Long-Term Data Confirm Survival Benefit for Pembrolizumab in Advanced NSCLC

October 2019, Vol 10, No 5

Chicago, IL—Treatment with the immune checkpoint inhibitor pembroliz­umab (Keytruda) dramatically improved 5-year survival for patients with advanced non–small-cell lung cancer (NSCLC) compared with expected survival in the preimmunotherapy era, according to the 5-year follow-up data from the phase 1b KEYNOTE-001 clinical trial. The study was presented at ASCO 2019 and was published simultaneously in the Journal of Clinical Oncology.1

Before the advent of immunotherapy, the expected 5-year survival rate for patients with advanced NSCLC was 5.5%. In this study, the median overall survival (OS) was 22.3 months for treatment-naïve patients and 10.5 months for previously treated patients. For treatment-naïve patients, the 2-year OS rate was 49%, the 3-year OS rate was 37%, and the 4-year OS rate was 31%. Among previously treated patients, the OS rates were 30.1%, 20.9%, and 18.2%, at 2, 3, and 4 years, respectively.

A PD-L1 tumor proportion score (TPS) of ≥50% was associated with longer OS. For treatment-naïve patients with a TPS of ≥50%, the median OS was 35.4 months and the 5-year OS rate was 29.6%. By contrast, for patients with a PD-L1 score of 1% to 49%, the median OS was 19.5 months and the 5-year survival rate was 15.7%.

For previously treated patients with a PD-L1 score of ≥50%, the median OS was 15.4 months and the 5-year OS rate was 25% compared with 8.5 months and 12.6%, respectively, for patients with a PD-L1 score of 1% to 49%, and 8.6 months and 3.5%, respectively, among patients with a score of <1%.

For 60 patients who received pembrolizumab for 2 or more years, the estimated 5-year survival rate was 78.6% in the treatment-naïve group and 75.8% in the previously treated group.

Patient Survival Extended to ≥5 Years

“These are the longest follow-up data we have on advanced lung cancer patients treated with pembrolizumab. The uniformly negative outlook that has been associated with a diagnosis of advanced non–small-cell lung cancer is certainly no longer appropriate. The fact that we have patients on this trial who are still alive after 7 years is quite remarkable,” said lead author Edward B. Garon, MD, MS, Medical Director, Thoracic Oncology Program, University of California, Los Angeles.

“We also have evidence that most patients who are doing well after 2 years on pembrolizumab live for 5 years or more,” he added.

“These data are encouraging. Taken together with data from other randomized controlled trials, efficacy outcomes and the observed association between PD-L1 expression and overall survival are consistent. The results highlight the potential for long-term benefit that may be realized through individualized treatment selection,” Dr Garon noted.

“These data are similar to what we have seen in other cancers treated with immunotherapy in that there is a population of patients who can live for 5 years or more. It’s truly remarkable that for more patients than ever before, we no longer have to count survival in months,” said ASCO Expert David L. Graham, MD, FACP, FASCO, Levine Cancer Institute, Charlotte, NC.

“We used to have to tell patients their chances down the road were uniformly bad. Now 1 in 4 of them will be around in 5 years. This changes our mindset,” Dr Graham said.

KEYNOTE-001 Study

KEYNOTE-001 enrolled more than 1000 patients, 550 of whom had advanced lung cancer. At ASCO 2019, Dr Garon presented 5-year data on survival for the cohort of patients with lung cancer who were enrolled in the trial. In the context of NSCLC, pembrolizumab is indicated, in combination with pemetrexed and platinum chemotherapy, for first-line treatment of patients with advanced NSCLC and no EGFR or ALK mutations; in combination with carboplatin and either paclitaxel (Taxol) or nab-paclitaxel protein-bound (Abraxane) as first-line treatment for metastatic squamous NSCLC; and as a single agent for first-line treatment of patients with NSCLC that expresses PD-L1.

In the cohort of 550 patients with NSCLC, 449 patients had received previous systemic treatment and 101 were treatment-naïve.

Treatment-related adverse events were reported in 71% of patients. Grades 3 to 5 adverse events occurred in 13% of the patients.

Serious adverse events occurred in 42% of the patients, including 9% with treatment-related serious adverse events. In all, 31 patients discontinued pembro­lizumab because of adverse events, and 9 are still alive (7 in ongoing response). In addition, 2 deaths resulted from treatment-related adverse events, both occurring within the first 32 days of treatment.

The most common immune-mediated adverse events of all grades included hypothyroidism (9%), pneumonitis (5%), and hyperthyroidism (2%). Grades 3 to 5 immune-related adverse events were reported in 4% of the patients.


  1. Garon EB, Hellmann MD, Rizvi NA, et al. Five-year overall survival for patients with advanced non–small-cell lung cancer treated with pembrolizumab: results from the phase I KEYNOTE-001 study. J Clin Oncol. 2019;37:2518-2527.

Related Articles