastases.8
The announcement of the Phase 3 HER2CLIMB-02 trial, which assesses tucatinib in combination with T-DM1, broke last year, with primary analysis of the trial being reported recently at the San Antonio Breast Cancer Conference.9
Phase 3 HER2CLIMB-02: Primary analysis The randomized, double-blind, placebo-controlled Phase 3 HER2CLIMB-02 trial enrolled 463 patients with unresectable locally advanced or metastatic breast cancer who were previously treated with trastuzumab or a taxane in any setting. Patients were randomly assigned to either 21-day cycles of tucatinib (300mg twice daily) and T-DM1 (3.6mg/kg every three weeks), or T-DM1 and placebo. A proportion of 44.1% of all patients had baseline active or stable brain metastases. The median follow up was 24.4 months.10,11
Early analysis has demonstrated that tucatinib and T-DM1 combination therapy extended PFS by about three months compared with T-DM1 alone.
After 24.4 months, the median time to disease progression or death was 9.5 months with tucatinib plus T-DM1 and 7.4 months with T-DM1 alone (HR, 0.76; P=0.0163), highlighting a 24% likelihood of reducing disease progression or death with the combination.10,11
In patients with brain metastases at baseline, the median time to disease progression or death was 7.8 months with the combination of tucatinib plus T-DM1 and 5.7 months with T-DM1 alone (HR, 0.64), highlighting a 36.1% risk reduction of disease progression or death in favor of the combination treatment.
The most common treatment- emergent adverse events more frequently reported in the experimental arm included nausea, diarrhea, and fatigue.10,11
Concluding remarks Recent primary analysis from the HER2CLIMB-02 trial further supports the efficacy of tucatinib in patients with HER2+ metastatic breast cancer and brain metastases, building on the impressive results seen in the Phase 2 HER2CLIMB trial.
Speaking about the primary analysis, Sara A. Hurvitz, MD, FACP, of the University of Washington Fred Hutchinson Cancer Center in Seattle, said, “The HER2CLIMB-02 and HER2CLIMB studies provide level 1 evidence for the use of tucatinib in patients with active or progressing brain metastasis.”10
RIsING sTARs
EARLY CAREER RESEARCH
RESEARCHING bREAST CANCER: ADEDEJI ADEbAYO’S fOCUS ON HYPOXIA AND TUMOR MICROENVIRONMENTS
BY FAZILA RAJAB
Mr. Adedeji Adebayo received a bachelor’s degree in veterinary medicine and a master’s in veterinary pharmacology from the University of Ibadan, Nigeria. He is pursuing a PhD in biochemistry and molecular biology, focusing on cancer research from Indiana University School of Medicine, United States. He is also working as a part-time graduate assistant in his department. His research interests include biochemistry, cancer biology, breast cancer, tumor microenvironment, basic molecular biology techniques, and oxidative stress. In this interview, we asked Mr. Adebayo to discuss his research and his interest in oncology. We also asked him for advice for peer young career researchers, which can be equally valuable for anyone starting their unique career path.
Photo credit: Ousa Chea, Unsplash
OC Digest: What got you interested in oncology? What made you take a shift from veterinary medicine to oncology?
Adedeji Adebayo: I feel like I stumbled on oncology or cancer research because while in veterinary school in Nigeria, I had experience in cardiovascular research, mainly hypertension.
However, when I got to the United States, the professor I wanted to work with had to leave for a different school. So when he left, I had to shift my interests elsewhere. The next thing that came to mind was oncology research because Indiana University has an excellent cancer research focus.
So, it wasn’t difficult for me to decide to switch my interests from cardiovascular research to oncology research. And that’s what I’ve been doing for the past four, going to five years now.
OC Digest: How did you end up with research on breast cancer?
Adedeji Adebayo: Breast cancer came to me as a logical decision because of the prevalence of the disease among women and also considering how women of Black origin tend to be receiving the worst part of the disease, especially if you consider the death rate.
Although I have not had any personal experiences, when it comes to family members with the disease, I know a few people who have had breast cancer. So, it just seemed a logical decision for me to go into breast cancer research.
So, it’s mainly due to the fact that it’s highly prevalent among people, among women, where I’m from, which is in Nigeria. Also, the fact that if you compare breast cancer death rates between Black women and women of other races, then it’s entirely different. You can observe Black women being more at the receiving end of that compared to people of other races.
Mr. Adedeji Adebayo, photo courtesy of Adedeji Adebayo
OC Digest: Can you please tell us a little about your research project?
Adedeji Adebayo: Breast cancer, the tumor itself, where it comes from in the human body, is highly hypoxic in the sense that it is characterized by very low oxygen tensions.
