Lung Cancer

On December 12, 2022, the FDA accelerated the approval of adagrasib (Krazati; Mirati Therapeutics), a RAS GTPase inhibitor, for adults with locally advanced or metastatic non–small-cell lung cancer (NSCLC) and KRAS^G12C mutation (as determined by an FDA-approved test) who have received at least 1 systemic therapy.

On January 26, 2023, the FDA approved pembrolizumab (Keytruda; Merck), a PD-1 inhibitor, as monotherapy for adjuvant treatment of patients with stage IB (T2a ≥4 cm), II, or IIIA non–small-cell lung cancer (NSCLC), after resection and platinum-based chemotherapy.

Two weeks after the initial approval of tremelimumab (Imjudo; AstraZeneca), a CTLA-4 monoclonal antibody, on November 10, 2022, the FDA approved this new immunotherapy, in combination with the PD-L1 inhibitor durvalumab (Imfinzi; AstraZeneca) and platinum-based chemotherapy, for the treatment of adults with metastatic non–small-cell lung cancer (NSCLC) and no EGFR or ALK genomic alterations.

Sotorasib (Lumakras) continues to demonstrate durable efficacy in non–­small-cell lung cancer (NSCLC) with KRAS p.G12C mutation at 2-year follow-up of the phase 2 CodeBreaK 100 clinical trial.

Approximately 13% of patients with lung adenocarcinoma harbor the KRAS p.G12C mutation, which is associated with poor clinical outcomes. During the American Society of Clinical Oncology 2021 virtual annual meeting, Ferdinandos Skoulidis, MD, PhD, MRCP, Assistant Professor, Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, provided updated results from the phase 2 component of the CodeBreaK 100 clinical trial, which evaluated sotorasib (Lumakras), a small-molecule inhibitor of the KRAS p.G12C mutation, in previously treated patients with non–small-cell lung cancer (NSCLC) whose tumors express this aberration. These results were simultaneously published in the New England Journal of Medicine.

Neoadjuvant nivolumab (Opdivo) plus chemotherapy significantly improved pathologic complete response (pCR) rates versus chemotherapy alone in patients with resectable stage IB-IIIA non–small-cell lung cancer (NSCLC), according to final results from the CheckMate-816 clinical trial. These findings were presented by Patrick Forde, MBBCh, Associate Professor of Oncology and Director of the Thoracic Cancer Clinical Research Program at Johns Hopkins University Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, during the virtual 2021 American Association for Cancer Research Annual Meeting.

On September 15, 2021, the FDA accelerated the approval of mobocertinib (Exkivity; Takeda Pharmaceuticals), a tyrosine kinase inhibitor, for the treatment of adults with locally advanced or metastatic non−small-cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations, as detected by the FDA-approved Oncomine Dx Target Test (Life Technologies Corporation), which was approved on the same day as a companion diagnostic for mobocertinib. The FDA granted mobocertinib priority review, breakthrough therapy designation, and orphan drug designation.

Treatment with the immune checkpoint inhibitor atezolizumab (Tecentriq) following surgical resection and chemotherapy significantly improved disease-free survival (DFS) compared with best supportive care (BSC) alone in patients with stage II-IIIA non–small-cell lung cancer (NSCLC) and tumor composite score PD-L1 ≥1%, according to interim results from the phase 3 IMpower010 clinical trial, which were presented at the ASCO 2021 virtual annual meeting.

On May 28, 2021, the FDA accelerated the approval of sotorasib (Lumakras; Amgen), an oral KRAS inhibitor of the RAS GTPase family, for the treatment of adults with locally advanced or metastatic non–small-cell lung cancer (NSCLC) associated with KRAS G12C mutation, as determined by an FDA-approved test, after ≥1 systemic therapies. The FDA granted sotorasib orphan drug and breakthrough therapy designations.

On May 21, 2021, the FDA accelerated the approval of amivantamab-vmjw (Rybrevant; Janssen/Johnson & Johnson), a bispecific antibody targeting mutations in the EGFR and MET pathways, for adults with non–small-cell lung cancer (NSCLC) that is associated with EGFR exon 20 insertion mutations, as detected by the FDA-approved Guardant360 CDx test, which was approved on the same day as a companion diagnostic for amivantamab. The FDA had granted amivantamab a breakthrough therapy designation for this indication.