OBR Peer-Spectives

The approach to ESR1 and PIK3CA mutations in patients with hormone receptor–positive metastatic breast cancer continues to evolve. What role does circulating tumor DNA (ctDNA) play in treatment decisions? How should oncologists best approach patients with PIK3CA mutations who subsequently develop ESR1 mutations? VK Gadi, MD, PhD, professor and director of medical oncology and deputy director of the University of Illinois Cancer Center in Chicago, discusses with Robert A. Figlin, MD, the interim director of Cedars-Sinai Cancer in Los Angeles and Steven Spielberg Family Chair in Hematology-Oncology, how recent data are informing care for patients with comutations. “We now have at least one ESR1-targeting drug out there, and more to come,” Dr. Gadi explains. “Elacestrant is the drug I'm of course referencing, and that is used essentially like a single agent and works well for those patients. Even when they have, for example, PIK3CA mutations present.” He and Dr. Figlin consider when to act on ctDNA findings and potential future strategies. Dr. Gadi reported no relevant financial relationships. Dr. Figlin reported various financial relationships.

The last few years have seen “a remarkable change in both our approach and management of EGFR lung cancer,” says Shirish M. Gadgeel, MD, division head for hematology/oncology and associate director of Patient Experience and Clinical Care at the Henry Ford Cancer Institute in Detroit. He discusses key considerations for managing EGFR-mutated non-small cell lung cancer with Robert A. Figlin, MD, the interim director and Steven Spielberg Family Chair in Hematology-Oncology at Cedars-Sinai Cancer Center in Los Angeles. Dr. Gadgeel describes considerations for leptomeningeal metastases, important treatment toxicities, and exciting advances on the horizon. Dr. Gadgeel reported various financial relationships. Dr. Figlin reported various financial relationships.

When it comes to tackling fertility issues associated with cancer, “oncology clinicians are often reluctant to talk about this because it is really not our wheelhouse,” says Alison Wakoff Loren, MD, MSCE, chief of the Division of Hematology Oncology, director of Blood and Bone Marrow Transplantation, and the C. Willard Robinson Professor of Hematology-Oncology at Penn Medicine in Philadelphia. Dr. Loren and colleagues recently updated American Society of Clinical Oncology guidelines for fertility preservation in people with cancer. She discusses the key changes with Robert Figlin, MD, interim director at Cedars Sinai Cancer Center in Los Angeles and the Steven Spielberg Family Chair in Hematology-Oncology. “This is a really important topic that I think sometimes gets lost in the shuffle of the hecticness of a young person's cancer diagnosis,” Dr. Loren explains. Increased awareness among oncologists is a crucial step that can lead to faster referrals and interventions, she says. “You better be ready for the conversation,” she urges. Dr. Loren reported research funding from Equillium (Inst). Dr. Figlin reported various financial relationships.

“Second-line [estrogen receptor (ER)]-positive breast cancer has just become very complicated,” says Erika P. Hamilton, MD, the director of breast cancer and gynecologic cancer research at Sarah Cannon Research Institute in Nashville. She discusses the role of ESR1 mutations in selecting appropriate treatments and combination regimens for patients with ER-positive breast cancer who have disease progression with Robert A. Figlin, MD, the interim director of Cedars-Sinai Cancer in Los Angeles, and Steven Spielberg Family Chair in Hematology-Oncology. From when and how best to assess for ESR1 mutations to which trials inform current treatment options in clinic, Dr. Hamilton walks through the complex decision-making process. She also shares which trial readouts she is looking forward to seeing and how social media is influencing patient choices. Dr. Hamilton reported various financial relationships. Dr. Figlin reported various financial relationships.

Burnout among oncologists is a serious concern, and artificial intelligence (AI) represents a potential solution, says Debra Patt, MD, PhD, MBA, a practicing oncologist and breast cancer specialist in Austin, Texas, who also serves as the chair of the AI task force for the American Society of Clinical Oncology. Technological advances are poised to improve cancer care while reducing the documentation burden for oncologists, she tells Robert A. Figlin, MD, the interim director of Cedars-Sinai Cancer in Los Angeles, and Steven Spielberg Family Chair in Hematology-Oncology. Dr. Patt describes the various practical ways in which AI is already changing oncology clinics, but acknowledges a generational divide that will need to be bridged: “I would say that the youngest generation of oncologists that is coming out, they are digital natives. They have grown up with this,” she explains. But for those who have been in practice longer, “Change management for us looks a little bit different than it does for the younger generation of oncologists that just sort of do this naturally.” Dr. Patt reported no relevant financial disclosures. Dr. Figlin reported various financial relationships.

