Immunotherapy may best be kept as a third option for patients with non-small cell lung cancer (NSCLC) and actionable driver mutations, according to the conclusions from a recent retrospective study.1

The study evaluated 551 patients from 10 countries who received immune checkpoint inhibitor (ICI) monotherapy for advanced NSCLC who had at least 1 driver mutation. The study found a wide range of responses to treatment with ICI, varying from 0% in patients with ALK mutations to 26% in patients with KRAS mutations.

Overall, outcomes for those patients with EGFR, ALK, or ROS1 mutations were inferior to those seen in patients with a KRAS mutations, indicating that ICI should “only be considered after exhaustion of targeted therapies, and in some cases, potentially in all other therapies including standard and salvage chemotherapies,” according to the researchers.

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The majority of patients had adenocarcinoma and the study included patients with KRAS (271 individuals), EGFR (125 individuals), BRAF (43 individuals; [V600E, 17 individuals; other, 18 individuals]), MET (36 individuals [MET amplification 13 individuals; exon 14-skipping mutation, 23 individuals]), HER2 (29 individuals), ALK (23 individuals), RET (16 individuals), ROS1 (7 individuals), and multiple drivers (1 individual).

The overall rate of partial or complete response was 19%. Outside of those with a KRAS mutation, the best response rate for patients harboring all other driver mutations was 12.7%.

Median progression-free survival was 2.8 months. Long-term responders were more frequent in KRAS (12-month progression-free survival: 25.6%), MET (12-month progression-free survival: 23.4%), and BRAF (12-month progression-free survival: 18.0%) than in other subgroups.

“We think that there are 2 ways to optimize the use of immunotherapy in the context of oncogenic addiction,” the researchers wrote. “The first one is to combine immunotherapy with other drugs such as chemotherapy and anti-angiogenic agents. The second one is to identify new relevant biomarkers besides PD-L1 expression and [tumor mutational burden] considering the complex molecular biology of NSCLC.”


  1. Mazières J, Drilon A, Lusque A, et al. Immune checkpoint inhibitors for patients with advanced lung cancer and oncogenic driver alterations: results from the IMMUNOTARGET registry [published online May 24, 2019]. Ann Oncol. doi: 10.1093/annonc/mdz167