The addition of pembrolizumab to carboplatin and pemetrexed improves overall response rate compared with chemotherapy alone and has a manageable safety profile in patients with newly diagnosed advanced nonsquamous non-small cell lung cancer (NSCLC), according to a study published in The Lancet Oncology.1

Because the impact of adding a third agent to platinum-doublet chemotherapy in the first-line treatment setting of patients with advanced NSCLC remains unclear, researchers sought to assess the activity and tolerability of pembrolizumab, carboplatin, and pemetrexed in this patient population.

For the phase 2 cohort of the open-label, multicohort KEYNOTE-021 study ( Identifier: NCT02039674), investigators enrolled 123 chemotherapy-naïve patients with stage IIIB or IV, nonsquamous NSCLC without targetable EGFR or ALK mutations. Participants were randomly assigned to receive 4 cycles of pembrolizumab plus platinum-doublet chemotherapy followed by pembrolizumab for 24 months and indefinite pemetrexed maintenance therapy or 4 cycles of chemotherapy followed by pemetrexed maintenance.

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Results showed that 55% (95% CI, 42-68) of the 60 patients treated with chemoimmunotherapy achieved an objective response compared with 29% (95% CI, 18-41) of patients treated with chemotherapy alone (P =.0016).

Researchers found that the incidence of grade 3 or worse treatment-related adverse events was similar between the 2 treatment arms, with the most common grade 3 or worse treatment-related adverse events in the pembrolizumab group being anemia and decreased neutrophil count.

In the chemotherapy only arm, the most frequently reported grade 3 or worse adverse events were anemia, decreased neutrophil count, pancytopenia, and thrombocytopenia.

Of note, 1 patient treated with pembrolizumab and chemotherapy experienced a treatment-related death due to sepsis vs 2 deaths in the chemotherapy arm due to sepsis and pancytopenia.

The findings ultimately suggest that the chemoimmunotherapeutic combination could be an effective and tolerable first-line treatment strategy for patients with advanced nonsquamous NSCLC. Researchers are further exploring the efficacy of this regimen in an ongoing, international, double-blind, phase 3 trial.


1. Langer CJ, Gadgeel SM, Borghaei H, et al. Carboplatin and pemetrexed with or without pembrolizumab for advanced, non-squamous non-small-cell lung cancer: a randomised, phase 2 cohort of the open-label KEYNOTE-021 study. Lancet Oncol. 2016 Oct 10. doi: 10.1016/S1470-2045(16)30498-3. [Epub ahead of print]