ASCO 2024 Interview: Luis E. Raez - European Medical Journal

ASCO 2024 Interview: Luis E. Raez

7 Mins
Oncology

Luis E. Raez | Medical Director and Chief Scientific Officer at Memorial Cancer Institute/Memorial Healthcare System, Hollywood, Florida, USA, Past President Florida Society of Clinical Oncology (FLASCO)

Citation: Oncol AMJ. 2024; https://doi.org/10.33590/oncolamj/LFLE2986.

Can you share some insights on the latest advancements in hematology and oncology that are currently being implemented at the Memorial Cancer Institute?

At Memorial Cancer Institute we partner with the Lee Moffitt Cancer Center, the number one cancer center in Florida. We have nine Moffit doctors working here with the latest technology in hematologic malignancies, including chimeric antigen receptor T (CAR-T) cells, tumor-infiltrating lymphocytes (TILs), and other new therapies. Hematological malignancies are shifting to what we call cellular therapy, which works from leukemia to myeloma and lymphoma. As a result, in South Florida, we not only provide state-of-the-art CAR-T cell, autologous, and allogeneic cell therapy but we also hold new and promissory clinical trials. The Moffitt Malignant Hematology & Cellular Therapy at Memorial Healthcare System is what you could call a satellite cancer center because these Moffit doctors live and practice in Miami and Broward counties, taking care of all the hematology malignancy needs in the tri county area.

In solid tumors, we do a lot of clinical research. Memorial Cancer Institute has participated in the development of several FDA-approved drugs like larotrectinib for NTRK gene fusions that are present in more than 18 different tumor types, and selpercatinib in RET fusions in lung and thyroid cancers, we were the only center in South Florida that were able to offer our patients access to these agents. We have done many clinical trials with immunotherapy: pembrolizumab, atezolizumab, nivolumab, and other immunotherapeutic agents. For us, it’s essential to be involved in clinical trials because we sometimes offer our patients the availability of new agents not available in the market 2 or 3 years before FDA approval. That is  tremendously important, especially when caring for patients with cancer who are often limited in options.

Given your extensive experience, what do you consider to be the most significant breakthrough in cancer treatment in recent years, and how has it impacted patient care?

In recent years, two of the most notable breakthroughs in cancer treatment are precision medicine and immunotherapy.

Precision medicine has made significant strides by allowing us to use molecular and genetic testing to determine the specific genetic or genomic profile of a patient’s cancer. Based on the genes involved in oncogenesis, we can now select targeted therapies. For example, in lung cancer, ten identified genetic aberrations that can be targeted with FDA-approved drugs. These tyrosine kinase inhibitors (TKIs), which are small oral molecules designed to attack specific cancer mutations, have a success rate of approximately 60–70% of the time. However, even with these 10 targets in lung cancer, we currently address the cancer needs of only about 30% of patients. This highlights the need to continue discovering new genes and genetic mutations to develop additional targeted therapies, to eventually cover most, if not all, lung cancer cases.

On the other hand, immunotherapy has transformed treatment approaches by targeting the immune system. Over 10 years ago, it was discovered that the immune system has checkpoints that allow cancers to proliferate unchecked. Immunotherapy involves using antibodies to stimulate the immune system to recognize and fight cancer cells. This approach has been particularly successful, starting with melanoma and expanding to more than 35 cancers. Despite this progress, we need to do more, we are still working to extend immunotherapy to earlier stages of cancer, such as Stages I, II, and III. A compelling example of immunotherapy’s success is the case of President Jimmy Carter, who was treated with pembrolizumab for advanced melanoma after a standard of care failure to control the tumor and experienced a cure. This demonstrates the potential of immunotherapy to achieve cures even in severe cases.

In summary, precision medicine and immunotherapy are the two most significant breakthroughs in recent cancer treatment. Precision medicine continues to advance with the identification of new genetic targets, while immunotherapy is expanding its effectiveness across a broader range of cancers and stages. There is still much work to be done, but these innovations have already made a profound impact on patient care.

How does your role as Chief Scientific Officer influence the strategic direction and research priorities at the Memorial Cancer Institute?

I’m responsible for shaping our strategic direction and research priorities at Memorial Cancer Institute. Given the increasing demand for cancer care, driven by a growing population in South Florida, our focus remains on addressing both immediate patient needs and advancing scientific progress.