Compared to the oxygen levels that these tumors and the cells that form them experience inside, which is as low as 0.5%, what oxygen we experience as human beings that we breathe in and out is a significantly higher amount, that is 21%. Despite that fact, the average cancer researcher does not really consider these oxygen levels.
So, most cancer researcher takes out these tumors, convert them into cells, and do every experiment within normal atmospheric oxygen conditions, exposing them to significantly higher amounts of oxygen than they actually experience where they come from in the human body. Our argument so far has been that by taking out these tumors and the cells that make them up from the human body, which has low oxygen levels, and exposing them to ambient oxygen levels that are significantly higher, you’re impacting their biology. By impacting their biology, you also impact their behavior and their response to specific targeted therapies and tumorigenesis.
In my research project, we have been examining how these different oxygen tensions impact signaling pathways relevant to developing therapies and how these cells respond to various targeted therapies.
By doing so, we have tried to develop different combination therapies to target signaling pathways that are differentially active under these low histologically relevant oxygen tensions compared to the ambient oxygen tensions that have much higher oxygen levels than they actually experience in vivo where they come from.
This particular research is the basis of my PhD dissertation.
OC Digest: How do you feel that you have impacted your field? What do you think are the long-term impacts of your research?
Adedeji Adebayo: So my hope is that with all this research, we’ll be able to improve how we approach preclinical cancer research, and that will probably even help us understand the biology of these tumors way better than we currently do, and also, in the process, with having more effective ways to develop targeted drugs that will more likely succeed in clinical trials. That is the way I think about it.
To some extent, we may have tried to change how people think about their approach to preclinical cancer research. I don’t know if it has significant effects, but I think we’ve shown a lot of compelling results to show that even if we don’t consider oxygen conditions as a factor that can actually confound our understanding of cancer biology, it at least brings it to people’s knowledge that even just oxygen tension alone is enough to impact what we understand about these cancers, not just breast cancer, but other cancer types. So, in the short term, we have tried to change people’s ideas regarding oxygen tension. Because, again, it is not an entirely new research area. Everybody knows that solid tumors have hypoxic oxygen levels in vivo. And if you take them out and put them in ambient oxygen tensions, it will be significantly higher.
But the truth is, if you are going to adopt the method we are adopting in our lab, which is to take care of these cells under more controlled oxygen tensions without ever exposing them to ambient oxygen, then it will require several logistical tools, which costs a lot of money. In that regard, convincing people that that is the way to go is not easy. But it is a logical point because if you are taking cells from a physiologic environment to an extraphysiologic environment, then the biology will be impacted, which will confound what you understand about their biology. I think people’s way of thinking about this might change to some extent in the short term.
OC Digest: Are there any specific findings in the field of cancer, in particular breast cancer, that you are excited about?
Adedeji Adebayo: Breast cancer research has evolved quite a lot. Perhaps it is one of the cancer types that has had a lot more progress in terms of developing therapies and trying to improve the conditions of people with the disease, which is very exciting to me. However, based on my research area, I am very interested in signaling pathways and how some of them can be targeted for therapy. That has been my biggest interest so far.
OC Digest: Why do you think mentorship is important in PhD career?
Adedeji Adebayo: The whole process of doing science in the first place is a challenging process. I do not think there is any textbook approach to doing research, but I feel like if people like us who are just studying, who are just budding researchers don’t have that guidance, at least at the beginning of the whole thing, it is going to be very, very easy to get discouraged and just drop out of PhD programs or stop the entire thing altogether.
I feel like mentorship really plays a significant role, especially from the get-go. And then it helps to keep pushing you forward.
And it is not just with the PhD alone. In life, it is always good to have a role model or mentor who can guide one through whatever challenges one has to go through. So, I feel like for that encouragement to continue to push, even in the face of challenges, good mentorship is required.
OC Digest: What is your motivation for research?
Adedeji Adebayo: For me, it is mainly the excitement of making new findings that could potentially improve the lives of people in the long run. I feel like the whole goal of doing research in the first place is trying to identify things that have not probably been identified before or at least try to improve your understanding of them.
The excitement of finding something new that could eventually improve people’s lives is enough motivation to keep going.
OC Digest: Are there any specific movements/ shifts in the direction of the field that you would like to see in the next five years?
Adedeji Adebayo: In the next five years, I want to see improvements in cancer therapy for improving people’s lives. I think the whole goal of doing this research in the first place is to try to develop something that will potentially work to improve people’s lives in the first place, and that’s what I want to see in five years. I want to see more progress in that direction.