The standard approach of “7 + 3” chemotherapy in acute myeloid leukemia (AML) treatment has been in place for 50 years. But that may soon change, says Maximilian Stahl, MD, a member of the Adult Leukemia Group at the Dana-Farber Cancer Institute in Boston and a member of the faculty at Harvard University. “My prediction is that in 10 years, you will not see much 7 + 3 anymore. Maybe not even 10 years, maybe five years,” he tells Robert A. Figlin, MD, the interim director and Steven Spielberg Family Chair in Hematology-Oncology at the Cedars-Sinai Cancer Center in Los Angeles. Dr. Stahl describes how targeted therapies such as menin inhibitor revumenib (Revuforj), which was recently approved by the U.S. Food and Drug Administration, are transforming AML care. Although currently indicated for relapsed/refractory disease, trials are exploring frontline use. “Pretty much, if you can think of any combination treatment in your head, that is already an ongoing clinical trial,” Dr. Stahl explains. He outlines how targeted therapies have already changed practice and looks to what advances are likely in the near future. Dr. Stahl reported a consulting or advisory role with the Boston Consulting Group, Clinical Care Options, Curis Oncology, GlaxoSmithKline, Haymarket, Kymera, Novartis, and Sierra Oncology. Dr. Figlin reported various financial relationships.

Oncologist burnout and career dissatisfaction are a “huge problem,” says Robin T. Zon, MD, president of the American Society of Clinical Oncology (ASCO). Dr. Zon sits down with Robert A. Figlin, MD, the Steven Spielberg Family Chair in Hematology-Oncology at the Cedars-Sinai Cancer Center in Los Angeles, to discuss revelations from a recent ASCO report. “ASCO recognizes that if, in fact, we are going to accomplish our mission, we have to pay very close attention to what is happening to the workforce and the burnout that is associated with that,” Dr. Zon explains. She shares insights into common underlying causes and lays out a plan of attack for improvement. With an emphasis primarily on organizational, and not individual, reforms, Dr. Zon pledges that ASCO will remain focused on burnout and job dissatisfaction. “We are going to continue to have interventions. And we will continue to give voice to our members at all levels.” Dr. Zon reported various financial relationships. Dr. Figlin reported various financial relationships.

When it comes to end-of-life care for patients with cancer, “I think that there is a real deficit in our training,” says Nathan I. Cherny, MD, director of the Cancer Pain and Palliative Medicine Service at Shaare Zedek Medical Center in Jerusalem, Israel. Dr. Cherney and colleagues recently examined factors contributing to oncologists overtreating patients at the end of life. He discusses key findings and ways to address this continued problem with Robert A. Figlin, MD, the Steven Spielberg Family Chair in Hematology-Oncology at the Cedars-Sinai Cancer Center in Los Angeles. “When one reads practice guidelines, they never include a section of when further treatment is more likely to be harmful than helpful,” Dr. Cherny notes. “Unless it appears in every illness guideline, the message does not necessarily get through that this is something that is really important.” Dr. Cherny reported serving as a consultant for and owning stock in Canopy Care. Dr. Figlin reported various financial relationships.

Recent advances in hormone receptor–positive, HER2-negative metastatic breast cancer have led to questions about the timing of genetic testing and the optimal treatment choices for patients. “I, like many others, have changed my personal practice,” says Azka Ali, MD, a medical oncologist at the Cleveland Clinic Taussig Cancer Institute in Ohio. She and Robert A. Figlin, MD, the Steven Spielberg Family Chair in Hematology-Oncology at the Cedars-Sinai Cancer Center in Los Angeles, discuss what newly approved medications for patients with PIK3CA mutations mean for oncologists. “I think the breast cancer landscape is changing faster than we can all keep up with it,” Dr. Ali explains. She breaks down current genetic testing concerns and how she approaches treatment decisions that sometimes take place in a “data-free zone.” Dr. Ali reported no relevant financial disclosures. Dr. Figlin reported various financial relationships.

The European Society for Medical Oncology (ESMO) Resilience Task Force recently released recommendations intended to reduce burnout in oncology worldwide. One of the task force's members, Konstantinos Kamposioras, MD, PhD, a consultant in medical oncology at the Christie NHS Foundation Trust in Manchester in the United Kingdom, explains to Robert A. Figlin, MD, the Steven Spielberg Family Chair in Hematology-Oncology at Cedars-Sinai Cancer Center in Los Angeles, how those recommendations came to be and what institutions should do to help care for cancer care providers. They discuss differences between young oncologists and late-career specialists and consider solutions beyond those laid out in the ESMO guidance. “I'm wondering whether we have not done a good enough job having our primary care colleagues help us manage our cancer cases,” Dr. Figlin speculates. Dr. Kamposioras reported no relevant financial relationships. Dr. Figlin reported various financial relationships.

