Joshua K. Sabari, MD

Panelists discuss the management of treatment-associated interstitial lung disease (ILD) and pneumonitis, emphasizing diagnostic strategies, therapeutic options, and patient monitoring.

Panelists discuss strategies for managing adverse events (AEs) related to antibody-drug conjugates (ADCs), focusing on prevention, early detection, and treatment of these effects.

Panelists discuss second-line treatment options and emerging approaches for HER2-mutated non–-small cell lung cancer (NSCLC), highlighting novel therapies and clinical strategies.

Panelists discuss the role of HER2 mutations in non–-small cell lung cancer (NSCLC), focusing on diagnostic approaches, clinical implications, and targeted treatment strategies.

Panelists discuss the presentation and management of a case involving HER2-mutated metastatic non–-small cell lung cancer (NSCLC), exploring treatment options and clinical decision-making

Panelists discuss the management of metastatic non–-small cell lung cancer (NSCLC) with a ROS1 alteration in patients with central nervous system (CNS) involvement, focusing on treatment strategies and challenges.

Panelists discuss the management of adverse events (AEs) associated with ROS1 inhibition, emphasizing strategies for prevention, monitoring, and treatment of adverse effects.

Panelists discuss treatment decision-making for metastatic non–-small cell lung cancer (NSCLC) with a ROS1 alteration, focusing on targeted therapies and personalized treatment strategies.

Panelists discuss next-generation ROS1 inhibition, highlighting emerging therapies, their mechanisms of action, and potential benefits for patients with ROS1-positive metastatic non–small cell lung cancer.

Panelists discuss the presentation and management of a case involving metastatic non–-small cell lung cancer (NSCLC) with a ROS1 alteration, focusing on treatment approaches and clinical considerations

Panelists discuss the emerging potential of KRAS inhibition in metastatic cancer treatment, exploring novel therapies and their promise for patients with KRAS-mutated tumors.

Panelists discuss individualized treatment selection for KRAS-mutated metastatic non–-small cell lung cancer (NSCLC), focusing on targeted therapies and personalized approaches to improve patient outcomes.

Panelists discuss the efficacy and safety of KRAS inhibitors for non–-small cell lung cancer (NSCLC), evaluating clinical trial results and their potential impact on treatment strategies.

Panelists discuss second-line treatment decision-making for KRAS-mutated metastatic non–-small cell lung cancer (NSCLC), focusing on available therapies and personalized approaches based on patient characteristics.

Panelists discuss first-line treatment decision-making for KRAS-mutated metastatic non–-small cell lung cancer (NSCLC), focusing on the selection of targeted therapies and factors influencing clinical choices.

Panelists discuss the use of RNA-based molecular panels in metastatic non–-small cell lung cancer (NSCLC), highlighting their role in guiding personalized treatment decisions and improving patient outcomes.

Panelists discuss decision-making in metastatic non–-small cell lung cancer (NSCLC) when molecular testing results are delayed, focusing on strategies to optimize treatment while awaiting results.

Panelists discuss the role of molecular testing in metastatic non–-small cell lung cancer (NSCLC), emphasizing its importance in identifying actionable mutations and guiding personalized treatment strategies.

Joshua K. Sabari, MD, evaluates the objective clinical outcomes of emerging targeted therapies for ES-SCLC, comparing them with second-line topotecan and CAV regimens, while discussing the potential of various compounds for platinum-sensitive vs platinum-resistant subgroups. He also considers the applicability of TIGIT immunotherapy, highlighting the need for robust clinical trial data on its safety and efficacy as both monotherapy and in combination, and he reflects on whether tiragolumab is more suited for chemotherapy-naive non–small cell lung cancer than for ES-SCLC, based on the phase 2 CITYSCAPE trial results.

Joshua K. Sabari, MD, discusses the antitumor activity of second-line lurbinectedin, noting an ORR of 45%, a median DOR of 6.2 months, and a median OS of 11.2 months in patients with relapsed SCLC, and emphasizes the need for further studies to validate these findings in those with longer chemotherapy-free intervals while considering factors that may lead to lurbinectedin’s use over chemotherapy in candidates for platinum rechallenge, as well as the potential role of G-CSFs for prophylaxis.

Joshua K. Sabari, MD, describes the mechanism of action of lurbinectedin as a synthetic alkaloid that binds to guanine residues in the minor groove of DNA, forming adducts that disrupt DNA repair mechanisms and promote apoptosis in cancer cells, noting that its action contrasts with traditional alkylating agents by specifically interfering with DNA-protein interactions and transcription processes.

Joshua K. Sabari, MD, evaluates the potential of ifinatamab deruxtecan in combination with atezolizumab, with or without platinum-based chemotherapy, as first-line induction or maintenance therapy in ES-SCLC, emphasizing that statistically significant end points such as improved PFS and OS would be essential for clinical application in this patient population.

Joshua K. Sabari, MD, discusses the potential treatment synergies expected from combining MK-6070, a trispecific T-cell engager, with ifinatamab deruxtecan, noting that specific patient and disease factors (eg, tumor expression profiles and previous treatment responses) could influence the decision to pursue dual T-cell engager therapy in early clinical development.

Joshua K. Sabari, MD, discusses how the dosing schedule of ifinatamab deruxtecan offers advantages in terms of simplicity and treatment adherence vs topotecan and lurbinectedin, suggesting that it may enhance the overall quality of life for patients undergoing treatment for SCLC.

Joshua K. Sabari, MD, discusses the efficacy outcomes from the Ideate-Lung02 trial, noting the 52.4% ORR, 5.9-month median DOR, and 12.2-month OS and emphasizing that a 12-month OS is clinically meaningful for this patient population following a median of 2 prior lines of therapy.

Joshua K. Sabari, MD, discusses whether individual B7-H3 analysis is available at his institution, noting that, if it is, he obtains IHC for both PD-L1 and B7-H3 expression levels in all patients with SCLC. If B7-H3 testing becomes available, he would consider adding it to the biomarker assay, particularly at the time of diagnosis or recurrence.

Joshua K. Sabari, MD, discusses the unique mechanism of action of B7-H3, highlighting its role as an immune checkpoint regulator that is overexpressed in SCLC and associated with poor prognosis. He notes that B7-H3 blockade can enhance CD8-positive T-cell activity and may serve as a promising treatment option for SCLC that has progressed after platinum-based chemotherapy.

Joshua K. Sabari, MD, discusses the anticipated clinical benefits of adding tarlatamab to durvalumab as maintenance therapy for patients with ES-SCLC, highlighting that statistically significant trial end points, such as improved PFS and OS, could encourage community oncologists to adopt this dual maintenance approach.

Joshua K. Sabari, MD, discusses the future treatment potential of tarlatamab as a combination therapy with other anticancer agents for previously treated SCLC, suggesting that it could enhance efficacy and improve patient outcomes following 2 or more lines of prior therapy.

Joshua K. Sabari, MD, discusses the expected PFS of 3 to 6 months and OS of 6 to 12 months for second- or third-line therapy in previously treated patients with relapsed/refractory SCLC.