MSD’s immunotherapy Keytruda (ingredient: pembrolizumab) should be a standard first-line therapy for PD-L1 expressing non-small cell lung cancer (NSCLC), given its curative effects regardless of mutations in SKT11 and KEAP1 genes in a study.

Professor Cho Byoung-chul at Yonsei University Cancer Center claimed so during his oral presentation on the therapeutic effect of Keytruda in association with SKT11 and KEAP1 genetic mutations in the KEYNOTE-042 study, at the virtual meeting of the American Association for Cancer Research (AACR) on Monday.

SKT11 and KEAP1 mutations mostly appear in PD-L1 negative cancer with high tumor mutational burden (TMB). They are known to be associated with resistance to chemotherapy and poor prognosis.

The research team compared Keytruda with platinum-based chemotherapy in PD-L1 positive patients with advanced or metastatic NSCLC in the KEYNOTE-042 study. Then, the team analyzed whole-exome sequencing (WES) data of 429 patients out of 1,274 participants.

The results showed that 33 (7.7 percent) had SKT11 mutation, and 64 (14.9 percent), KEAP1 mutation. Twelve (2.8 percent) had both mutations.

The Keytruda-treated group’s objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were irrelevant to SKT11 and KEAP1 mutations. In contrast, in the chemotherapy group, the drug effect was weaker in patients with SKT11 mutation than in those without it.

“Keytruda monotherapy was associated with better outcomes than chemotherapy regardless of SKT11 or KEAP1 status in PD-L1 positive NSCLC patients,” Cho said.

“While the Keytruda group showed consistent therapeutic effect regardless of SKT11 and KEAP1 mutations, the chemotherapy group had a low drug effect in patients with SKT11 mutation.”

Cho noted that the latest study was a result of exploratory analysis and included only one-third of the participating patients. As SKT11 and KEAP1 mutation frequency was low, researchers should make a careful interpretation of the study, he added.

However, the findings suggest that Keytruda monotherapy should be considered a standard first-line treatment option for advanced PD-L1 positive NSCLC regardless of SKT11 and KEAP1 status, he concluded.

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