Panelists discuss how treatment selection between lorlatinib and alectinib for ALK-positive non–small cell lung cancer should consider both efficacy data favoring lorlatinib and patient-specific factors like neuropsychiatric history or cardiovascular comorbidities that might favor alectinib.
Panelists discuss how extended follow-up from CARTITUDE-1 shows continued overall survival benefit with minimal new safety concerns, reinforcing the durability and safety of cell therapy.
Panelists discuss real-world evidence comparing immunotherapy combinations for metastatic melanoma, highlighting retrospective analyses showing similar efficacy between nivolumab plus relatlimab and nivolumab plus ipilimumab, while emphasizing the relatlimab-based regimen’s lower toxicity and the need for individualized treatment decisions in patients who fall outside typical clinical trial populations.
Panelists discuss how they approach the treatment journey by prioritizing early IDH mutation detection, coordinating multidisciplinary teams for maximal safe resection, and utilizing advanced surgical techniques to optimize outcomes while preserving neurologic function.
Panelists discuss how the 2021 WHO classification has fundamentally shifted glioma diagnosis from histologic appearance to molecular markers, particularly IDH mutation status, which now determines treatment strategies and prognosis.
Panelists discuss how a 48-year-old fitness instructor with ALK-rearranged stage IV lung cancer and bone metastases was successfully treated with alectinib, experiencing manageable adverse effects while returning to modified teaching activities.
Panelists discuss how some patients in CARTITUDE-1 maintained stringent complete remission for more than 5 years without further treatment, potentially redefining the concept of cure in myeloma.
Panelists discuss the prioritization of immunotherapy over targeted therapy for BRAF-mutant metastatic melanoma, highlighting updated RELATIVITY-047 data supporting nivolumab plus relatlimab for its durable efficacy and favorable toxicity profile, and emphasizing the importance of individualized treatment selection based on evolving evidence, patient goals, and comparative analyses of combination regimens.
Panelists discuss how the OPTEC trial and other studies demonstrate that outpatient teclistamab administration with prophylactic tocilizumab is feasible and safe, with no cytokine release syndrome (CRS) events reported in community settings, while acknowledging that Risk Evaluation and Mitigation Strategies (REMS) requirements remain a significant barrier to broader community adoption despite the reality that most CRS is now grade 1-2 and manageable with supportive care, suggesting the field needs to follow lymphoma’s example of bispecifics without REMS restrictions.
An ongoing phase 1 trial seeks to prove XmAb819 as an effective treatment and ENPP3 as a plausible target in patients with relapsed or refractory RCC.
“The therapy is designed to prevent CAR T-cell inactivation and to restore the antitumor immunity of the white blood cells that have gotten through the tumor,” said Wayne A. Marasco, MD, PhD.
Panelists discuss how a 69-year-old woman with newly diagnosed EGFR-mutant mNSCLC and symptomatic brain metastases requires immediate multidisciplinary care including steroids, radiation oncology consultation, and potential hospitalization, with treatment approach favoring stereotactic radiosurgery for dominant lesions followed by combination therapy like FLAURA2, while emphasizing that asymptomatic patients might allow for initial tyrosine kinase inhibitor treatment with close monitoring before considering radiation to potentially reduce treatment field and minimize long-term neurotoxicity.
Panelists discuss how treatment decisions for a 45-year-old avid rock climber with EGFR-mutant mNSCLC and liver metastases must balance his need to maintain work and income with optimal cancer care, considering his travel requirements and quality of life preferences, while acknowledging that the presence of TP53 comutations would suggest more aggressive disease requiring consideration of combination therapy despite potential lifestyle impacts, and that MET overexpression in the second-line setting offers targeted options like tepotinib or capmatinib.
Panelists discuss how retreatment with platinum doublet chemotherapy after FLAURA2 progression is considered as a potential option when patients have been chemotherapy-free for at least 6 months (using platinum sensitivity principles), with clinicians preferring to exhaust all targeted therapies and considering newer agents like datopotamab deruxtecan first, while acknowledging that retreatment with chemotherapy represents a safety net option for patients who remain fit enough to tolerate it.
Panelists discuss how the decision to continue targeted TKI therapy in the second-line setting depends on multiple factors including intracranial progression status, extent of disease progression, prior radiation therapy, and individual patient circumstances, with clinicians preferring to continue TKI for isolated CNS progression that can be managed with radiation while switching to different regimens for widespread progression or recurrent intracranial disease after prior radiation.
Panelists discuss how their approach to second-line treatment decision-making prioritizes biomarker-directed therapies over biomarker-agnostic approaches, with clinicians preferring to exhaust all targeted therapy options based on molecular alterations identified through rebiopsy and plasma testing before moving to tumor-agnostic treatments like datopotamab deruxtecan or docetaxel, emphasizing the importance of molecular matching for optimal patient outcomes.
