Pembrolizumab Bests Docetaxel in 5-Year Survival in PD-L1+ Advanced NSCLC

Results from the phase 2/3 KEYNOTE-010 trial continue to favor pembrolizumab, including key survival end points.

After more than 5 years of follow-up for the phase 2/3 KEYNOTE-010 trial (NCT01905657), pembrolizumab (Keytruda) continues to outperform docetaxel as therapy for patients with previously treated, PD-L1–positive advanced non–small cell lung cancer (NSCLC) based on clinically meaningful differences in overall (OS) and progression-free survival (PFS).1

“We continue to see a clinically meaningful improvement in OS and PFS. Five-year rates more than doubled in the pembrolizumab-treated patients for overall survival, compared with those receiving docetaxel,” Roy S. Herbst, MD, PhD, ensign professor of medicine and professor of pharmacology, chief of medical oncology, Yale Cancer Center and Smilow Cancer Hospital, and associate cancer center director for translational research, Yale Cancer Center, said during a virtual presentation of the follow-up results that were presented at the 2020 World Conference on Lung Cancer Singapore.

“Patients who completed 35 cycles or 2 years of experienced durable responses,” he added. The second course of pembrolizumab provided meaningful disease control. Incidents of any grades 3-5 treatment effects were lower with pembrolizumab versus docetaxel. Pembrolizumab monotherapy is a standard of care in patients with immunotherapy-naive or previously treated, PD-L1–positive advanced non-small cell lung cancer.”

Five-year median OS rates were more than doubled with pembrolizumab, compared with docetaxel, in patients with PD-L1 TPS ≥ 50% (25.0% vs 8.2%, respectively) and ≥ 1% (15.6% vs 6.5%). Median OS was superior with pembrolizumab, compared with docetaxel, in patients with PD-L1 TPS ≥ 50% (16.9 months [95% CI, 12.3-21.4] vs 8.2 months [95% CI, 6.4-9.8], respectively; HR, 0.55; 95% CI, 0.44-0.69) and ≥ 1% (11.8 months [95% CI, 10.4-13.1] vs 8.4 months [7.6-9.5]; HR, 0.70; 95% CI, 0.61-0.80).

Median PFS rates were also superior for those with PD-L1 TPS ≥ 50% (5.3 months [95% CI, 4.2-6.5] vs 4.2 months [95% CI, 3.8-5.1]; HR, 0.57; 95% CI, 0.46-0.71) and ≥ 1% (4.0 months [95% CI, 3.1-4.1] vs 4.1 months [95% CI, 3.8-4.5]; HR, 0.84; 95% CI, 0.73-0.96).

In addition, patients who completed 35 cycles or 2 years of treatment with pembrolizumab demonstrated durable clinical benefit, with an overall response rate (ORR) of 98.7%, including 15 complete responses (CRs) and 63 partial responses (PRs). In total, 61 patients (77.2%) were alive at the data cutoff, including 38 patients who were alive without progressive disease (PD). The 3-year OS rate after completing 35 cycles or 2 years was 83.0%.

Twenty-one patients received second-course pembrolizumab. Among those patients, 15 (71.4%) were alive at data cutoff. ORR after starting second-course pembrolizumab was 52.4%, including 1 CR, 10 PRS, and 6 patients with stable disease (SD). Eight patients with a CR, PR, or SD after starting second-course pembrolizumab subsequently had PD.

As of April 8, 2020, the median time from randomization to data cutoff was 67.4 months (range, 60.0-77.9).

In this follow-up analysis, treatment with pembrolizumab continued for 35 cycles (approximately 2 years) or until disease progression or unacceptable toxicity. The analysis included patients who completed pembrolizumab treatment or stopped pembrolizumab after achieving CR. Patients who received ≥6 months of treatment could receive a second course of pembrolizumab for up to 17 cycles (1 year) following disease progression after stopping pembrolizumab. Responses were assessed every 9 weeks, while survival was assessed every 2 months after treatment ended.

The primary end points of the follow-up study were OS and PFS in patients with PD-L1 TPS ≥50% and in those with PD-L1 TPS ≥1%. In the analysis, the pembrolizumab dose groups were pooled.

Previously reported results from the KEYNOTE-010 study (NCT01905657) showed that docetaxel in patients with previously treated advanced NSCLC with PD-L1 TPS ≥50% and ≥1% demonstrated a median OS of 10.4 months with 2 mg/kg pembrolizumab and 12.7 months with 10 mg/kg pembrolizumab, compared with 8.5 months with docetaxel.2

OS was significantly longer in patients treated with 2 mg/kg, compared with docetaxel (HR, 0.71; 95% CI, 0.58-0.88), and in those treated with 10 mg/kg (HR, 0.61; 95% CI, 0.49-0.75; P < .0001).

Those treated with 2 mg/kg and 10 mg/kg pembrolizumab showed a median PFS of 3.9 months and 4.0 months, respectively, compared with 4.0 months with docetaxel.

In patients with PD-L1 TPS ≥50%, OS was significantly longer with 2 mg/kg pembrolizumab, compared with docetaxel (14.9 months vs 8.2 months; HR, 0.54; 95% CI, 0.38-0.77; P = .0002) and with 10 mg/kg pembrolizumab (17.3 months vs 8.2 months; HR, 0.50; 0.36-0.70; P < .0001). PFS was also improved with 2 mg/kg (5.0 months vs 4.1 months; HR, 0.59; 95% CI, 0.44-0.78; P = .0001) and 10 mg/kg pembrolizumab (5.2 months vs 4.1 months; HR, 0.59; 95% CI, 0,45-0.78; P < .0001), compared with docetaxel.

Grade 3-5 treatment-related adverse events were less common with 2 mg/kg (13%) and 10 mg/kg (16%) pembrolizumab than with docetaxel (35%).

In the trial, patients with previously treated advanced NSCLC with PD-L1 TPS ≥1% and were randomized 1:1:1 to receive 2 mg/kg or 10 mg/kg pembrolizumab every 3 weeks (n = 690), or 75 mg/m2 docetaxel every 3 weeks (n = 343).


1. Herbst R, Garon E, Kim D, et al. 5-Year Survival Update From KEYNOTE-010: Pembrolizumab Versus Docetaxel in Previously Treated, PD-L1–Positive Advanced NSCLC. Presented at: 2020 World Conference on Lung Cancer; January 28-31, 2021; Virtual. Abstract FP13.01

2. Herbst R, Baas P, Kim D, et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet. 2015;387:10027. doi:10.1016/S0140-6736(15)01281-7