Tony S.K. Mok, MD, BMSc, FRCPC, FASCO, highlights novel partners and potential new approaches for immunotherapy-based regimens for the treatment of patients with non–small cell lung cancer.
Deborah B. Doroshow, MD, PhD, discusses the efficacy and toxicity profiles of pralsetinib and selpercatinib and how they influence treatment selection for patients with RET fusion–positive non–small cell lung cancer, and provides insight on several areas of ongoing or potential research in lung cancer.
Edward S. Kim, MD, MBA, discusses necessary changes that would make cancer research more accessible to patients in community settings, multidisciplinary efforts that should take place at every step of the trial design and implementation process, and how future clinical trials should be intentional about the patient demographics.
Immunotherapy administered alone or in combination with chemotherapy has become the standard of care across advanced non–small cell lung cancer in several settings, with continued effort devoted to further enhancing and improving upon these treatments.
New agents in development including ABBV-011 and BL-B01D1 seek to turn the tides of relapsed extensive-stage small cell lung cancer; although chemoimmunotherapy has earned its right as the frontline standard of care, both classes of agents have yet to demonstrate benefit in second or later lines.
Positive event-free survival data from the phase 3 AEGEAN, NEOTORCH, and KEYNOTE-671 trials add further evidence to the benefit of perioperative immunotherapy in early-stage non–small cell lung cancer but have yet to show clear biomarkers of response beyond PD-L1.
Pasi A. Jänne, MD, PhD, details common EGFR mutations in NSCLC, the importance of testing for EGFR mutations in all patients, the clinical implications of overall survival data for adjuvant osimertinib from the ADAURA trial, and ongoing trials examining combination therapies to potentially improve upon the use of single-agent osimertinib.
Jonathan Wesley Riess, MD, MS, discusses a phase 1 trial examining the combination of sapanisertib and telaglenastat, and explains why glutaminase inhibition is being investigated as a novel way to treat select patients with non–small cell lung cancer.
Leveraging EGFR TKIs as a backbone for combination therapies will be pivotal for expanding treatment options and delivering more personalized therapies in the first-line setting for patients with non–small cell lung cancer harboring EGFR mutations.
PD-L1 and tumor mutational burden are established biomarkers for leveraging immunotherapy in non–small cell lung cancer; however, their use may not be appropriate in determining treatment decisions for all patients.
With two highly selective and active RET inhibitors approved for use in patients with metastatic RET alteration–positive non–small cell lung cancer, the dilemma is not determining which agent to select but ensuring that next-generation sequencing is done up front and in the presence of acquired resistance.
Antibody-drug conjugates have demonstrated substantial activity in patients with HER2-mutated non–small cell lung cancer, with fam-trastuzumab deruxtecan-nxki showcasing the strongest response rate and progression-free survival benefit to date.
Traditional predictive biomarkers for the efficacy of peri-operative immunotherapy for patients with advanced non–small cell lung cancer, such as PD-L1 expression, still hold value but newer biomarker candidates such as minimal residual disease are starting to make an impact.