Hatim Husain, MD

Articles

Emerging Strategies for Overcoming On/Off-Target Resistance in ALK-Positive NSCLC

July 9th 2025

Panelists discuss how resistance mechanisms in ALK-positive disease are driving development of next-generation inhibitors like NVL-655 that spare TRK to reduce neurocognitive toxicity while targeting compound resistance mutations, though the success of lorlatinib makes frontline trials challenging due to extremely long progression-free survival requiring decade-long studies.

Decoding Efficacy and Safety Outcomes Among Second- and Third-Generation ALK Inhibitors

July 9th 2025

Panelists discuss how lorlatinib has become the new standard of care for ALK-positive patients based on CROWN trial data showing unprecedented 5-year progression-free survival (60% at 5 years, median not reached) and superior central nervous system control compared with earlier agents like alectinib, despite unique metabolic and neurocognitive toxicities requiring careful management.

New Frontiers in KRAS Inhibition for Patients With NSCLC

July 2nd 2025

Panelists discuss how next-generation KRAS G12C inhibitors like divarasib, lifirafenib, and RMC-6291 (a RAS-ON inhibitor) show promising enhanced potency with response rates in the 50% range and extended PFS, offering hope for more effective treatment options and potential sequencing strategies.

CNS Surveillance and Management of Brain Metastases in Patients With KRAS G12C NSCLC

July 2nd 2025

CNS Metastases Management in KRAS G12C Patients Central nervous system (CNS) metastases affect approximately 40% of patients with KRAS G12C positive non–small cell lung cancer, presenting significant management challenges. Unlike EGFR- and ALK-positive patients who benefit from highly CNS-penetrant targeted agents, KRAS G12C patients have limited systemic options with proven intracranial activity. Stereotactic radiosurgery often becomes the preferred approach for CNS lesions, particularly when systemic options are exhausted after platinum-based chemotherapy and immunotherapy. For asymptomatic, small CNS metastases (≤5 mm without edema), systemic therapy initiation with close monitoring represents a reasonable approach. Immunotherapy and chemoimmunotherapy combinations demonstrate modest CNS response rates, while KRAS G12C inhibitors show approximately 40% to 43% intracranial response rates in untreated brain metastases. However, these response rates remain below 50%, necessitating careful patient monitoring and readiness for local ablative therapy. Surveillance strategies for CNS metastases vary among practitioners, with baseline MRI universally recommended but routine follow-up imaging practices differing. Some oncologists perform periodic surveillance scans for high-risk patients, while others monitor symptomatically. The lack of robust CNS activity from systemic agents emphasizes the importance of early detection and prompt local therapy intervention when CNS progression occurs.

Targeting KRAS: Emerging Frontline Options for Patients With NSCLC

June 25th 2025

Panelists discuss how KRAS G12C inhibitors are moving into frontline combination therapy with immunotherapy, highlighting KRYSTAL-7 data showing impressive efficacy in PD-L1–high patients (~28 months progression-free survival) but more modest results in PD-L1–low patients, with ongoing studies exploring optimal combination strategies.

Managing KRAS Inhibitor Safety and Hepatotoxicity

June 25th 2025

Panelists discuss how KRAS G12C inhibitors differentiate in their toxicity profiles, with sotorasib carrying higher hepatotoxicity risk especially post–checkpoint inhibitor therapy, while adagrasib shows more gastrointestinal toxicities, and the importance of washout periods to mitigate liver toxicity.

Evaluating Efficacy Outcomes of TKI Therapies in KRAS G12C-Mutated NSCLC

June 18th 2025

Panelists discuss how 2 FDA-approved KRAS G12C inhibitors (adagrasib and sotorasib) perform in second-line therapy after immunotherapy and chemotherapy, with both showing improved progression-free survival versus docetaxel despite modest gains, leading to their adoption as standard of care due to better tolerability profiles.

KRAS G12C-Mutated NSCLC: Current Treatment Paradigms

June 18th 2025

Panelists discuss how critical broad-panel next-generation sequencing is for all patients with non–small cell lung cancer to enable biomarker-guided treatment, with focus on KRAS G12C mutations found in 12% to 14% of patients and consideration of PD-L1 expression levels and comutations when selecting frontline therapy.

Charting the Future: Key Therapies for Managing EGFR-Mutant NSCLC

December 3rd 2024

This episode focuses on exploring additional therapeutic options for managing previously treated advanced or metastatic EGFR-mutated NSCLC, highlighting strategies to optimize patient survival across various stages of disease progression.

Navigating Treatment Choices: Clinically Meaningful Outcomes to Look for in HERTHENA-Lung02

November 26th 2024

This episode discusses the desired outcomes from the HERTHENA-Lung02 trial that would justify using HER3-DXd before platinum and pemetrexed chemotherapy while also exploring the potential benefits of amivantamab, including its PFS advantage and the observed trend toward improved OS in this treatment setting.