OC Digest: What are the struggles that came with being an early career researcher? Describe the most challenging situation you have faced and how you overcame it.
Adedeji Adebayo: Well, initially, the first challenge I faced was inexperience. Having come from a veterinary background with experience in cardiovascular research, coming to do cancer research was a risk in a sense because it wasn’t something I was exposed to right from the beginning. But I think, to some extent, some of the classes I took at the start of the program really helped me understand some of the biology of cancer generally, not just breast cancer.
That was the initial challenge I faced, understanding the disease itself before I could start doing my research. However, as time passed, the next challenge I faced had more to do with my immigration status in this country than the actual research itself. Since I’m an international student, it meant I had more limited resources to potential grant funding. Of course, there are other means to get external funding, such as private foundations. However, when it comes to government funding, that is definitely limited for international students like me in the United States. Other than that, as an early career researcher, I’ve had the privilege of working with some of the best people in the field.
OC Digest: What advice would you give to your younger self and fellow researchers who want to start their career in research?
Adedeji Adebayo: You don’t have to have it all figured out from the beginning. Just take each day as it comes and keep doing your best.
Prepare your mind for challenges because research itself is not an easy process. You have to be resilient and be persistent. Just keep going and try to make it work.
Hanna TP, King WD, Thibodeau S, Jalink M, Paulin GA, Harvey-Jones E, O’Sullivan DE, Booth CM, Sullivan R, Aggarwal A. Mortality due to cancer treatment delay: systematic review and meta-analysis. bmj. 2020 Nov 4;371.
ONCOLOGY BREAKTHROUGHS
BREAST CANCER
HER2-positive advancement: The role of pyrotinib, a potent irreversible pan-HER inhibitor
Barrios C, Morelle A. Anti-HER2 Adjuvant Therapy. Breast Diseases: An Evidence-Based Pocket Guide. 2019:497-508.
Li SG, Li L. Targeted therapy in HER2-positive breast cancer. Biomedical reports. 2013 Jul 1;1(4):499-505.
Li Q, Guan X, Chen S, Yi Z, Lan B, Xing P, Fan Y, Wang J, Luo Y, Yuan P, Cai R. Safety, efficacy, and biomarker analysis of pyrotinib in combination with capecitabine in HER2-positive metastatic breast cancer patients: a phase I clinical trial. Clinical Cancer Research. 2019 Sep 1;25(17):5212-20.
Lin Y, Lin M, Zhang J, Wang B, Tao Z, Du Y, Zhang S, Cao J, Wang L, Hu X. Real-world data of pyrotinib-based therapy in metastatic HER2-positive breast cancer: promising efficacy in lapatinib-treated patients and in brain metastasis. Cancer Research and Treatment: Official Journal of Korean Cancer Association. 2020 Oct;52(4):1059.
Zhang J, Meng Y, Wang B, Wang L, Cao J, Tao Z, Li T, Yao W, Hu X. Dalpiciclib combined with pyrotinib and letrozole in women with HER2-positive, hormone receptor-positive metastatic breast cancer (LORDSHIPS): a phase Ib study. Frontiers in Oncology. 2022 Mar 7;12:775081.
LiX, YangC, WanH, ZhangG, FengJ, ZhangL, ChenX, ZhongD, LouL,TaoW,ZhangL. Discovery and development of pyrotinib: A novel irreversible EGFR/HER2 dual tyrosine kinase inhibitor with favorable safety profiles for the treatment of breast cancer. European Journal of Pharmaceutical Sciences. 2017 Dec 15;110:51-61.
Cao J, Teng Y, Li H, Zhang L, Ouyang Q, Xie W, Pan Y, Song Z, Ling X, Wu X, Xu J. Pyrotinib plus capecitabine for trastuzumab-resistant, HER2-positive advanced breast cancer (PICTURE): a single-arm, multicenter phase 2 trial. BMC medicine. 2023 Aug 9;21(1):300.
Ma F, Yan M, Li W, Ouyang Q, Tong Z, Teng Y, Wang Y, Wang S, Geng C, Luo T, Zhong J. Pyrotinib versus placebo in combination with trastuzumab and docetaxel as first line treatment in patients with HER2 positive metastatic breast cancer (PHILA): randomised, double blind, multicentre, phase 3 trial. bmj. 2023 Oct 31;383.
Xu B, Yan M, Ma F, Hu X, Feng J, Ouyang Q, Tong Z, Li H, Zhang Q, Sun T, Wang X. Pyrotinib plus capecitabine versus lapatinib plus capecitabine for the treatment of HER2-positive metastatic breast cancer (PHOEBE): a multicentre, open-label, randomised, controlled, phase 3 trial. The Lancet Oncology. 2021 Mar 1;22(3):351-60.