Our cancer center is committed to enhancing patient outcomes beyond the current 60–65% cure rate reported by the National Cancer Institute (NCI). This commitment drives our emphasis on cutting-edge research and innovation. We continuously strive to expand our portfolio of clinical trials and seek partnerships with industry leaders to develop and evaluate new therapeutic agents. This approach is crucial because many of our patients face urgent needs that may not align with traditional drug approval timelines. By facilitating early access to experimental treatments, we offer hope to those who may otherwise have limited options.

Our role as one of the top cancer centers in the state is to not only provide exceptional care but also to push the boundaries of scientific knowledge. This dual focus on clinical and research excellence ensures that we remain at the forefront of cancer treatment, striving to turn groundbreaking discoveries into tangible benefits for our patients. Our research enterprise is significantly strengthened by our partnerships with Lee Moffitt Cancer Center, which brings over 40 healthcare professionals who live and work alongside us in Broward County. Additionally, our collaboration with Florida Atlantic University (FAU) provides vital expertise in the basic sciences, with dozens of cancer researchers working together with Memorial in the fight against cancer. As a result of these collaborations, we have earned the prestigious designation by the Florida Department of Health as one of only six Cancer Centers of Excellence in Florida.

What are some of the challenges you face in integrating cutting-edge scientific research into clinical practice, and how do you address these challenges?

One of the primary challenges in integrating cutting-edge scientific research into clinical practice is the time and effort required from both doctors and patients. When introducing a new drug or clinical trial, we face the significant task of thoroughly explaining the treatment to patients, who must then consent to participate. This process involves additional tests, such as specialized labs, ECGs, and CT scans, not only to evaluate the new drug but also to ensure patient safety. These extra requirements can be demanding for patients, who may experience delays or cancellations due to their medical conditions. For doctors, it means managing an increased workload and ensuring comprehensive patient monitoring.

Furthermore, access to clinical trials can be limited. Not all patients have the resources to travel or stay in locations where trials are conducted. This creates a cancer disparity, as trials often recruit from more affluent populations, which may not represent the broader, diverse patient base we see in community clinical settings. Many patients, including those from underserved communities or those without adequate insurance, cannot afford or are unable to participate in these trials.

The lack of diversity in clinical trials can lead to results that may not fully reflect real-world outcomes. This disconnect can be problematic when new treatments are introduced into the community setting, as they may not perform as expected based on trial data alone from a major academic center with no diversity in its population. The FDA is now emphasizing the need for more diverse and representative clinical trials to ensure that new treatments are evaluated in settings that more accurately reflect the patient population. Addressing these challenges requires a concerted effort to make trials more accessible and inclusive, and to ensure that research outcomes apply to a wider range of patients.

Can you discuss any ongoing or upcoming clinical trials at the Memorial Cancer Institute that you are particularly excited about?

At Memorial Cancer Institute, we currently offer cellular therapy using CAR-T cells for hematological malignancies as a standard of care. We are excited to announce our forthcoming clinical trial, which will be the first to investigate CAR-T cells for treating solid tumors. This study is particularly innovative because CAR-T cells have not yet been approved for use in solid tumors, such as those in lung, head and neck, and breast cancers. We are at the forefront of exploring their potential in these areas, working closely with our sponsor to evaluate the efficacy and role of CAR-T cells in these solid tumor types.

Additionally, we are researching a rare genetic aberration known as NRG1, which, although infrequent, may be found in over 15 different types of tumors. This makes our research especially promising, as finding effective treatments for such a diverse range of cancers could offer new hope to many patients. We are currently the only center in Florida conducting a trial specifically for this genetic aberration, and we are hopeful that patients from other cities will also participate.

For those who might not be familiar, can you explain what the Best of ASCO® symposium is and its significance in the field of oncology?

The American Society of Clinical Oncology (ASCO) is the largest professional cancer society in the United States, encompassing a community of 45,000 medical oncologists, surgeons, and radiation oncologists. Each year, ASCO hosts a massive annual meeting in Chicago, attracting all 45,000 attendees. Given the scale of this event, navigating it can be quite challenging. To address this, ASCO established the Best of ASCO® meetings as satellite events that follow the annual meeting.

Eight years ago, we brought this initiative to South Florida, and at the Memorial Cancer Institute, we are proud to host the franchise for South Florida for ASCO. Each July, we organize a 2-day meeting that reviews and highlights the key presentations and discoveries from the Chicago conference attended by more than 300 people.

With approximately 2,500 presentations at the annual meeting, our goal is to showcase around 70–80 of the most impactful ones. This allows doctors, nurses, and other healthcare providers who couldn’t attend the main event to stay informed about the latest advancements and breakthroughs in oncology.