When it comes to the treatment of EGFR-mutated metastatic non-small cell lung cancer (NSCLC), osimertinib (Tagrisso) is an “old friend,” says Kamya Sankar, MD, assistant professor and co–medical director of the Thoracic Disease Research Group at Cedars-Sinai Cancer Center in Los Angeles. Recent approvals by the U.S. Food and Drug Administration have introduced several “new friends,” in the form of amivantamab (Rybrevant) and lazertinib (Lazcluze). Dr. Sankar talks with Robert A. Figlin, MD, the Steven Spielberg Family Chair in Hematology-Oncology also at Cedars-Sinai Cancer Center, about how to choose among osimertinib monotherapy, osimertinib plus chemotherapy, or amivantamab plus lazertinib. Without overall survival data available for all choices, Dr. Sankar explains how she and her patients decide which treatment is best, as well as how to consider sequential therapy after disease progression. Dr. Sankar reported no relevant financial relationships. Dr. Figlin reported various financial relationships.

“Cancer clinical research has been largely privatized,” explains Joseph Unger, PhD, MS, associate professor in the cancer prevention program at the Fred Hutchinson Cancer Center in Seattle. Dr. Unger and colleagues recently assessed patient enrollment in industry-sponsored and federally sponsored clinical trials. They found an 8:1 ratio favoring participation in research backed by industry. This raises significant concerns, he tells Robert A. Figlin, MD, the Steven Spielberg Family Chair in Hematology-Oncology at the Cedars-Sinai Cancer Center in Los Angeles. Dr. Unger explains what he sees as the root causes for the current imbalance, potential negative effects, and possible solutions for how to “rebalance the portfolio.” “I'm doing whatever I can to help illustrate what the issues are through my research,” he notes. Dr. Unger reported a consulting/advisory role with AstraZeneca and Loxo/Lilly. Dr. Figlin reported various financial relationships.

Treatment approaches for patients with hormone receptor (HR)-positive, HER2-negative breast cancer have rapidly evolved, thanks in part to data from three key studies. Erin Frances Cobain, MD, associate professor at the University of Michigan Rogel Cancer Center in Ann Arbor, explains how findings from the KEYNOTE-756, monarchE, and NATALEE clinical trials are influencing decision-making for these patients. She and Robert A. Figlin, MD, the Steven Spielberg Family Chair in Hematology-Oncology at the Cedars-Sinai Cancer Center in Los Angeles, discuss the evolving role of immunotherapy and how to choose between CDK4/6 inhibitors, given the recent U.S. Food and Drug Administration approval of adjuvant ribociclib for patients with early breast cancer who are at high risk for recurrence. Dr. Cobain acknowledges that these and other findings have led to “challenging discussions,” even if those conversations are ultimately beneficial. Dr. Cobain reported various financial relationships. Dr. Figlin reported various financial relationships.

Approvals of antibody-drug conjugates (ADCs) for metastatic breast cancer have introduced complex questions about HER2 expression. “It's certainly been a changing landscape, which has been confusing for all of us,” explains Ian Krop, MD, PhD, director of the clinical trials office, chief clinical research officer, and associate director for clinical sciences at Yale Cancer Center in New Haven, Connecticut. He and Robert A. Figlin, MD, the Steven Spielberg Family Chair in Hematology-Oncology at the Cedars-Sinai Cancer Center in Los Angeles, discuss how oncologists should best approach HER2 testing, ADC sequencing, and toxicity concerns. When it comes to answering key questions, “We're a little data-poor in some ways because this is such a rapidly evolving field,” Dr. Krop explains. He also considers what's next for ADCs in breast cancer, including the potential for those treatments to move into the curative early-disease setting. Dr. Krop reported various financial relationships.  Dr. Figlin reported various financial relationships.

Newly approved targeted therapies for patients with advanced hormone receptor (HR)-positive, HER2-negative breast cancer are changing care. “We have an abundance of opportunities, but challenges with having to choose the right opportunity at the right time,” says Robert A. Figlin, MD, the Steven Spielberg Family Chair in Hematology-Oncology at the Cedars-Sinai Cancer Center in Los Angeles. Dr. Figlin discusses how to navigate new options with Manali Bhave, MD, a breast medical oncologist and assistant professor at the Emory University School of Medicine in Atlanta. Dr. Bhave stresses that disease progression in breast cancer can't be addressed with a one-size-fits- all option. “Where do we go from here? I think it is largely dependent on clinical factors, patient comorbidities, and even biomarker status,” she explains. Dr. Bhave and Dr. Figlin discuss recent developments in targeted therapies and important challenges. “We've come a long way in treating metastatic HR-positive, HER2-negative breast cancer as more of a chronic disease,” she says. Dr. Bhave reported consulting fees from Lilly, Novartis, and AstraZeneca. Dr. Figlin reported various financial relationships.

