Outcome of non-small-cell lung cancer with driven mutations treated with anti-PD-(L)1 agents: A systematic review

Area of Science:

• Oncology
• Medical Genetics
• Immunotherapy

Background:

• Patients with EGFR or ALK driver mutations in non-small cell lung cancer (NSCLC) typically benefit from tyrosine kinase inhibitors (TKIs).
• Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, but their efficacy in oncogene-addicted NSCLC remains less understood.
• Limited data exists on ICI activity in NSCLC patients with specific oncogenic driver alterations.

Approach:

• A meta-analysis was conducted on studies reporting ICI activity in oncogene-addicted NSCLC.
• Relevant studies were identified through a comprehensive search of MEDLINE, Cochrane Library, and EMBASE up to January 31, 2021.
• Primary outcomes included median overall survival (OS), with progression-free survival (PFS) and overall response rate (ORR) as secondary endpoints.

Key Points:

• The pooled overall response rate (ORR) for ICIs in EGFR/ALK-mutated NSCLC was 14.5%.
• Median pooled progression-free survival (PFS) was 3.9 months, and median pooled overall survival (OS) was 10.7 months.
• Registration trials showed no significant benefit of second-line immunotherapy for EGFR-mutated or ALK-rearranged NSCLC.

Conclusions:

• Current data suggest that immunotherapy may not be beneficial as a standalone treatment for oncogene-addicted NSCLC.
• Lower tumor mutation burden in these neoplasms may contribute to the limited efficacy of ICIs.
• Further investigation into combination therapies, such as TKIs with ICIs, is warranted to improve outcomes for this patient group.