Can you highlight a few key findings from the meeting that you believe will significantly impact clinical practice?

During the ASCO plenary session, we were fortunate to hear about two groundbreaking abstracts related to lung cancer. Small cell lung cancer, though only comprising about 13% of all lung cancers, still represents a significant number of Americans, approximately 25,000 individuals. Historically, our treatment approach involved chemotherapy and radiation, which unfortunately only cured about 25% of patients. This standard of care has persisted for over three decades. Increasing chemotherapy doses did not improve outcomes; it only resulted in greater patient discomfort without enhancing cure rates. Administering immunotherapy for 2 years after initial treatment has significantly improved patient survival rates (ADRIATIC studyl.1 This breakthrough is like hitting a home run, and we are eager to implement this approach nationwide as it holds the potential to save many lives.

Non-small cell lung cancer locally advanced (Stage III), was previously treated with chemoradiation. Over the past 4–5 years, immunotherapy has become the standard of care, significantly prolonging survival. People with genetic mutations, such as the common epidermal growth factor receptor (EGFR) mutation that is present in 15% of Americans, typically receive chemoradiation therapy only, not candidates for immunotherapy. However, there was no evidence that this treatment alone could extend survival in a significant group of patients as we have seen for years. Remarkably, this year, it was demonstrated that after chemoradiation, which is the standard of care for these patients, instead of discontinuing treatment, administering the appropriate oral medication, osimertinib for those with the EGFR mutation (LAURA study),2 can significantly increase progression-free survival from 8–9 months to as long as 40 months. The benefit of adding osimertinib is substantial.

These examples highlight the remarkable progress we are making and the tremendous benefits these new treatments offer to our patients.

During the symposium, were there any sessions or presentations that you found especially impactful or surprising? If so, could you elaborate on why?

In melanoma, although it’s rarer than breast, prostate, or lung cancers, significant advances are being made. For example, treatments targeting the BRAF genetic mutation include oral agents and immunotherapy. However, these treatments are often effective only temporarily. The BRAF mutation is notable because it appears in over 15 cancers across both children and adults, highlighting a crossover between different scientific fields. This has led to new cancer drugs that benefit both age groups.

Historically, patients would respond to either tyrosine kinase inhibitors (TKIs) or immunotherapy, but not both. In melanoma, where the BRAF mutation was first identified, there’s evidence that combining both treatments can be beneficial, though it can be quite toxic to do at the same time. Some studies suggest starting with oral TKIs followed by immunotherapy or vice versa. Currently, using immunotherapy before TKIs appears to be the most effective strategy to prolong survival with acceptable toxicity. These insights into melanoma are likely to influence treatment approaches for other cancers with the BRAF mutation.

How do you plan to integrate the insights and discoveries presented at the Best of ASCO® 2024 into your practice at Memorial Cancer Institute?

ASCO meetings play a crucial role nationwide. When a breakthrough is presented at ASCO, it’s important to adopt it as quickly as possible. For instance, the recent discovery that immunotherapy consolidation after chemoradiation for small cell lung cancer1 can extend the lives of some patients is a significant advancement. While the FDA is usually aware of such breakthroughs, they often don’t wait for scientific presentations to act. The FDA typically engages with the sponsor ahead of these major meetings, so we often see FDA approval shortly after these presentations.

Additionally, I am keen to implement new treatments for my patients, but it’s frustrating when insurance does not cover them. Despite these challenges, attending these meetings is essential because they help us stay updated on new procedures and treatments that can benefit patients.

Not every meeting will feature a groundbreaking discovery; sometimes it’s about a new drug that, while offering the same effectiveness as existing treatments, is less toxic. Such advancements improve patients’ quality of life. Even if the innovations aren’t groundbreaking, they still provide clear benefits to patients, underscoring the importance of participating in these meetings and staying current.

References
AstraZeneca. Study of Durvalumab + Tremelimumab, Durvalumab, and Placebo in Limited Stage Small-Cell Lung Cancer in Patients Who Have Not Progressed Following Concurrent Chemoradiation Therapy (ADRIATIC). NCT03703297. https://clinicaltrials.gov/study/NCT03703297. AstraZeneca. A Global Study to Assess the Effects of Osimertinib Following Chemoradiation in Patients With Stage III Unresectable Non-small Cell Lung Cancer (LAURA). NCT03521154. https://clinicaltrials.gov/study/NCT03521154.

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