Data on the use of durvalumab after chemoradiotherapy transformed the standard of care for patients with unresectable stage III non-small cell lung cancer (NSCLC). “This is a real practice-changing observation from the PACIFIC trial,” said Robert A. Figlin, MD, the Steven Spielberg Family Chair in Hematology-Oncology at the Cedars-Sinai Cancer Center in Los Angeles. He recently spoke with Meghan Mooradian, MD, an instructor at Harvard Medical School in Boston, about her team's recent research assessing the protocol established by the PACIFIC study. “We really are hoping for a cure,” she said in describing how she makes decisions related to the timing of durvalumab after chemoradiotherapy. Dr. Mooradian also addressed toxicity concerns and shared what she sees as lingering questions related to disease progression. “What should we really be using next?” she asked. Dr. Mooradian reported consulting or advisory roles with AstraZeneca, the Bristol Myers Squibb Foundation, Istari Oncology, Regeneron, and Xilio Therapeutics; and other relationships with Aptitude Health, Curio Science, DAVA Oncology, and OncLive/MJH Life Sciences. Dr. Figlin reported various financial relationships.

Results of the phase 3 LAURA clinical trial, presented at the 2024 American Society of Clinical Oncology Annual Meeting, showed that osimertinib significantly improves progression-free survival in patients with unresectable stage III EGFR-mutant non-small cell lung cancer (NSCLC) after chemoradiotherapy. “The benefits of osimertinib in this patient population when compared to placebo are just incredibly dramatic,” noted Robert A. Figlin, MD, the Steven Spielberg Family Chair in Hematology-Oncology at the Cedars-Sinai Cancer Center in Los Angeles. He spoke with lead study author Suresh S. Ramalingam, MD, the Roberto C. Goizueta Distinguished Chair for Cancer Research and the executive director at the Winship Cancer Institute of Emory University in Atlanta, about how oncologists should adjust their practice in the wake of these key findings. Dr. Ramalingam tackled questions about the optimal duration of osimertinib therapy, toxicity concerns, and notable benefits seen in the LAURA data. “Osimertinib reduced both intrathoracic progression and extrathoracic progression, particularly intracranial progression,” he noted. Dr. Ramalingam reported research funding from Amgen, AstraZeneca/MedImmune, Bristol Myers Squibb, Merck, Pfizer, and Takeda; travel, accommodations, and other expenses from AbbVie; and a relationship with the American Cancer Society. Dr. Figlin reported various financial relationships.

“I think the antibody-drug conjugates (ADCs) for physicians, and certainly patients too, are a little bit tough to wrap your head around,” says Erika P. Hamilton, MD, the director of breast cancer and gynecologic cancer research at Sarah Cannon Research Institute in Nashville. She discusses how TROP2-targeting ADCs currently fit into practice with Robert A. Figlin, MD, the Steven Spielberg Family Chair in Hematology-Oncology at the Cedars-Sinai Cancer Center in Los Angeles. From how to “choose the right patient for the right treatment at the right time” to important toxicity concerns, Dr. Hamilton shares her “elevator pitch” to patients when it comes to ADCs. “I think a very easy way to really talk about the activity at this point is just the fact that they're beating naked chemotherapy. So they are performing better than chemotherapy and, for the most part, comparing favorably in terms of side effects for patients as well.” Dr. Hamilton reported various financial relationships. Dr. Figlin reported various financial relationships.

Various survivorship guidelines for pediatric patients have been established, but “such guidelines do not exist in the adult world,” says Smita Bhatia, MD, MPH, director of the Institute for Cancer Outcomes and Survivorship and the Gay and Bew White Endowed Professor in Pediatric Oncology at the University of Alabama at Birmingham. With the number of adult cancer survivors rapidly rising, the time is now for major oncology societies to help create long-term health recommendations, she tells Robert A. Figlin, MD, the Steven Spielberg Family Chair in Hematology-Oncology at the Cedars-Sinai Cancer Center in Los Angeles. Dr. Bhatia and Dr. Figlin discuss the critical need to explore how recent advances in cancer care, such as targeted treatments and immunotherapies, may affect the future health of survivors. “If we don't start by constructing large cohorts and following them long term, we will have lost this opportunity that exists right now,” she explains. Dr. Bhatia is an Associate Editor for Journal of Clinical Oncology. Journal policy recused the author from having any role in the peer review of the manuscript discussed. Dr. Figlin reported various financial relationships.

Obstacles to “achieving a good, peaceful death” prevent many patients with cancer from the “dignified end” that they deserve, says Sunita Puri, MD, a palliative care physician and author. She and Robert A. Figlin, MD, the Steven Spielberg Family Chair in Hematology-Oncology at the Cedars-Sinai Cancer Center in Los Angeles, discuss frustrations and concerns about systemic failures in cancer care when it comes to death and dying. “We need to have this national dialogue around this topic,” argues Dr. Figlin. “It can't be under the covers, where we don't talk about it.” Dr. Puri reported no relevant financial disclosures. Dr. Figlin reported various financial relationships.

