Pembrolizumab Alone or With Chemotherapy for PD-L1–Positive NSCLC?

September 24, 2018
Naveed Saleh, MD, MS

Pembrolizumab plus chemotherapy failed to improve survival compared with pembrolizumab alone in patients with non–small-cell lung cancer.

Researchers found that in patients with non–small-cell lung cancer (NSCLC) and a Tumor Proportion Score (TPS) ≥ 50, pembrolizumab plus chemotherapy failed to improve overall survival (OS) or progression-free survival (PFS) compared with pembrolizumab alone.

Results from the study were presented in a poster presentation at the International Association for the Study of Lung Cancer (IASLC) 19th World Conference on Lung Cancer, held September 23–26 in Toronto.  

Of note, TPS refers to the percentage of viable tumor cells demonstrating partial or complete membrane staining. A specimen is characterized as programmed death ligand 1 (PD-L1) positive if ≥ 50% of viable tumor cells show membrane staining at any intensity.

In the current cross-trial comparison, Doherty et al conducted a network meta-analysis to compare pembrolizumab alone with pembrolizumab plus chemotherapy in NSCLC patients with a TPS score ≥ 50. They assembled an indirect network using the chemotherapy control arms of the KEYNOTE-024 and KEYNOTE-189 trials.

The KEYNOTE trials are well known among experts, according to Paul A. Bunn, Jr, MD, distinguished professor of medical oncology at the University of Colorado.

“In KEYNOTE-024, comparing pembrolizumab to chemotherapy in NSCLC patients of any histology with a TPS score of more than 49, pembrolizumab was superior to chemotherapy,” said Bunn. “In KEYNOTE-189, the combination of pembrolizumab plus chemotherapy was superior to chemotherapy in nonsquamous NSCLC with any TPS score.”

The investigators analyzed baseline characteristics and chemotherapy outcomes in both trials for heterogeneity. They also noted OS, PFS, objective response rate (ORR), and adverse events, including immune-related adverse events.

In total, the researchers included 507 patients in their study, with 154 patients receiving pembrolizumab, 357 patients receiving chemotherapy, and 410 receiving pembrolizumab plus chemotherapy. Baseline characteristics were similar in all patients studied.

The team found that patients in both trials exhibited similar chemotherapy outcomes and thus similar prognoses. They also found no difference between pembrolizumab plus chemotherapy and pembrolizumab alone in terms of OS (hazard ratio [HR], 0.70; 95% CI, 0.38–1.30; P = .26) and PFS (HR, 0.72; 95% CI, 0.45–1.16; P = .18). However, combination therapy was associated with higher ORR (+21.5%; 95% CI, 4.83%–38.2%; P = .011).

Rates of grade 3 to grade 5 adverse events were elevated with combination treatment compared with pembrolizumab alone; however, immune-related adverse events were less frequent with combination treatment.

Bunn reflected on the significance of the current cross-trial comparison in the context of other KEYNOTE trials.

“The conclusion is that one should use pembrolizumab alone for those with TPS > 49 and the combination for those with TPS < 49,” he said. “However, if a patient with high TPS needs a rapid response, the combination can be considered, and, conversely, if the TPS is < 49 and the patient cannot tolerate chemotherapy, pembrolizumab alone is reasonable.”

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