Joshua K. Sabari, MD

Clinical Pearls for the Testing and Treatment of HER2-Mutation mNSCLC in the Community Setting

October 15th 2025

Panelists discuss clinical pearls for community oncologists, emphasizing that comprehensive testing is essential since zongertinib offers dramatic improvements with 75% response rates and progression-free survival exceeding 12 months in HER2 exon 20 mutations, while noting that HER2 immunohistochemistry testing shouldn’t be neglected for identifying patients who may benefit from trastuzumab deruxtecan, requiring a multilayered molecular profiling approach encompassing DNA, RNA, and protein analysis to provide new hope for patients with HER2-mutant disease.

Looking Forward: Combination Therapy for HER2 Mutation mNSCLC

October 15th 2025

Panelists discuss how combination therapies represent the future of HER2 mutation treatment, drawing parallels to successful EGFR combination strategies, with particular interest in anti-VEGF agents and potentially anti-PD-1/PD-L1 therapies, while noting that zongertinib’s favorable tolerability profile makes it an ideal candidate for combination approaches compared with more toxic agents like trastuzumab deruxtecan or sevabertinib, though current trial designs should incorporate 3-armed studies to evaluate up-front combination strategies rather than sequential monotherapy comparisons.

Incorporating Shared Decision-Making and Patient Preference in Treatment Choice for HER2-Mutation mNSCLC

October 8th 2025

Panelists discuss how shared decision-making between zongertinib and trastuzumab deruxtecan (T-DXd) in second-line treatment involves presenting key differences to patients, including that T-DXd requires intravenous (IV) infusion with chemotherapy-like toxicities and closer monitoring (including cardiac function), while zongertinib is an oral, once-daily targeted therapy with better patient-reported outcomes and functional status improvements, fewer clinic visits after initial monitoring, and superior tolerability, leading to a preference for zongertinib first followed by T-DXd sequencing.

Sequencing Treatment Options in HER2-Mutation mNSCLC

October 8th 2025

Panelists discuss how treatment sequencing for HER2-mutation non–small cell lung cancer (NSCLC) prioritizes zongertinib over trastuzumab deruxtecan in the second-line setting due to superior efficacy and tolerability, while noting that special populations like patients with baseline lung dysfunction (favoring zongertinib to avoid interstitial lung disease risk) or CNS (central nervous system) metastases (where zongertinib shows promising brain activity but may require concurrent radiation for larger lesions) require individualized, case-by-case management with close monitoring and early imaging follow-up.

Dr Sabari on the FDA Approval of Maintenance Lurbinectedin Plus Atezolizumab for ES-SCLC

October 2nd 2025

Joshua K. Sabari, MD, discusses the significance of the FDA approval of first-line maintenance therapy with lurbinectedin plus atezolizumab for ES-SCLC.

Patient Clinical Scenario: 2L Treatment of mNSCLC With HER2 Mutations

October 1st 2025

Panelists discuss a clinical scenario involving a 73-year-old Asian woman with stage 4 lung adenocarcinoma harboring a HER2 exon 20 insertion mutation (A775-G776 YVMA) who initially responded to carboplatin, pemetrexed, and pembrolizumab for 4 cycles followed by maintenance therapy, but now presents with progressive cough and shortness of breath suggesting clinical progression, requiring decisions about next-step management in this fit patient with good performance status.

Emerging Treatment Options in 2L Treatment of mNSCLC With HER2 Mutations

October 1st 2025

Panelists discuss how emerging second-line treatment options for HER2-mutant non–small cell lung cancer (NSCLC) include sevabertinib (a dual HER2/EGFR exon 20 inhibitor with higher gastrointestinal toxicity but similar efficacy to zongertinib) and other brain-penetrant tyrosine-kinase inhibitors (TKIs) in development, while noting that multiple ongoing phase 3 trials are studying frontline comparisons of these targeted therapies vs chemotherapy plus immunotherapy, creating a complex treatment landscape where the principle of using the best therapy first must consider efficacy, tolerability, and quality-of-life factors.

Beamion LUNG-1: Examining the Efficacy and Safety of Zongertinib in 2L Treatment of mNSCLC With HER2 Mutations

September 24th 2025

Panelists discuss how the Beamion LUNG-1 trial demonstrated zongertinib’s impressive efficacy in second-line treatment of HER2–mutant non–small cell lung cancer (NSCLC)with a 75% response rate and 14.1-month duration of response in previously treated patients, while showing a favorable safety profile as a true targeted therapy with mainly low-grade diarrhea and minimal toxicities compared with chemotherapy-like side effects, and maintaining activity even after prior trastuzumab deruxtecan treatment with a 50% response rate.