When it comes to the treatment of patients with relapsed/refractory chronic lymphocytic leukemia (CLL), "within the last eight months or so, we have had some exciting new events," says Daniel A. Ermann, MD, a hematologist-oncologist and assistant professor at the University of Utah Huntsman Cancer Institute in Salt Lake City. The U.S. Food and Drug Administration approved pirtobrutinib for previously treated CLL in December 2023 and approved the CAR-T therapy lisocabtagene ciloleucel for relapsed/refractory disease in March 2024. These new options for patients with unmet needs present "a difficult choice, and it is a little bit of a balance," Dr. Ermann explains. He discusses key considerations for treatment selection with Robert A. Figlin, MD, the Steven Spielberg Family Chair in Hematology-Oncology at the Cedars-Sinai Cancer Center in Los Angeles. 

Oncologists are struggling with the rising cancer mortality rate among millennial patients. "I think treating people our own age is definitely a trigger for a lot of people," said Sunita Puri, MD, a palliative-care physician and author. She spoke with Robert A. Figlin, MD, the Steven Spielberg Family Chair in Hematology-Oncology at the Cedars-Sinai Cancer Center in Los Angeles, about her recent article in The Atlantic, "The Silence Doctors Are Keeping About Millennial Deaths." Dr. Puri explained how age bias and other factors have led to challenges in providing the care that younger adults with terminal cancer both want and need. "We should be matching up medical treatment with the values of the patient. Younger people, in my experience, don't want to be protected from the truth," she said. Dr. Puri and Dr. Figlin discussed how certain training can help and which misperceptions should be challenged. "I think we're socialized as doctors to equate treatment, survival, benefit, and cure as our scope of care. But part of our care is absolutely seeing and hearing the person in front of us and understanding that person as a distinct individual."

Thoracic oncology was a major focus of the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, says Sandip P. Patel, MD, a medical oncologist and professor of medicine at the University of California San Diego. Practice-changing data were presented in both non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), Dr. Patel told Robert A. Figlin, MD, the Steven Spielberg Family Chair in Hematology-Oncology at the Cedars-Sinai Cancer Center in Los Angeles. 

The biggest data at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting in kidney cancer focused on biomarkers, says Brian I. Rini, MD, chief of clinical trials and the Ingram Professor of Cancer Research at the Vanderbilt-Ingram Cancer Center in Nashville. He discussed data from KEYNOTE-426 and several other key trials with Robert A. Figlin, MD, the Steven Spielberg Family Chair in Hematology-Oncology at the Cedars-Sinai Cancer Center in Los Angeles. 

Enfortumab vedotin plus pembrolizumab (EV/pembro) has “become the elephant in the room” when it comes to bladder cancer care, says Jonathan E. Rosenberg, MD, chief of genitourinary oncology service at Memorial Sloan Kettering Cancer Center in New York City. At the 2024 American Society of Clinical Oncology Annual Meeting, he discussed recent key advances in urothelial carcinoma treatment with Robert A. Figlin, MD, the Steven Spielberg Family Chair in Hematology-Oncology at the Cedars-Sinai Cancer Center in Los Angeles. 

Immunotherapy in “Hardest Stage” of NSCLC: Putting Recent Advances Into Practice Our host, Robert A. Figlin, MD, FACP, welcomes Melissa L. Johnson, MD, as a guest  

From ASCO 2024.   When it comes to the use of antibody-drug conjugates (ADCs) in breast cancer care, "we're past the inflection point," says Hope S. Rugo, MD, a breast cancer oncologist and professor of medicine in the Division of Hematology and Oncology at the University of California San Francisco Helen Diller Family Comprehensive Cancer Center. 

From ASCO 2024 The time it takes for a novel cancer therapy to go from investigational new drug application to U.S. Food and Drug Administration (FDA) approval is typically longer than a decade. “There has to be a better way,” says Bob T. Li, MD, PhD, MPH, a medical oncologist at Memorial Sloan Kettering Cancer Center in New York City and associate professor of medicine at Cornell University in Ithaca, New York. 

From ASCO 2024, Dr. Robert Figlin speaks with Dr. Samer Al Hadadi from University of Arkansas. "Very Important" Myeloma Data: ASCO Highlights, Smoldering Challenges, and More.

