What I Tell My Patients About ...

The Importance of Biomarker Testing for Patients with Non-Small Cell Lung Cancer (NSCLC)

• Spectrum, prevalence and current clinical relevance of genomic alterations in patients with NSCLC
• Available platforms for genomic evaluation; advantages and limitations of next-generation sequencing versus one-off testing
• Accuracy of various testing methods in identifying different genomic abnormalities, such as gene fusions
• Clinical utility of plasma-based assays to document the presence of genomic alterations
• Role of repeat biomarker testing in the care of patients with progressive NSCLC

Targeted Therapy for NSCLC with EGFR Mutations

• Published findings with adjuvant osimertinib after complete tumor resection for Stage IB to IIIA NSCLC with an EGFR mutation
• Optimal first-line treatment for patients with metastatic NSCLC with EGFR tumor mutations, including those with CNS metastases
• Spectrum and clinical relevance of resistance mechanisms in patients experiencing disease progression on osimertinib
• Antitumor activity of amivantamab/lazertinib in patients with progressive NSCLC with EGFR mutations
• Mechanistic similarities and differences among amivantamab, mobocertinib and other EGFR tyrosine kinase inhibitors
• Key data sets informing the use of mobocertinib and amivantamab for patients with EGFR exon 20 insertion mutations who have experienced disease progression on first-line chemotherapy

Tolerability and Other Practical Considerations with EGFR-Targeted Therapy for NSCLC

• Incidence of gastrointestinal and dermatologic adverse events (AEs) with osimertinib; strategies for prevention and amelioration
• Comparative tolerability of osimertinib in the adjuvant and metastatic settings; appropriate threshold for dose reduction, delay or discontinuation for patients with NSCLC receiving adjuvant osimertinib
• Spectrum of common toxicities associated with amivantamab and mobocertinib in patients with EGFR exon 20 insertion mutations
• Appropriate monitoring for and management of less-common side effects of amivantamab, such as interstitial lung disease (ILD)/pneumonitis and ocular toxicities, and of mobocertinib, such as QTc prolongation or torsade de pointes, cardiac toxicity and ILD/pneumonitis

ALK Inhibitors in the Treatment of NSCLC

• Key findings with novel ALK inhibitors, such as alectinib, brigatinib or lorlatinib, as first-line therapy for patients with ALK-rearranged NSCLC
• Clinical factors in the choice of up-front treatment for patients with metastatic NSCLC and ALK rearrangements
• Differential CNS permeability of approved ALK inhibitors; implications for the management of ALK-positive brain metastases
• Selection of treatment for patients with disease progression on first-line ALK inhibition; utility of multiple lines of ALK-targeted therapy

The Tolerability of ALK Inhibitors

• Spectrum, frequency and severity of AEs associated with ALK-targeted agents, such as gastrointestinal disorders, CNS effects, hepatotoxicity, musculoskeletal pain, pneumonitis, cardiac toxicities, hyperglycemia, visual disturbances and peripheral neuropathy
• Optimal monitoring for and management of ALK inhibitor-related toxicities
• Initial dosing and appropriate dose-modification strategies with approved ALK inhibitors
• Role of switching to an alternative ALK inhibitor for patients who are experiencing unacceptable toxicity

Treatment Options for KRAS G12C-Mutated NSCLC

• Explanation for the historical perception of KRAS as an “undruggable” target
• Mechanistic similarities and differences between the novel KRAS G12C inhibitors sotorasib and adagrasib
• Principal efficacy findings with sotorasib and with adagrasib for pretreated KRAS G12C-mutated NSCLC
• Optimal integration of sotorasib and adagrasib into practice; factors guiding selection between these agents

