Adding low-dose pembrolizumab to chemotherapy results in significant improvements in overall (OS) and progression-free survival (PFS) among patients with advanced non-small cell lung cancer (NSCLC), as shown in a phase 3 trial presented at ASCO 2026.
“In advanced NSCLC … low-dose pembrolizumab significantly improved OS and PFS, [with] benefits seen across all subgroups,” said lead study author Dr Nandini Menon, Tata Memorial Hospital, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India.
Three hundred eighty patients with advanced NSCLC (aged ≥18 years; ECOG PS ≤2) without actionable genomic alterations (AGAs) participated in this phase 3 open-label randomized trial with a superiority design. Of these, 187 were randomized to receive platinum-doublet chemotherapy (arm A) and 193 to platinum-doublet chemotherapy plus low-dose pembrolizumab (arm B).
Chemotherapy consisted of pemetrexed/paclitaxel plus carboplatin/cisplatin for 4‒6 cycles. Participants in arm B received pembrolizumab 50 mg every 3 weeks for the first 4 doses then every 6 weeks. Treatment was administered until disease progression or intolerable adverse effects.
OS was the primary endpoint, while PFS, safety, and quality of life (QoL) were secondary. Menon and her team used the Kaplan-Meier method and Cox proportional hazards model for the analysis.
Most of the patients with advanced NSCLC (median age 57 years) were male (76.1 percent). Of the participants, 61.1 percent had ECOG PS 0‒1 and 38.9 percent had ECOG PS 2. More than half (54.5 percent) of them were former or current smokers. [ASCO 2026, abstract LBA1510]
Adenocarcinoma was the most common histological subtype (68.4 percent) among NSCLC patients, and more than one in four (27.1 percent) had brain metastases.
Improved survival
Over a median follow-up of 13 months, participants in arm A had a median OS of 10.47 months (95 percent confidence interval [CI], 8.38‒12.56), while those in arm B had 13.46 months (95 percent CI, 11.71‒15.22; hazard ratio [HR], 0.72, 95 percent CI, 0.54‒0.95; p=0.020). At 1 year, OS was higher in arm B (57.32 percent, 95 percent CI, 44.93‒65.79) than in arm A (44.4 percent, 95 percent CI, 37.2‒53).
For the secondary outcomes, patients who received low-dose pembrolizumab plus chemotherapy had a median PFS of 6.73 months (95 percent CI, 5.51‒7.96) relative to just 4.70 months (95 percent CI, 4.06‒5.34) among those treated with platinum-doublet chemotherapy (HR, 0.70, 95 percent CI, 0.56‒0.89; p=0.003). PFS at 1 year was 26.72 percent (95 percent CI, 20.23‒35.29) in arm B compared with 18.79 percent (95 percent CI, 13.59‒25.99) in arm A.
In terms of safety, a significantly higher proportion of patients in arm B vs arm A developed grade 3 or higher neutropenia (28 percent vs 17.6 percent; p=0.02), but no difference was noted in the incidence of grade 3 or higher anaemia or thrombocytopenia. Furthermore, 3.1 percent of NSCLC patients treated with low-dose pembrolizumab had grade 3 or higher immune-related pneumonitis.
“The addition of low-dose pembrolizumab to chemotherapy significantly improved OS and PFS in patients with advanced NSCLC, [with] no new safety signals,” Menon said. “This regimen will improve access to immune checkpoint inhibitors (ICIs) in resource-limited settings.”
Pembrolizumab plus platinum doublet chemotherapy is the standard of care for patients with advanced NSCLC without AGAs. However, access to pembrolizumab and other ICIs is limited due to their cost, according to Menon and colleagues.