Panelists discuss how tissue vs plasma biopsy strategies after first disease progression typically prioritize liquid biopsy due to convenience and improving technology, with tissue rebiopsy reserved for cases of rapid progression in multiple sites, clinical suspicion of transformation or resistance mechanisms not detected on liquid biopsy, or when oligoprogressive disease cannot be managed with local therapy, emphasizing that rebiopsy decisions should be based on whether results will change management.
Panelists discuss how the choice of frontline therapy influences future treatment options by requiring strategic planning for progression, with emphasis on using radiation for oligoprogressive disease to continue effective treatments, repeating genomic testing to assess resistance patterns, considering clinical trials, and utilizing multidisciplinary approaches including surgery for oligoresidual disease to potentially achieve curative outcomes in selected patients.
Panelists discuss how multidisciplinary collaboration with subspecialists, particularly dermatologists, is essential for managing cutaneous and other treatment toxicities associated with combination therapies like amivantamab and tyrosine kinase inhibitors, as dermatologists have become increasingly familiar with oncology-related toxicities and can provide specialized interventions when standard preventive measures fail, with access to academic medical centers offering additional expertise for complex cases.
Panelists discuss how the availability of subcutaneous amivantamab could be a game changer for clinical practice by lowering the threshold for using amivantamab plus lazertinib combination therapy, as it would decrease infusion-related reactions, reduce VTE risk, improve infusion center efficiency, and make the regimen more appealing to patients by offering an injection plus pill vs multiple intravenous chemotherapy medications plus pill.
Panelists discuss how toxicity discussions with patients must emphasize different adverse effects for each combination therapy, with osimertinib plus chemotherapy requiring focus on fatigue, cytopenias, and dermatologic toxicity, while amivantamab plus lazertinib requires discussion of infusion reactions, venous thromboembolism prophylaxis, and skin toxicities, though they acknowledge that complex prophylactic regimens can be challenging for patients with lower health literacy and may involve significant financial burden.
Panelists discuss how combination therapies create additional time and financial burdens compared with osimertinib monotherapy, with treatment requiring more frequent visits (every 3 weeks for FLAURA2, weekly then biweekly for amivantamab), and while some clinicians follow trial protocols to continue maintenance pemetrexed, others have a lower threshold to discontinue it to reduce time toxicity and improve quality of life, balancing patient preferences with potential treatment benefits.
Panelists discuss how the projected 1-year overall survival benefit from the amivantamab plus lazertinib combination in the MARIPOSA trial represents impressive and meaningful progress for patients with incurable disease, with the hazard ratio of 0.75 being a significant deciding factor for many patients, though they acknowledge the complexity of interpreting this benefit given the lack of crossover in the trial and uncertainty about optimal sequencing strategies.
Panelists discuss how maintaining quality of life must be balanced with efficacy in metastatic lung cancer patients, emphasizing the importance of early intervention for adverse events through patient education, frequent follow-up visits (including day 8 and day 15 visits), close monitoring with laboratory checks, and proactive communication via nursing and pharmacy teams to ensure patients can stay on therapy longer and derive maximum clinical benefit.
Panelists discuss how resistance mechanisms influence frontline therapy selection, with clinicians considering comutational status, brain and liver involvement, and disease burden when choosing combination therapies, while acknowledging the chess-like strategic thinking required to balance optimal progression-free survival with future treatment options, especially given that 25% to 30% of patients may not receive second-line therapy.
Panelists discuss how choosing between the 2 combination therapies (osimertinib plus chemotherapy vs amivantamab plus lazertinib) involves considerations of familiarity and comfort level, with many clinicians favoring the more familiar chemotherapy plus osimertinib approach while acknowledging that having different mechanistic options provides valuable sequencing flexibility for future treatment decisions.
Panelists discuss how patient preferences for EGFR-mutant mNSCLC treatment vary widely based on medical literacy, information-seeking behavior, and prior experiences, with clinicians emphasizing the importance of shared decision-making, understanding patients’ reasoning behind their preferences, and meeting patients where they are in their knowledge and comfort level to formulate treatment plans that align with their goals of care.
Ongoing studies aim to combine base immunotherapy regimens with novel agents to potentially improve outcomes among patients with kidney cancer.
Investigators have found a way to reduce liver and biliary toxicity when targeting the molecule CAIX in patients with clear cell renal cell carcinoma.
Panelists discuss how treatment decisions between osimertinib monotherapy and combination therapy should be individualized based on patient factors including performance status, medical comorbidities, frailty, age, patient preferences for quality of life vs aggressive treatment, and genomic features such as comutations or resistance mechanisms, with shared decision-making playing a crucial role given the incurable nature of the disease.
