KEYNOTE-010 Update Shows ‘Striking’ Durability of Second-Line Pembrolizumab in NSCLC

Pembrolizumab’s benefit in previously treated advanced non–small cell lung cancer (NSCLC) that expresses programmed cell death ligand 1 (PD-L1) is long lasting, persisting even after therapy ends, suggests an update of the KEYNOTE-010 trial.1

Initial results of the randomized phase II/III trial, published after a median follow-up of 13.1 months, showed that pembrolizumab (Keytruda), an immune checkpoint inhibitor that targets programmed cell death protein 1 (PD-1), outperformed docetaxel in terms of overall survival and other efficacy endpoints, with the benefit increasing with the proportion of tumor cells expressing the ligand (PD-L1).2

The update, now after 12 more months of follow-up, showed that pembrolizumab remained superior to docetaxel, reported lead author Roy S. Herbst, MD, PhD, Chief of Medical Oncology and Associate Director for Translational Research at the Yale Cancer Center, New Haven, Connecticut. Moreover, there was an apparent plateauing of the overall survival curves with the immune checkpoint inhibitor, with about one-third of patients still alive.

The clinical benefit of pembrolizumab is durable after 2 years of treatment…. Most patients who complete 2 years of pembrolizumab and stop treatment remain with response, including those patients who have stable disease.
— Roy S. Herbst, MD, PhD

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“With 1 year longer of follow-up, the overall survival benefit of pembrolizumab over docetaxel in previously treated lung cancer patients is maintained,” he commented. “This is the tale of the tail: the tail of the curve [with pembrolizumab], now with more mature data, certainly is out there. It’s real, with greater than 30% of patients with refractory lung cancer surviving at 2 years. So that’s very good to see, with the hazard ratios holding up.”

Analysis of the 47 patients who completed all 2 planned years of pembrolizumab and stopped treatment demonstrated that nearly 90% ultimately had a response. And, although follow-up after stopping treatment was fairly short, only 2 patients (4%) experienced confirmed disease progression during that time.

“The clinical benefit of pembrolizumab is durable after 2 years of treatment…. Most patients who complete 2 years of pembrolizumab and stop treatment remain with response, including those patients who have stable disease,” Dr. Herbst summarized.

“These are certainly very striking results,” he concluded. “At this meeting [2016 World Conference on Lung Cancer], there are many sessions looking at other predictive markers for immunotherapy [besides PD-L1], including genetic and immunohistochemical markers. It will be very important to look at those markers in patients like this, so we can identify who these patients are early on and so others can get combinations.”

Study Details and Findings

Patients enrolled in KEYNOTE-010 came from 24 countries; they had advanced NSCLC with a PD-L1 tumor proportion score (TPS) of at least 1% and had been previously treated with at least one line of chemotherapy. In all, 1,034 patients were randomized evenly to receive pembrolizumab at 2 mg/kg, pembrolizumab at 10 mg/kg, or docetaxel at 75 mg/m2 every 3 weeks.

The updated data showed that median overall survival was 8.6 months with docetaxel, compared with 10.5 months (hazard ratio [HR] = 0.72) with lower-dose pembrolizumab and 13.4 months (HR = 0.60) with higher-dose pembrolizumab, Dr. Herbst reported. The corresponding 2-year overall survival rates were 14.5% vs 30.1% and 37.5%.

Remaining analyses were restricted to the 47 patients who completed the entire planned 2 years of pembrolizumab at either dose and then stopped therapy. Fully 66% of these patients had tumors with at least 50% PD-L1 positivity, compared with 42% of all patients on the trial given pembrolizumab. In this group, the overall response rate was 89%, and the clinical benefit rate was 100%. “Actually, this did not exist when I presented this a year ago, but we now have three complete responders, for 6%,” Dr. Herbst noted.

The median time to response was 2 months (range, 2–24 months); the median duration of response was not reached (range, 2–31 months). A total of 72% of the responses were still ongoing at the time of data cutoff. “The majority of patients who completed 2 years of pembrolizumab were initial responders, having a partial response or complete response,” he pointed out.

Among the 43 evaluable patients with a partial response, the time to response ranged from 2 to 24 months. “As we know, responses usually occur—and it’s quite nice for the patients and for us as clinicians to see this—on the first review. But a number of the responses did occur a bit later, and a few of the responses occurred quite late,” commented Dr. Herbst.

Among the three evaluable patients with a complete response, the pattern was one of an earlier partial response, within 5 months, which gradually evolved over time. In one of these patients, the complete response did not occur until after pembrolizumab had been stopped.

During a median time after stopping therapy of 3.8 months, 2 patients had confirmed disease progression, and another 3 patients had investigator-assessed disease progression. “This is a subject of investigation that certainly our group is interested in—what happens to these patients,” he noted. All 47 patients were alive at data cutoff. ■

Disclosure: Roy S. Herbst, MD, PhD, has been a consultant to AstraZeneca, Eli Lilly, Merck, Pfizer, and Genentech/Roche; has received clinical trials/grant support from Genentech and Merck.


1. Herbst RS, Garon EB, Kim D, et al: KEYNOTE-010: Durable clinical benefit in patients with previously treated, PD-L1-expressing NSCLC who completed pembrolizumab. 2016 World Conference on Lung Cancer. Abstract OA03.07. Presented December 5, 2016.

2. Herbst RS, Baas P, Kim DW, et al: Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): A randomised controlled trial. Lancet 387:1540-1550, 2016.

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