Response to First-Line Pembrolizumab in Metastatic KRAS-Mutated Non-Small-Cell Lung Cancer

Abstract

Aims:

This retrospective study aims to identify a possible predictive role of KRAS mutations in non-small-cell lung cancer in response to first-line pembrolizumab, either as monotherapy or combined with chemotherapy.

Methods:

Patients received pembrolizumab alone (n = 213) or associated with chemotherapy (n = 81).

Results:

A mutation in the KRAS gene was detected in 27% of patients. In patients on pembrolizumab alone, median progression-free survival in KRAS-mutated cases was longer than in wild-type cases (11.3 vs 4.4 months; p = 0.019), whereas median overall survival did not reach statistical significance (22.1 vs 12.5 months; p = 0.119). Patients receiving chemo-immunotherapy with KRAS-positive tumors had a similar progression-free survival (9.7 vs 7.3 months; p = 0.435); overall survival data were immature.

Conclusion:

This study suggests a correlation between KRAS status and response to pembrolizumab.

Keywords::

• combination therapy
• KRAS
• NSCLC
• pembrolizumab
• predictive factors

Author contributions

Study conception and design: S Rossi, A Santoro; collection and interpretation of data: all authors; statistical analysis: L Giordano; manuscript drafting: S Rossi; manuscript editing: all authors; approval to submit for publication: all authors.

Acknowledgments

Editorial assistance was provided by Aashni Shah (Polistudium Srl, Milan, Italy).

Financial disclosure

The authors have no financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, stock ownership or options and expert testimony.

Writing disclosure

Medical writing support was provided by Aashni Shah and was funded by internal funds.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval from the local ethics committee of IRCCS Humanitas Research Hospital or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations.

In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.