Case Based Peer Perspectives

Dr. Evan Wu (The Oncology Institute of Hope and Innovation) leads a case-based discussion on first-line management of HER2-mutant non-small cell lung cancer (NSCLC) in William, a 76-year-old Black man with a HER2 A775_G776insYVMA mutation, mild hepatic impairment from chronic hepatitis B, seven daily medications, and significant transportation barriers. Dr. Wu walks through biomarker testing when tissue is insufficient, interpretation of PD-L1 status with a co-occurring driver mutation, selection among four FDA-approved HER2-directed therapies, drug–drug interaction and liver monitoring strategies, second-line sequencing after progression on zongertinib, clinical trial representation concerns in Black patients, and real-world barriers around cost and adherence. Designed for community oncologists, academic oncologists, and advanced practice providers navigating the rapidly changing HER2-mutant NSCLC treatment landscape.

Dr. Matthew Gumbleton (Huntsman Cancer Institute at the University of Utah) leads a case-based discussion on first-line treatment selection in EGFR-mutated metastatic non-small cell lung cancer (NSCLC) with a TP53 co-mutation. The patient, Mrs. Chen, is a 58-year-old never-smoker, working full time and living 75 minutes from clinic, who wants to maximize long-term survival and minimize treatment burden. Dr. Gumbleton reviews the three preferred first-line options—osimertinib, amivantamab plus lazertinib, and osimertinib plus chemotherapy—against the high-risk biology of TP53 co-mutation, compares MARIPOSA and FLAURA2 efficacy and CNS data, and discusses safety profiles, treatment burden with subcutaneous amivantamab, and preservation of later-line options.

Dr. Deborah Doroshow (Icahn School of Medicine at Mount Sinai) presents a case-based discussion on second-line treatment selection in HER2-mutant non-small cell lung cancer (NSCLC) after progression on chemo-immunotherapy. The session centers on Sandra, a 54-year-old never-smoker with stage IVA adenocarcinoma who developed brain metastases and was found to have a HER2 Y772_A775dup mutation at progression, 12 months after starting treatment with an incomplete upfront biomarker panel. Dr. Doroshow addresses incomplete molecular testing consequences, brain metastases management with stereotactic radiosurgery, comparative safety profiles of zongertinib, sevabertinib, and trastuzumab deruxtecan, financial toxicity navigation through patient assistance programs, and treatment sequencing strategies. The discussion emphasizes individualized decision-making based on patient factors, including interstitial lung disease risk, oral versus intravenous preferences, cost considerations, and adherence monitoring. Designed for community oncologists, academic physicians, and advanced practice providers seeking practical guidance in the rapidly evolving HER2-mutant NSCLC treatment landscape.

Dr. Luciano Costa from the University of Alabama at Birmingham presented a comprehensive case-based discussion on bispecific therapy for relapsed/refractory multiple myeloma. The program centered on a 72-year-old male with triple-class refractory disease after four prior therapy lines who remains BCMA-naive and prefers community-based treatment while declining CAR-T cell therapy.

Key topics included strategic BCMA-directed therapy sequencing, emphasizing that sequential BCMA targeting creates cross-resistance patterns requiring optimal initial selection. Dr. Costa analyzed efficacy patterns showing bispecific T-cell engagers operate in "all-or-nothing" patterns with 60-75% response rates and durable responses among responders. Critical safety management focused on infection risk mitigation through universal IVIG replacement, antibiotic prophylaxis, and distinguishing cytokine release syndrome from infection.

The transformative MajesTEC-3 trial results demonstrated teclistamab-daratumumab combination superiority with 83% three-year progression-free survival and hazard ratio 0.17. Dr. Costa advocated for community-based bispecific delivery, challenging perceptions about treatment complexity while emphasizing these agents represent foundational multiple myeloma therapy destined to fundamentally alter treatment paradigms across all disease stages.

Dr. Ajay Nooka presented a comprehensive case-based perspective on managing patients with early relapsed multiple myeloma, focusing on treatment selection after lenalidomide maintenance failure. The program covered essential topics including disease progression definitions, treatment evolution from doublets to current quadruplet regimens, and the critical importance of achieving minimal residual disease negativity, particularly for high-risk patients.

Central to the discussion was the paradigm-shifting MajesTEC-3 trial, demonstrating unprecedented efficacy of teclistamab plus daratumumab with an 83% reduction in progression/death risk and 83% of patients progression-free at 3 years. Dr. Nooka outlined a systematic treatment algorithm stratifying 100 patients: 50% requiring immediate treatment (high-risk cytogenetics, functional high-risk, or symptomatic progression) and 50% allowing careful observation.