The Tolerability of KRAS G12C Inhibitors

• Spectrum and management of commonly occurring toxicities with sotorasib, such as gastrointestinal disorders, musculoskeletal pain and fatigue
• Strategies to monitor for and manage potentially serious AEs with sotorasib, such as hepatotoxicity and ILD/pneumonitis
• Tolerability profile of adagrasib; similarities and differences in comparison to sotorasib
• Rates of QT prolongation and other cardiac issues observed with adagrasib; appropriate monitoring and management

The Role of RET Inhibitors in the Management of Advanced NSCLC

• Mechanisms of action of selpercatinib and pralsetinib; pharmacologic similarities and differences
• Clinical activity observed with selpercatinib and with pralsetinib in patients with RET fusion-driven advanced NSCLC, including those with previously untreated disease
• Optimal integration of selpercatinib and pralsetinib into therapy for patients with metastatic NSCLC and RET fusions; selecting between these agents
• Ongoing efforts to further define the role of RET inhibitors in the treatment of RET-driven NSCLC

The Tolerability of RET-Targeted Therapy

• Comparative tolerability profiles of selpercatinib and pralsetinib for NSCLC
• Recommended hepatic, blood pressure and cardiac monitoring for patients starting treatment with selpercatinib or pralsetinib
• Optimal management of treatment-emergent AEs reported with selpercatinib and with pralsetinib, such as hypertension, musculoskeletal pain, diarrhea, hepatotoxicity, ILD/pneumonitis, hemorrhage and QTc prolongation
• Other practical considerations with the use of RET inhibitors for NSCLC, such as drug-drug interactions and the need to withhold therapy before and after surgery

Other Targeted Therapies for Advanced NSCLC

• Efficacy of entrectinib and appropriate integration into therapy for patients with metastatic NSCLC with ROS1 mutations
• Published research supporting the recent FDA approval of trastuzumab deruxtecan (T-DXd) for HER2-mutated NSCLC
• Strategies to monitor for and manage common side effects of T-DXd, including ILD/pneumonitis
• Major efficacy findings with capmatinib and with tepotinib for patients with NSCLC with MET exon 14 mutations; integration into clinical practice and individualized selection between these agents

The Role of Immune Checkpoint Inhibitors in the Treatment of Localized and Locally Advanced NSCLC without Targetable Mutations

• Available and emerging data with neoadjuvant immunotherapy-based approaches for patients with resectable NSCLC
• Published data with atezolizumab and with pembrolizumab as adjuvant treatment
• Long-term findings with consolidation durvalumab after chemoradiation therapy for unresectable Stage III NSCLC; patient selection for and practical implementation of this approach
• Effect of chemoradiation therapy-associated esophagitis and/or pneumonitis on the decision to introduce durvalumab consolidation therapy

The Role of Anti-PD-1/PD-L1 Antibodies in Therapy for Metastatic NSCLC without Targetable Mutations

• Impact of PD-L1 expression on eligibility for front-line anti-PD-1/PD-L1-containing regimens; selection of an appropriate testing platform
• Recent therapeutic advances related to the use of anti-PD-1/PD-L1 antibodies as monotherapy or in combination with chemotherapy, chemobiologic therapy or anti-CTLA-4 antibodies for metastatic NSCLC
• Pathophysiology, incidence and management of immune-mediated and other AEs observed with anti-PD-1/PD-L1 antibodies

The Potential Utility of Tumor Treating Fields and Other Promising Investigational Strategies in NSCLC Management

• Mechanism of action of tumor treating fields and biologic rationale for their investigation in NSCLC; preclinical and early clinical activity observed in patients with advanced NSCLC
• Emerging positive findings with tumor treating fields in combination with immune checkpoint inhibition or docetaxel after failure of platinum-based therapy; potential ramifications for practice
• Rates and severity of skin toxicities associated with tumor treating fields and other practical considerations with this treatment modality
• Available efficacy and safety findings with and ongoing clinical research evaluating the TROP2-targeted agent datopotamab deruxtecan for metastatic NSCLC
• Ongoing studies evaluating tumor treating fields and other promising novel agents and strategies for metastatic NSCLC