Advances in Targeted Therapies for Non-Small Cell Lung Cancer

Zosia Piotrowska, MD, and Michelle Shiller, DO, AP/CP, MGP, explain the frequency of the different biomarkers in NSCLC, and steps clinicians might take to ensure timely and effective molecular testing for their patients.

Lauren Welch, MSN, NP-C, AOCNP, describes how she approaches management of patients with NSCLC and known high PD-L1 expression while she waits for pending biomarker testing results.

Drs Shiller and Piotrowska discuss use of broad genomic profiling according to the patient’s histologic subtype of NSCLC.

Nurse Practitioner Lauren Welch and Dr Michelle Shiller share whether next-generation sequencing is reflexively ordered at their institutions, turnaround times for this type of testing, and which panels they typically choose.

Zosia Piotrowska, MD, explains molecular testing methods that can discover molecular alterations in common biomarkers in patients with mNSCLC.

Joel Neal, MD, PhD, presents the case of a 66-year-old woman with no smoking history and a diagnosis of EGFR exon 20 mutation-positive mNSCLC.

Michelle Shiller, DO, AP/CP, MGP, describes the process of tissue biopsy testing at her institution from start to finish, and Zosia Piotrowska, MD, explains the likelihood of targetable alterations in cases of mNSCLC in patients with no smoking history.

The panel reviews the first- and second-line treatment options for the patient in the presented case, before and after knowing her molecular testing results.

A key opinion leader muses on the treatments she would consider for a patient with mNSCLC, an EGFR exon 20 mutation, and brain metastases.

Nurse Practitioner Lauren Welch and Dr Michelle Shiller explain if and when they would offer repeat liquid or tissue biopsies to a patient with mNSCLC, and discuss how often patients request “serial biopsies” for detecting treatment response and/or disease progression.

Dr Piotrowska highlights the currently approved targeted therapies for EGFR exon 20 mutation-positive mNSCLC.

Dr Joel Neal reviews data from the pivotal clinical trial leading to the FDA approval of mobocertinib for EGFR exon 20-mutated advanced or metastatic lung cancers.

Dr Neal discusses the design and outcomes of the CHRYSALIS study, investigating amivantamab for the treatment of EGFR exon 20-mutant advanced or metastatic lung cancer, and then briefly comments on a matched analysis of efficacy data on mobocertinib and amivantamab.

Dr Shiller emphasizes the heterogeneity between the various EGFR exon 20 mutations seen in patients with NSCLC, and describes strategies for effectively communicating actionable information about a patient’s mutation status to the clinicians receiving the reports.

Dr Piotrowska and Lauren Welch offer insight into results interpretation and subsequent treatment decision-making for patients with mNSCLC who are found to harbor an EGFR exon 20 insertion mutation through biomarker testing.

Dr Neal outlines second-line targeted treatment selection for the patient case, while Lauren Welch, MSN, NP-C, AOCNP, shares her experience with managing the adverse effects of mobocertinib in patients with EGFR exon 20-mutated mNSCLC and comments on potential strategies for treatment modification.

Zosia Piotrowska, MD, explains how she might treat a patient with EGFR exon 20-mutated mNSCLC who develops an EGFR T790M mutation after mobocertinib treatment.

Joel Neal, MD, presents a second case of a 67-year-old man with no smoking history who was diagnosed with RET-rearranged mNSCLC, while Michelle Shiller, DO, AP/CP, MGP, touches on molecular testing approaches in patients who are suspected of having a RET alteration.

Dr Piotrowska outlines the RET tyrosine kinase inhibitors (TKIs) selpercatinib and pralsetinib, which are available for patients with RET fusion-positive mNSCLC, then Dr Neal follows with a discussion of supporting efficacy data from the LIBRETTO-001 and ARROW trials.

The panel reviews LIBRETTO-001 and ARROW safety data on selpercatinib and pralsetinib in RET fusion-positive mNSCLC, and share their clinical experience in adverse event (AE) management in patients who are receiving one of these therapies.

A focused discussion on whether immunotherapy might be an effective treatment option for patients with RET-positive mNSCLC.

The panel closes by summarizing recent advances in the field and shares hopes for future improvements in molecular testing and treatment options for patients with mNSCLC.