From ASCO 2024, Dr. Robert Figlin talks with Dr. Lauren Averett Byers from MD Anderson Cancer Center. Durvalumab's Benefit in SCLC "Beyond What We Might Have Expected"

From ASCO 2024 New Standard of Care in Melanoma? Neoadjuvant Immunotherapy Offers "Fantastic" Potential, Expert Says. Dr. Robert Figlin speaks with Dr. Christian Blank from Leiden University

From ASCO 2024, Dr. Robert Figlin welcomes Dr. Aditya Bardia from UCLA Health Jonsson Comprehensive Cancer Center. Should All Breast Cancer Patients Get T-DXd? "Results of DESTINY-Breast06 Do Suggest That"

Especially in rural areas, the growing oncologist shortage has “gotten to crisis level,” says Harsha Vyas, MD, president and founding partner of Cancer Center of Middle Georgia in Dublin. “We just don't have enough supply of medical oncologists/hematologists,” he tells Robert A. Figlin, MD, the Steven Spielberg Family Chair in Hematology-Oncology at the Cedars-Sinai Cancer Center in Los Angeles. Dr. Vyas puts forth his ideas for potential solutions, ranging from medical school debt repayment to congressional intervention. As Dr. Figlin notes, “we need to rethink” current approaches because there's a “storm” on the horizon and “we're all seeing it coming.” Dr. Vyas reported no relevant financial relationships. Dr. Figlin reported various financial relationships.

The development of noncovalent Bruton tyrosine kinase (BTK) inhibitors and other advances in chronic lymphocytic leukemia treatment signify that the “future is really exciting,” says Jennifer A. Woyach, MD, professor in the Division of Hematology at The Ohio State University in Columbus. Dr. Woyach speaks with Robert A. Figlin, MD, the Steven Spielberg Family Chair in Hematology-Oncology at the Cedars-Sinai Cancer Center in Los Angeles, about the potential of moving these new drugs into the frontline setting and other questions related to BTK inhibitor resistance. Dr. Woyach reported various financial relationships. Dr. Figlin reported various financial relationships.

Given recent data, how should oncologists choose a tyrosine kinase inhibitor (TKI) in patients with EGFR-mutated non-small cell lung cancer (NSCLC), and when should chemotherapy be introduced? “It's better to have choices than not,” explains Paul Bunn, MD, the Dudley Chair in Cancer Research at the University of Colorado in Aurora. Dr. Bunn discusses how recent trials influence treatment decisions in NSCLC with Robert A. Figlin, MD, the Steven Spielberg Family Chair in Hematology-Oncology at Cedars-Sinai Cancer Center in Los Angeles. Dr. Bunn stresses why molecular testing is so crucial and previews what additional findings are likely to further change practice in patients with EGFR-mutated NSCLC.

The treatment of biochemical recurrence in prostate cancer “is set for rapid development over the next few years,” says Edwin M. Posadas, MD, medical director of the Center for Uro-Oncology Research Excellence at the Samuel Oschin Comprehensive Cancer Center at Cedars-Sinai Medical Center. Data from the recent EMBARK trial have changed practice for the treatment of men with high-risk features. Dr. Posadas discusses these findings and related advances with Robert A. Figlin, MD, the Steven Spielberg Family Chair in Hematology-Oncology at Cedars-Sinai Cancer Center in Los Angeles. They also consider how the growing role of prostate-specific membrane antigen (PMSA) positron emission tomography (PET)-CT is “really impacting” care for patients with prostate cancer who have biochemical recurrence. Dr. Posadas explains why the best approach for patients with negative PSMA PET-CT results who have high-risk features remains “a point of great discussion.”

The U.S. Food and Drug Administration's recent accelerated approval of a tumor-infiltrating lymphocyte therapy in metastatic melanoma “is a real milestone,” after the approach was “pending for decades,” explains Jeffrey S. Weber, MD, PhD, deputy director at the NYU Langone Perlmutter Cancer Center. Dr. Weber, who was part of the team to first work with the treatment in the late 1980s, discusses the breakthrough with Robert A. Figlin, MD, the Steven Spielberg Family Chair in Hematology-Oncology at Cedars-Sinai Cancer Center in Los Angeles. They examine what this accelerated approval means for practice and consider the "incredibly expensive cost” associated with the treatment. They also consider the evolving role of high-dose interleukin-2 in this patient population.

Recent advances in metastatic urothelial carcinoma have meant that optimistic outcomes are “not as much of a fairytale,” says Robert Dreicer, MD, deputy director of the UVA Cancer Center and professor of medicine and urology at the University of Virginia School of Medicine in Charlottesville. From the recent approval of enfortumab vedotin plus pembrolizumab to other key findings recently presented at the American Society of Clinical Oncology Genitourinary Cancers Symposium, Dr. Dreicer discusses “paradigm-shifting” advances with Robert A. Figlin, MD, the Steven Spielberg Family Chair in Hematology-Oncology at Cedars-Sinai Cancer Center in Los Angeles. Dr. Dreicer explains the “deal-breaker” that renders one treatment strategy “a relative no-brainer” for certain patients, as well as what upcoming data are likely to change practice even more.