Key management topics included distinguishing CD38 antibody exposure from refractoriness, bispecific antibody safety protocols, and the importance of academic-community collaboration for optimal treatment sequencing. The program concluded with future directions showing bispecific antibodies moving toward frontline settings, with preliminary data demonstrating near-universal MRD negativity in combination therapies, representing a transformative advancement in multiple myeloma treatment.

This Case Based Peer Perspectives program features Dr Shaheen discussing the management of a 54 year old woman with a progressive, well differentiated pancreatic neuroendocrine tumor after prior treatment with somatostatin analog therapy and peptide receptor radionuclide therapy. Using a real world case, the discussion reviews prognosis assessment, treatment sequencing, guideline informed decision making, and incorporation of emerging clinical data.

The program also emphasizes shared decision making, quality of life considerations, and long term treatment planning to support individualized care in advanced pancreatic neuroendocrine tumors.

In this Case Based Peer Perspectives discussion, Christopher Lieu, MD, medical oncologist at the University of Colorado, reviews the management of a patient with progressive small bowel neuroendocrine tumor and liver metastases following somatostatin analog therapy. Drawing on clinical trial evidence and real world experience, Dr Lieu discusses prognosis, treatment sequencing, and the practical application of therapies including peptide receptor radionuclide therapy and targeted agents. This program provides clear, practice focused insights to support community oncologists in navigating therapeutic decision making for patients with advanced small bowel neuroendocrine tumor.

This Case-Based Peer Perspectives program explores contemporary diagnosis, assessment, and treatment sequencing strategies for chronic graft-versus-host disease (cGVHD) following allogeneic stem cell transplantation. Dr. Leyla Shune emphasizes the use of NIH consensus criteria to systematically evaluate organ involvement as well as the continued importance of clinical judgment in the absence of validated biomarkers. Through analysis of a detailed patient case, she illustrates challenges such as steroid dependence, disease progression, and multi-organ involvement, highlighting how objective measures guide therapy escalation. The discussion reviews FDA-approved systemic options across second- and third-line settings, focusing on mechanism-driven selection among JAK, ROCK, BTK, and CSF1 receptor–targeted therapies. Particular attention is given to sclerotic and pulmonary cGVHD, where early intervention may prevent irreversible fibrosis. Real-world experience, safety considerations, patient preference, and combination strategies are integrated throughout. Dr. Shune also presents a forward-looking perspective on clinical trials, earlier-line use of targeted agents, and future innovations to reduce treatment burden and improve long-term outcomes.

This Targeted Oncology Case-Based Peer Perspective program, led by Dr. Zachariah DeFilipp of Massachusetts General Hospital, focuses on optimizing treatment sequencing in chronic graft-versus-host disease (cGVHD) following allogeneic stem cell transplantation. The discussion emphasizes practical, real-world decision-making across lines of therapy, integrating NIH diagnostic criteria, patient-reported symptoms, and evolving clinical trial data. Dr. DeFilipp reviews the limitations of corticosteroids as first-line therapy, the central role of ruxolitinib in steroid-refractory disease, and emerging targeted agents such as belumosudil and axatilimab in later lines. Through a longitudinal patient case, the program highlights challenges with durability of response, fibrotic and pulmonary involvement, and timing of therapy escalation. He also explores discrepancies between clinical trial outcomes and real-world experience, logistical considerations influencing oral versus IV therapy selection, and the growing interest in combination strategies and earlier use of targeted agents to alter the long-term trajectory of cGVHD.

Presentation focusing on advances in the first-line treatment of EGFR-mutated advanced or metastatic non-small-cell lung cancer.

Presentation focusing on advances in the first-line treatment of EGFR-mutated advanced or metastatic non-small-cell lung cancer.

A panelist discuss how emerging treatments such as tarlatamab and lurbinectedin are reshaping the management of relapsed extensive-stage small cell lung cancer, emphasizing efficacy, safety, and accessibility. They highlight that future advances depend on addressing real-world barriers while integrating novel agents such as bispecifics and antibody-drug conjugates into clinical practice.

An expert discusses how adding lurbinectedin to maintenance atezolizumab therapy after standard induction treatment significantly improves progression-free survival and overall survival in patients with extensive-stage small cell lung cancer, with manageable toxicity profiles and the rationale for moving treatment earlier to prevent disease progression in a patient population where many never receive subsequent therapies.