HERTHENA-Lung02 Trial: Exploring the Role of Patritumab Deruxtecan in Advanced EGFR-Mutant NSCLC

November 26th 2024

This episode summarizes the HERTHENA-Lung02 trial and examines the average duration of response to platinum-based chemotherapy in patients with advanced EGFR-mutated NSCLC who have previously undergone multiple lines of EGFR TKI therapy, discusses strategies for community oncologists to tackle diverse resistance mechanisms to third-generation TKIs, and evaluates the importance of tolerability in sparing platinum-based chemotherapy compared with using ADCs in subsequent treatment lines.

Integrating HER3-DXd: Clinical Considerations for Future Approval and Implementation in Practice

November 19th 2024

This episode explores management strategies for hematologic toxicities arising within the first 3 weeks of treatment with HER3-DXd, discusses the potential integration of HER3-DXd into clinical practice upon approval, and identifies unmet needs and suitable patient populations for future clinical trials evaluating HER3-DXd based on insights from the HERTHENA-Lung01 trial results.

Evaluating Response Rates in HERTHENA-Lung01: Insights on HER3-DXd

November 19th 2024

This episode reviews the response rates reported in the HERTHENA-Lung01 trial among patients with advanced NSCLC exhibiting various resistance mechanisms, evaluates the clinical significance of responses to HER3-DXd based on HER3 expression scores, discusses the relevance of the reported overall DOR, median PFS, and OS, and examines the CNS ORR among patients with baseline brain metastases in relation to the ORRs.

Adverse Event Management and Resistance Mechanisms: Key Considerations for Datopotamab Deruxtecan in Advanced NSCLC

November 12th 2024

This episode addresses strategies for mitigating and managing adverse events associated with Dato-DXd in patients with advanced NSCLC, explores how the drug’s structure may help prevent acquired resistance mechanisms that are common with TKIs, and discusses the broader implications of integrating Dato-DXd and other ADCs into the treatment landscape for this patient population.

Impressions From TROPION-Lung05: Dato-DXd in Heavily Pretreated Advanced NSCLC

November 12th 2024

This episode discusses the impressive ORR of more than 40% from the phase 2 TROPION-Lung05 trial of Dato-DXd in patients with EGFR-mutated advanced NSCLC, its clinical impact on those treated with 3 or more prior therapies, and explores the potential of Dato-DXd as a practice-changing therapy, given the median DOR of 7 months and DCR of 79%.

Managing Toxicities With TROP2-Directed ADCs in Advanced NSCLC: Best Practices and Management Strategies

November 5th 2024

This episode examines the management of ILD/pneumonitis associated with TROP2-directed ADCs in patients with advanced NSCLC and strategies for mitigating these risks, addresses hematologic toxicities related to docetaxel, and discusses the improved tolerability and lower incidence of severe treatment-emergent adverse events with Dato-DXd compared with docetaxel.

Role of Datopotamab Deruxtecan in Advanced NSCLC: Insights From TROPION-Lung01

November 5th 2024

This episode covers current sequencing strategies for NSCLC after targeted therapies and platinum chemotherapy, discusses the COMPEL trial with osimertinib, reviews OS and PFS end points from the TROPION-Lung01 study, examines hypotheses behind differential PFS responses in nonsquamous vs squamous NSCLC, and addresses what constitutes a clinically meaningful, durable response in heavily pretreated patients with advanced NSCLC and actionable genomic alterations.

Targeted ADCs vs Chemotherapy in Heavily Pretreated NSCLC: Clinical Benefits and Challenges

October 29th 2024

This episode discusses the urgent need for more effective and tolerable therapies for patients with EGFR-mutated NSCLC who have exhausted targeted treatments, comparing the clinical benefits of a targeted ADC approach vs chemotherapy, with a focus on the TROPION-Lung01 study of Dato-DXd vs docetaxel for heavily pretreated advanced/metastatic NSCLC with actionable genomic alterations.

Tailoring Treatment by Stage: Insights From ADAURA for Stage IB to IIIA EGFR-Mutated NSCLC

October 29th 2024

This episode highlights the significance of third-generation EGFR TKIs in delaying subsequent therapies for resectable, stage IB to IIIA EGFR-mutated NSCLC, explores the risks of postresection treatments for disease progression, and discusses treatment considerations for patients across different stages, focusing on the ADAURA trial outcomes for stage IB to IIIA NSCLC.

Osimertinib in Resected Stage IB to IIIA NSCLC: Perspectives on Its Use for Less Common EGFR Mutations

October 22nd 2024

Although the NCCN guidelines recommend osimertinib as an adjuvant therapy option, what is your position on its use for completely resected stage IB to IIIA NSCLC with less common EGFR activating mutations, such as exon 20 insertion?

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