Recent approvals by the U.S. Food and Drug Administration (FDA) and findings from pivotal clinical trials have changed care for patients with breast cancer that has progressed after frontline hormone therapy. Ruth M. O'Regan, MD, chair of medicine and Charles H. Dewey Professor at the University of Rochester in New York, highlights which recent developments regarding second- and third-line treatments are most essential. She and Robert A. Figlin, MD, the Steven Spielberg Family Chair in Hematology-Oncology at Cedars-Sinai Cancer Center in Los Angeles, discuss which newly approved drugs are making a difference in patients with actionable mutations, as well as those without. Dr. O'Regan also details which soon-to-be reported studies she is awaiting in 2024.

Recent data on the use of immunotherapy and targeted treatments in patients with advanced non-small cell lung cancer (NSCLC) have introduced a myriad of questions. These include controversial topics and difficult decisions, like when to incorporate CTLA-4 inhibition and what patients can expect from immuno-oncology monotherapy in the metastatic setting. Edward B. Garon, MD, MS, professor in the department of medicine in hematology/oncology and director of the thoracic oncology program at the Jonsson Comprehensive Cancer Center at the University of California Los Angeles, discusses key challenges in NSCLC care with Robert A. Figlin, MD, the Steven Spielberg Family Chair in Hematology-Oncology at Cedars-Sinai Cancer Center in Los Angeles. From optimal strategies in second-line settings to promising clinical trials, Dr. Garon shares how he applies emerging information in practice.  

Belzutifan was recently approved by the U.S. Food and Drug Administration (FDA) for use in previously treated adults with advanced renal cell carcinoma. How should this drug best be incorporated into practice? Eric Jonasch, MD, professor in the Department of Genitourinary Medical Oncology at the University of Texas MD Anderson Cancer Center in Houston, and Robert A. Figlin, MD, the Steven Spielberg Family Chair in Hematology-Oncology at Cedars-Sinai Cancer Center in Los Angeles, discuss how the medication might be used in clinic. Dr. Jonasch also provides insight into the LITESPARK-005 study, which led to the FDA approval, as well as other ongoing trials that may further change the landscape of kidney cancer care.

CDK4/6 inhibitors “have really been a game changer” in metastatic breast cancer, according to Komal Jhaveri, MD, clinical director for early drug development and section head for endocrine therapy research at Memorial Sloan Kettering in New York City. However, optimal treatment strategies have been complicated by a lack of head-to-head trials. Dr. Jhaveri speaks with Robert A. Figlin, MD, the Steven Spielberg Family Chair in Hematology-Oncology at Cedars-Sinai Cancer Center in Los Angeles, about how “practice patterns have slightly shifted” despite challenges in assessing efficacy across regimens and approaches. Dr. Jhaveri also discusses her work on the INAVO120 study, which found a benefit in adding a PI3K inhibitor to the combination of CDK4/6 inhibitors and hormone therapy. The trial reported a “monstrously important clinical hazard ratio,” according to Dr. Figlin, and may help clarify best practices moving forward.

From compelling data presented at the San Antonio Breast Cancer Symposium to the recent U.S. Food and Drug Administration approval of capivasertib, 2023 saw numerous key advances in breast cancer care. Aditya Bardia, MD, MPH, director of the breast cancer research program at Massachusetts General Hospital and associate professor at Harvard Medical School in Boston, and Robert A. Figlin, MD, the Steven Spielberg Family Chair in hematology-oncology at Cedars-Sinai Cancer Center in Los Angeles, discuss how several notable developments are already impacting practice. Dr. Bardia explains why genotyping is essential, provided it is available and affordable, and what recent changes have meant for the “roadmap” he presents to patients with metastatic disease. He also considers what 2024 may have on tap for this rapidly changing field.

From the use of prostate-specific membrane antigen (PSMA) positron-emission tomography (PET) to advancements in targeted treatments, prostate cancer care is quickly evolving. Edwin M. Posadas, MD, director of the Experimental Therapeutics Program and director of the Center for Urologic Oncology Research Excellence at Cedars-Sinai in Los Angeles, speaks with Robert A. Figlin, MD, the Steven Spielberg Family Chair in Hematology-Oncology at Cedars-Sinai, about how he is already implementing promising new data into practice. Although Dr. Posadas notes that although immunotherapy approaches in prostate cancer have been “a bit of a disappointment” so far, he sees “a lot of exciting research going on.” He explains why he doesn't “like to wait” when expanding his therapeutic armamentarium and why he prefers to be “proactive rather than reactive” when it comes to molecular profiling and other approaches.

Results of the recent EMBARK study show that both enzalutamide plus leuprolide and enzalutamide monotherapy significantly improved metastasis-free survival compared with leuprolide alone in patients with prostate cancer who have high-risk biochemical recurrence. Lead author Stephen Freedland, MD, associate director for education and training and director of the Center for Integrated Research in Cancer and Lifestyle at Cedars-Sinai Cancer Center in Los Angeles, speaks with Robert A. Figlin, MD, the Steven Spielberg Family Chair in Hematology-Oncology at Cedars-Sinai, about how these findings should be applied in practice. Although the data represent a significant advance, Dr. Freedland suggests even more progress ahead, asking "This is the new standard, but for those [who] are really high-risk, how can we do even better?”