Raji Shameem, MD, discusses how to approach treatment decisions for patients with metastatic pancreatic adenocarcinoma, covering first-line therapy options including NALIRIFOX and modified FOLFIRINOX based on performance status, the importance of genetic testing, clinical trial evidence supporting 3-drug vs 2-drug regimens, and proactive adverse event management strategies.

Farshid Dayyani, MD discusses how the NALIRIFOX regimen (nanoliposomal irinotecan, oxaliplatin, leucovorin, and 5-FU) has emerged as a promising frontline treatment option for locally advanced pancreatic adenocarcinoma based on the NAPOLI-3 trial results, with manageable toxicities including diarrhea and cytopenia that can be effectively addressed through dose modifications and supportive care.

An expert discusses how CAR T-cell therapy and bispecific antibodies are transforming relapsed/refractory large B-cell lymphoma treatment by providing durable remissions and personalized care options, while emphasizing the importance of timely referral, multidisciplinary coordination, patient access, and ongoing management to optimize outcomes.

An expert explains that for this 60-year-old man with primary refractory DLBCL, early referral to CAR T-cell therapy is critical—supported by trials like ZUMA-7 showing superior survival and faster recovery compared to traditional treatments—while overcoming eligibility misjudgments, logistical barriers, and balancing safety profiles of different CAR T products through coordinated, patient-centered care optimizes outcomes in this high-risk population.

Raji Shameem, MD discusses how luspatercept has become his preferred frontline treatment for lower-risk MDS patients with anemia due to its superior efficacy compared to ESAs in the COMMANDS trial, showing 60% of patients achieving transfusion independence versus 30% with ESAs, along with impressive durability of response and a promising trend toward improved overall survival.

A panelist discusses how luspatercept has become a convenient and effective treatment for anemia in lower-risk MDS, providing durable transfusion independence and quality-of-life improvements across diverse patients, while emphasizing the importance of personalized therapy, regular dose adjustments, and ongoing development of novel agents to improve long-term outcomes.

An expert discusses first-line treatment options for EGFR-mutated advanced/metastatic non-small-cell lung cancer in a 55-year-old man.

An expert discusses how the case of a 74-year-old woman with newly diagnosed BPDCN underscores the importance of early recognition of skin and blood abnormalities, prompt diagnostic workup, and initiation of tagraxofusp with close monitoring to manage this aggressive hematologic malignancy effectively.

Nelson Chao, MD, MBA,discusses how effective management of GVHD requires comprehensive assessment of symptoms across multiple organ systems, strategic use of steroid therapy as first-line treatment with appropriate supportive care measures, timely recognition of steroid-refractory disease warranting JAK inhibition with ruxolitinib or other emerging therapies as supported by clinical trials like REACH3, vigilant monitoring of treatment-related adverse events through structured protocols, thorough patient education regarding treatment expectations, and a multidisciplinary approach to optimize both disease control and quality of life in transplant survivors.

Nagashree Seetharamu, MD, MBBS, discusses how immunotherapy integration with chemotherapy is transforming nasopharyngeal carcinoma treatment, citing JUPITER-02 and DIPPER study data showing benefits even with low EBV levels, while emphasizing the importance of patient selection factors, multidisciplinary care, and vigilant monitoring for immune-related adverse events in community practice.

An expert discusses the clinical challenges and management strategies for a 48-year-old man with recurrent nasopharyngeal carcinoma and a 53-year-old woman with metastatic nasopharyngeal carcinoma.

An expert discusses the emerging treatment landscape in myeloproliferative neoplasms (MPNs), focusing on the transition from current practices to emerging therapies.

Marlise Rachael Luskin, MD, MSCE, discusses the case of a man aged 62 years who is newly diagnosed with blastic plasmacytoid dendritic cell neoplasm (BPDCN). She provides an overview of the patient’s case and recommended treatment approaches. She discusses the role of CD123 targeted therapy (tagraxofusp) and the evolving landscape of BPDCN treatment options.

Pedro Barata, MD, MSc, FACP, discussessequencing for a relapsed/refractory metastatic renal cell carcinoma patient case. He also discusses how third-line mRCC therapy aims for disease control and symptom palliation with careful toxicity management. Options include cabozantinib, lenvatinib/everolimus, and tivozanib, with selection based on prior therapy, comorbidities, and tolerability.

Amit Mahipal, MD, discusses the patient case of a 57-year-old woman diagnosed with advanced unresectable hepatocellular carcinoma (uHCC). He also discusses how first-line systemic therapy for advanced uHCC focuses on tyrosine kinase inhibitors (lenvatinib, sorafenib), considering patient factors, monitoring response depth, managing adverse events, and balancing efficacy with quality of life.