Chemotherapy Plus Pembrolizumab Significantly Improves Outcomes in Advanced Lung Cancer

Pembrolizumab plus standard first-line chemotherapy was found to significantly improve response rates and progression-free survival in treatment-naïve advanced non-small cell lung cancer (NSCLC) patients.

This PD-1 inhibitor is part of a class of checkpoint inhibitors, which target the mechanism the tumor uses to shut down the body’s immune response.

“Pembrolizumab enables T cells to reactivate and accomplish what they are designed to do — facilitate tumor cell killing,” said principal study investigator Corey Langer.

Researchers conducted a phase 2 KEYNOTE-021 study using 123 patients with stage 3B/4, chemotherapy-naïve, nonsquamous NSCLC. Participants were randomized to receive 4 cycles of carboplatin and pemetrexed (500-mg/m2 every 3 weeks), with or without 24 months of treatment with pembrolizumab (200-mg every 3 weeks). There was a median follow-up of 10.6 months.

At the median follow-up, the results of the study showed that patients in the pembrolizumab plus chemotherapy arm had a significantly greater objective response rate compared with patients in the chemotherapy alone arm (55% versus 29%, P=0.0016).

Although patients were not chosen by the amount of PD-L1 expression in their tumor, researchers did find a higher response rate of about 80% for the pembrolizumab plus chemotherapy combination in tumors with PD-L1 expression greater than or equal to 50%. Researchers also observed an improved progression-free survival of patients who received pembrolizumab (median 13 months versus 8.9 months).

However, overall survival rates were found to be similar between the 2 arms (6-month survival rate = 92%).

“This is the first randomized phase 2 trial in advanced, treatment-naïve non-squamous non-small cell lung cancer to assess the benefit of adding a monoclonal antibody targeting PD-1 to standard chemotherapy,” Langer said. “If these benefits are confirmed in an ongoing phase 3 trial, the results may radically alter the treatment paradigm in advanced non-small cell lung cancer.”

In regards to adverse events (AEs) of grade 3 severity or above, there was a higher incidence in the pembrolizumab arm (39%) compared with the chemotherapy alone arm (26%). However, it had no impact on treatment discontinuation rates or treatment-related deaths.

The most common treatment-related AEs were fatigue and nausea, which was most common in the pembrolizumab group, and anemia, which was more common in the chemotherapy alone group.

“Data for the combination of chemotherapy plus pembrolizumab in this population is certainly encouraging, and it is reassuring to see that the addition of pembrolizumab to first-line chemotherapy has a manageable toxicity profile and doesn’t increase the incidence of treatment-related adverse events or deaths,” said researcher Raffaele Califano. “Notably, the progression-free survival reported in the standard arm was much longer than expected and nearly doubled when compared to historical data, which could be due to patient selection or other clinical/molecular characteristics of the patients enrolled in this study.

“In order to establish if this strategy should be adopted in clinical practice, these results should be investigated further in a phase 3 randomized study with a similar design, adequately powered for progression-free survival and with robust assessment of patient’s reported outcomes.”