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Clinical Outcomes of PD-1/PD-L1 Inhibitors Among Patients With Advanced or Metastatic Non-Small Cell Lung Cancer With
Katherine G Akers1, Sabine Oskar2, Bin Zhao2
1PRECISIONheor, New York, NY.
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.
Insights
Efficacy of PD-1/PD-L1 inhibitors for advanced non-small cell lung cancer (NSCLC) with specific mutations (BRAF, HER2, MET, RET) remains unclear. Further research is needed to determine survival benefits for these patients.
Area of Science:
- Oncology
- Immunotherapy
- Molecular Diagnostics
Background:
- The treatment of advanced or metastatic non-small cell lung cancer (NSCLC) is evolving with targeted therapies and immunotherapies.
- The effectiveness of programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors in NSCLC patients with specific genetic alterations (BRAF V600E, HER2/ERBB2, MET exon 14 skipping, RET rearrangement) requires further investigation.
Approach:
- A systematic literature review was conducted to synthesize evidence from clinical trials and observational studies.
- Searches included Embase, MEDLINE, conference abstracts, and a clinical trial registry, identifying 12 unique studies.
- Studies focused on objective response rate, progression-free survival, and overall survival in patients treated with PD-1/PD-L1 inhibitors.
Key Points:
- Evidence was found for BRAF V600E (4 studies), HER2/ERBB2 (6 studies), MET exon 14 skipping (7 studies), and RET rearrangement (5 studies).
- Significant heterogeneity in treatment and patient characteristics was observed across studies.
- Inconsistent reporting of predictive/prognostic factors (e.g., treatment regimens, line of therapy, PD-L1 expression) complicates interpretation.
Conclusions:
- Variations in outcomes across studies may be attributed to heterogeneity and lack of detailed reporting.
- Prospective studies are essential to evaluate PD-1/PD-L1 inhibitor outcomes in advanced NSCLC with emerging biomarkers.
- Further research is needed to confirm survival benefits of immunotherapy for these specific patient populations.
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