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The Efficacy of Immune Checkpoint Inhibitors vs. Chemotherapy for KRAS-Mutant or EGFR-Mutant Non-Small-Cell Lung

Wei Chen1, Ling Li1, Sheng Cheng1

  • 1Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing, China.

Disease Markers
|September 5, 2022
PubMed
Abstract

Insights

Immune checkpoint inhibitors improve survival in non-small-cell lung cancer (NSCLC) with KRAS mutations. Combination therapy shows promise for EGFR-mutant NSCLC, while PD-L1/PD-1 inhibitors benefit EGFR wild-type NSCLC.

Area of Science:

  • Oncology
  • Immunotherapy
  • Genetics

Background:

  • Non-small-cell lung cancer (NSCLC) treatment strategies are evolving, particularly for patients with specific genetic mutations like KRAS and EGFR.
  • Immune checkpoint inhibitors (ICIs) have emerged as a significant therapeutic option, but their comparative effectiveness against traditional chemotherapy requires detailed assessment in distinct molecular subtypes.

Purpose of the Study:

  • To compare the efficacy of immune checkpoint inhibitors versus chemotherapy in patients with KRAS-mutant or EGFR-mutant non-small-cell lung cancer.
  • To evaluate the impact of ICIs on overall survival (OS) and progression-free survival (PFS) in different NSCLC molecular subtypes.

Main Methods:

  • A systematic meta-analysis of randomized controlled trials (RCTs) was conducted, searching Cochrane Library, PubMed, Web of Science, and Embase up to February 19, 2022.
  • Nine clinical trials involving 5633 NSCLC participants were included.
  • Progression-free survival (PFS) and overall survival (OS) were the primary outcome measures, analyzed using Review Manager Software (RevMan version 5.4).

Main Results:

  • Immune checkpoint inhibitors significantly extended OS and PFS in patients with EGFR wild-type NSCLC compared to chemotherapy alone.
  • For EGFR-mutant NSCLC, PD-L1/PD-1 inhibitors combined with chemotherapy improved PFS compared to chemotherapy alone.
  • In NSCLC patients with KRAS mutations, ICIs demonstrated superior OS and PFS compared to chemotherapy, with a notable PFS benefit for KRAS G12C mutations.

Conclusions:

  • Patients with EGFR wild-type NSCLC and those with KRAS mutations may benefit from PD-L1/PD-1 inhibitors.
  • Combination therapy with PD-L1/PD-1 inhibitors and chemotherapy appears more effective than chemotherapy alone for EGFR-mutant NSCLC.
  • ICIs represent a promising therapeutic avenue for specific molecular subtypes of NSCLC, warranting further investigation.

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