Studies involving high-risk, early-stage ER-positive breast cancer are among the most eagerly anticipated at this year's San Antonio Breast Cancer Symposium (SABCS), to be held Dec. 5-9. Virginia Kaklamani, MD, professor of medicine in the division of hematology and medical oncology at the University of Texas Health Sciences Center San Antonio and leader of the breast cancer program at the Mays Cancer Center, discusses which data she thinks has the best chance of changing practice soon. She also speaks with Bob Figlin, MD, the Steven Spielberg Family Chair in hematology-oncology at Cedars-Sinai Cancer Center in Los Angeles, about key research into HER2-positive disease, brain metastases, and local therapy to watch for at this year's conference.

Last month, a U.S. Food and Drug Administration (FDA) Oncologic Drugs Advisory Committee (ODAC) determined that progression-free survival (PFS) could not be reliably interpreted in a confirmatory clinical trial for sotorasib (Lumakras) used to treat KRAS G12C–mutated locally advanced or metastatic non-small cell lung cancer (NSCLC). Ravi A. Madan, MD, senior clinician at the National Cancer Institute's Center for Cancer Research and chair of the ODAC, speaks with Robert A. Figlin, MD, the Steven Spielberg Family Chair in Hematology-Oncology at Cedars-Sinai Cancer Center in Los Angeles, about broader implications from the 2-10 vote against the sotorasib data. They discuss the specific rationale behind the decision, as well as what this means for clinical practice in the short term and big picture solutions to help improve future trials.

How should results of the FLAURA2 clinical trial be applied in practice? The study examined the use of osimertinib plus chemotherapy in the first-line treatment of EGFR-mutated advanced non-small cell lung cancer (NSCLC) compared with osimertinib alone and found that progression-free survival was significantly improved with the combination treatment. Pasi A. Jänne, MD, PhD, director of three cancer centers at the Dana-Farber Cancer Institute in Boston, including the Lowe Center for Thoracic Oncology, shares his team's findings with Bob Figlin, MD, the Steven Spielberg Family Chair in hematology-oncology at Cedars-Sinai Cancer Center in Los Angeles. They discuss toxicity concerns, best practices for treatment assessment, and how to identify patients for whom the new strategy may yield the best results.

“Therapies are improving dramatically” in mantle cell lymphoma (MCL), according to Michael Wang, MD, professor in the department of lymphoma/myeloma, division of cancer medicine at the University of Texas MD Anderson Cancer Center in Houston. Dr. Wang presented updates on major advances in MCL at the recent Society of Hematologic Oncology (SOHO) annual meeting. Here, he speaks with Bob Figlin, MD, the Steven Spielberg family chair in hematology-oncology at Cedars-Sinai Cancer Center in Los Angeles, about which promising regimens from recent studies are most appropriate for certain age groups. Dr. Wang and Dr. Figlin also discuss common challenges when approaching newly diagnosed patients, as well as how to process the “explosion” of new information in MCL.

Recent advances have provided new options for when and how best to treat patients with chronic lymphocytic leukemia (CLL). Trials of combination strategies have shown promise in providing patients the potential for unmaintained remissions. Marco Ruella, MD, an assistant professor of medicine in hematology-oncology at the Perlman School of Medicine at the University of Pennsylvania and scientific director of the lymphoma program, speaks with Robert Figlin, MD, the Steven Spielberg Family Chair in hematology-oncology at Cedars-Sinai Cancer Center in Los Angeles, about the current state of CLL care and what changes are likely in the near future. Although satisfied in many ways with recent progress, Dr. Ruella argues in favor of moving past simply “maintaining the disease at long-term” and, instead, pushing for a cure.   Dr. Ruella reports relationships with AbClon, BMS, Bayer, NanoString, and UPenn/Novartis.   Dr. Figlin has reported relationships with numerous companies.

The World Conference on Lung Cancer (World Lung) will be held in Singapore, September 9–12. The current president of International Association for the Study of Lung Cancer (IASLC), Heather A. Wakelee, MD, division chief of medical oncology at the Stanford Cancer Institute in California, shares which presentations and findings she is most looking forward to at this year's event. She speaks with Robert Figlin, MD, the Steven Spielberg Family Chair in hematology-oncology at Cedars-Sinai Cancer Center in Los Angeles, about steps being taken to ensure that key information from the conference is communicated quickly, clearly, and effectively to community oncologists around the world. They also discuss specific issues that will be addressed in Singapore, including a focus on lung cancer screening and why overcoming obstacles to more widespread uptake is crucial.