Clinical Outcomes of PD-1/PD-L1 Inhibitors Among Patients With Advanced or Metastatic Non–Small Cell Lung Cancer With BRAF, ERBB2/HER2, MET, or RET Alterations: A Systematic Literature Review

Abstract

The therapeutic landscape for patients with advanced or metastatic non–small cell lung cancer (NSCLC) is rapidly evolving due to advances in molecular testing and the development of new targeted therapies and immunotherapies. However, the efficacy of programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors in advanced or metastatic patients with NSCLC whose tumors harbor BRAF V600E mutation, HER2/ERBB2 alteration, MET exon 14 skipping mutation, or RET rearrangement is not completely understood. A systematic literature review was performed to summarize evidence from clinical trials and observational studies on objective response rate, progression-free survival, and overall survival in patients whose tumors express these biomarkers and who were treated with PD-1/PD-L1 inhibitors. Searches of Embase, MEDLINE, conference abstracts, and a clinical trial registry identified a total of 12 unique studies: 4 studies included patients with BRAF V600E mutation, 6 studies included patients with HER2/ERBB2 alteration, 7 studies included patients with MET exon 14 skipping mutation, and 5 studies included patients with RET rearrangement. Across studies, there was heterogeneity in treatment and patient characteristics and a lack of reporting on many important predictive and prognostic factors, including treatment regimens, patients’ line of therapy, and tumor PD-L1 expression, which may explain the wide variation in objective response rate, progression-free survival, and overall survival across studies. Therefore, additional studies prospectively evaluating clinical outcomes of PD-1/PD-L1 inhibitors among patients with advanced or metastatic NSCLC whose tumors harbor emerging predictive or prognostic biomarkers are needed to determine whether this class of immunotherapy can provide additional survival benefits for these patients.

Efficacy and safety of anlotinib in combination with immune checkpoint inhibitors or not as advanced non-small cell lung cancer treatment: a systematic review and network meta-analysis

“…For advanced NSCLC, third-line anlotinib significantly improved median PFS and OS versus placebo. Anlotinib may also confer superior survival over other TKIs ( 6 ). Some evidence indicates TKIs could impact the immune microenvironment and enhance immune responses.…”

“…For ICIs, particularly antibodies targeting programmed cell death protein 1 (anti-PD-1) and programmed death ligand 1 (anti-PD-L1), can reinvigorate cytotoxic CD8 + T cells by blocking PD-1 on activated T cells and PD-L1 on tumor cells, thus harnessing adaptive immunity against NSCLC. In unresectable NSCLC, ICIs have been shown to improve overall survival (OS) and progression-free survival (PFS) following chemoradiation, becoming standard of care ( 6 - 8 ). Interestingly, recent studies demonstrate ICIs also confer improved survival in resectable NSCLC ( 8 ).…”