Second-Line Treatment Options for mNSCLC With HER2 Mutations

September 24th 2025

Panelists discuss how second-line treatment options for HER2-mutant non–small cell lung cancer (NSCLC), particularly trastuzumab deruxtecan (T-DXd), require careful management of significant adverse effects, including interstitial lung disease/pneumonitis (especially concerning after prior immunotherapy due to the antibody’s immune-active properties), topoisomerase inhibitor–related gastrointestinal toxicity requiring strong antiemetic protocols, and cytopenias leading to fatigue and infection risk, making it more complex to manage than traditional precision medicine targeted therapies.

Frontline Treatment Options for mNSCLC With HER2 Mutations

September 17th 2025

Panelists discuss how frontline treatment for HER2 mutant non–small cell lung cancer (mNSCLC) lacks FDA-approved targeted therapies, with current approaches varying between platinum-based chemotherapy with or without immunotherapy (such as the KEYNOTE-189 regimen), though some clinicians avoid immunotherapy in this population due to limited proven benefit in never-smokers who make up 60% of HER2-mutation patients, while considering whether to extrapolate from recently approved second-line targeted therapies like zongertinib.

Opportunities for HER2 Molecular Testing Education in mNSCLC

September 17th 2025

Panelists discuss how community oncologists can best serve patients by understanding that lung cancer is no longer 1 disease requiring uniform treatment, emphasizing that comprehensive molecular testing including both next-generation sequencing and immunohistochemistry (IHC) is critical for identifying targetable alterations like HER2 mutations that now have FDA-approved targeted therapies, making broad panel testing essential for optimal patient outcomes in 2025.

The Clinical Utility of ctDNA Testing in HER2- Mutation mNSCLC

September 10th 2025

Panelists discuss how circulating tumor DNA (ctDNA) testing is valuable for up-front molecular profiling in all locally advanced or metastatic lung cancer patients to accelerate treatment decisions, but longitudinal ctDNA monitoring is not yet standard practice for assessing treatment response in HER2 mutations, though it can be useful at disease progression to identify resistance mechanisms and guide subsequent therapy decisions.

Distinguishing HER2 Alterations in mNSCLC

September 10th 2025

Panelists discuss how HER2 alterations in lung cancer differ from other cancers like breast cancer, where overexpression is more common and targetable with antibody-drug conjugates (ADCs), while in lung cancer the focus is primarily on HER2 exon 20 insertion mutations and other tyrosine kinase domain mutations, requiring both next-generation sequencing (NGS) and immunohistochemistry (IHC) testing since liquid biopsies can detect mutations but not overexpression.

Reviewing Key Data in Resectable and ROS1+ NSCLC With Drs Florez and Sabari

September 9th 2025

Narjust Florez, MD, and Joshua K. Sabari, MD, sit down with Chandler Park, MD, FACP, to discuss the latest abstracts in lung cancer presented during the International Association for the Study of Lung Cancer 2025 World Conference on Lung Cancer.

HER2 Alteration Prevalence and Testing Best Practices in mNSCLC

September 3rd 2025

The Clinical Importance of HER2 Testing in mNSCLC

September 3rd 2025

Telisotuzumab Vedotin Represents a New Treatment Development for c-Met–Overexpressing NSCLC: With Joshua K. Sabari, MD

July 24th 2025

Dr Sabari highlights key research investigating telisotuzumab vedotin in patients with c-Met–overexpressing non–small cell lung cancer.

Looking Ahead in NSCLC Oncodrivers and Targeted Therapies

July 23rd 2025

Panelists discuss how ASCO 2025 highlighted exciting advances in targeted therapy including neoadjuvant approaches, dynamic biomarkers like circulating tumor DNA, mixed results with HER3-directed antibody-drug conjugates (ADCs) in the EGFR space, but promising data with trastuzumab-based ADCs, emphasizing the critical importance of comprehensive biomarker testing to ensure no patients miss potentially life-changing targeted therapies.

Dr Sabari on Efficacy of Zidesamtinib in TKI-Pretreated, Advanced, ROS1+ NSCLC

July 18th 2025

Joshua K. Sabari, MD, discusses response rates observed with zidesamtinib in patients with advanced ROS1-positive non–small cell lung cancer.

Real-World (RW) Outcomes and Novel Strategies in ROS1-Positive NSCLC

July 16th 2025

Panelists discuss how real-world data becomes crucial for guiding treatment decisions in rare subsets like ROS1-positive patients where head-to-head trials are challenging, and how next-generation inhibitors like NVL-520 and taletrectinib aim to improve efficacy while reducing TRK-related toxicities through more selective targeting.