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B7-H1/PD-1 blockade therapy in non-small cell lung cancer: current status and future direction
Scott Gettinger1, Roy S Herbst
1From Yale School of Medicine, Yale Comprehensive Cancer Center, New Haven, CT.
Abstract:
Over the past few years, there has been a mounting enthusiasm around the potential of immunotherapy in the treatment of non-small cell lung cancer (NSCLC). This interest was catalyzed in 2012 by initial reports of responses to programmed death 1 (PD-1) pathway inhibition in patients with heavily pretreated advanced NSCLC. Since then, a number of antibodies targeting either PD-1 or the primary ligand of PD-1, programmed death ligand 1 (PD-L1), have shown durable responses in phase I studies with large NSCLC expansion cohorts. Therapies have been well tolerated, with rare severe autoimmune toxicity. Two phase III trials have completed accrual in pretreated NSCLC patients, with a phase III trial underway in chemotherapy-naive patients with advanced NSCLC. Efforts are now focusing on identifying predictive biomarkers such as tumor PD-L1 expression and combinations of PD-1/PD-L1 inhibitors with either standard therapies for advanced NSCLC or other immunotherapies. This review summarizes clinical trial results to date and discusses challenges with ongoing and future clinical trials evaluating this new class of drugs.
Insights
Immunotherapy targeting the programmed death 1 (PD-1) pathway shows durable responses in advanced non-small cell lung cancer (NSCLC). Ongoing trials explore biomarkers and combinations for this well-tolerated treatment.
Area of Science:
- Oncology
- Immunology
Background:
- Immunotherapy, particularly targeting the programmed death 1 (PD-1) pathway, has emerged as a promising treatment for non-small cell lung cancer (NSCLC).
- Initial reports in 2012 demonstrated responses to PD-1 pathway inhibition in advanced NSCLC patients, catalyzing further research.
Purpose of the Study:
- To review clinical trial results of PD-1/PD-L1 inhibitors in NSCLC.
- To discuss challenges and future directions for immunotherapy trials in NSCLC.
Main Methods:
- Review of clinical trial data, including phase I, II, and III studies of PD-1 and PD-L1 inhibitors.
- Analysis of response rates, tolerability, and biomarker investigations.
Main Results:
- Antibodies targeting PD-1 or PD-L1 have demonstrated durable responses in phase I NSCLC studies.
- These therapies are generally well-tolerated, with infrequent severe autoimmune toxicity.
- Phase III trials are ongoing or completed in both pretreated and chemotherapy-naive advanced NSCLC patients.
Conclusions:
- PD-1/PD-L1 pathway inhibition represents a significant advancement in NSCLC treatment.
- Future research focuses on predictive biomarkers, such as tumor PD-L1 expression, and combination therapies.