PRIMARY ANALYSIS OF THE PHASE 3 HER2CLIMB-02
Tucatinib and trastuzumab emtansine in HER2 +metastatic breast cancer
Ulrich L, Okines AF. Treating advanced unresectable or metastatic HER2-positive breast cancer: a spotlight on tucatinib. Breast Cancer: Targets and Therapy. 2021 May 26:361-81.
Garcia-Alvarez A, et al. Brain metastases in HER2-positive breast cancer: current and novel treatment strategies. Cancers. 2021 Jun 11;13(12):2927.
Murthy RK, et al. Tucatinib, trastuzumab, and capecitabine for HER2-positive metastatic breast cancer. New England Journal of Medicine. 2020 Feb 13;382(7):597-609.
Swain SM, et al. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): end-of-study results from a double-blind, randomised, placebo- controlled, phase 3 study. The Lancet Oncology. 2020 Apr 1;21(4):519-30.
Tukysa®. Mechanism of Action. Available at https://global.tukysa.com/mechanism-of-action. Accessed March 2024.
Greenblatt K, Khaddour K. Trastuzumab. [Updated 2022 Nov 28]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK532246/
Hurvitz S, et al. HER2CLIMB-02: Randomized, double-blind phase 3 trial of tucatinib and trastuzumab emtansine for previously treated HER2-positive metastatic breast cancer. Abstract GS1-10. SABCS. 2023 Dec 5.
ONCOLOGY COMPASS WELCOMES GILEAD AS NEW SPONSOR AND PARTNER
We are thrilled to welcome Gilead as the new Oncology Compass sponsor and partner. Gilead’s innovative contributions to oncology align perfectly with our mission to provide cutting-edge resources and support to the cancer care community. Together, we will advance the fight against cancer and enhance the lives of patients and their families. Welcome aboard, Gilead!
CONfERENCE CALENDAR
UPCOMING ONCOLOGY CONfERENCES THIS SUMMER
Oncology Compass Digest presents a selection of medical conferences happening this summer. Oncology Compass Calendar is the most comprehensive calendar of global oncology conferences.
Tumor type: Breast cancer GI cancers Genitourinary cancer Gynaecological cancers Head and Neck cancer Hematologic malignancies Liver cancer Lung cancer Neurological cancers Paediatric cancers Pancreatic cancer Rare cancers Skin cancer
Photo credit: Freepik.com
USER DATA & WEBSITE INSIGHTS
INSIGHTS FOR Q2 2024
ONCOLOGY COMPASS IS GLOBALLY BECOMING AN INCREASINGLY IMPORTANT PLATFORM FOR ONCOLOGISTS
17 Scientific Leaders
selected practice-relevant publications for lung, renal, gastro-esophageal, melanoma, multiple myeloma, prostate cancer and triple-negative breast cancer
395
ACTIVE users
GROWTH Q2‘23 VS Q2‘24
82%
TOP 3 FILTER CRITERIA:
MELANOMA
276
RCC
278
NSCLC
390
*Total number of clicks on filter criteria over time
Website Visitors
6,712
Pageviews
15,321
Sessions
8,035
Avg. Session
01:15
Pages per session
1.91
Avg. Session Duration per Returning User
6:30 min
Pages per Session per Returning User
5.14
USER DATA & WEBSITE INSIGHTS
VISITORS by DEVICES
device category
total visitors
pageviews
Desktop
4,127
10,748
Mobile
2,324
4,104
Tablet
121
218
TOP 10 COUNTRIES WHERE VISITORS COME FROM:
country
VISITORS
PAGEVIEWS
1. United Kingdom
1,342
1,409
2. United States
1,003
1,879
3. India
360
401
4. Switzerland
305
399
5. Poland
292
333
6. Italy
286
294
7. Germany
274
300
8. Ireland
196
200
9. Netherlands
187
219
10. Malta
140
149
The number of Visitors represents all visitors to Oncology Compass, both registered and non-registered users. The metrics for Users relate to the Registered Users data who have full access to the Oncology Compass platform.
VISITORS BY AGE / GENDER*
age
VISITORS
pageviews
1. 25-34
266
833
2. 35-44
232
567
3. 45-54
219
467
4. 18-24
193
496
5. 55-64
171
352
6. 65+
123
438
VISITORS BY GENDER *
62%
Female
38%
Male
* for the rest of visitors, the gender and age are unknown, they choose not to share it.
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