Pembrolizumab’s Indication for the Treatment of SCLC in the US Is Withdrawn

Merck, the manufacturer of pembrolizumab, announced that it would be withdrawing the agent’s indication for the treatment of patients with previously treated SCLC.

The PD-1 inhibitor pembrolizumab (Keytruda) has been voluntarily withdrawn for its indication in patients with metastatic small cell lung cancer (SCLC) after at least 2 prior lines of therapy by its manufacturer, Merck.1

The decision to withdraw the agent for use in this patient population was done in conjunction with the FDA and does not affect indications for pembrolizumab in other diseases.

Pembrolizumab was initially granted accelerated approval in 2019 for patients with SCLC following disease progression on or after frontline platinum-based chemotherapy and at least 1 other therapy.2 Efficacy was based on results from the phase 1 KEYNOTE-28 (NCT02054806) and the phase 2 KEYNOTE-158 (NCT02628067) trials. Treated patients received either intravenous (IV) pembrolizumab at 200 mg every 3 weeks (n = 64) or 10 mg/kg every 2 weeks (n = 19).

The main efficacy outcomes in 83 total patients treated in the supporting trials were objective response rate (19%; 95% CI, 11%-29%) and rate of durable responses at 6 (94%), 12 (63%), and 18 months (56%) in the 16 responders.

In January 2020, Merck announced that the confirmatory phase 3 KEYNOTE-604 trial (NCT03066778) met 1 of its dual primary end points of progression-free survival (PFS) but failed to demonstrate a statistically significant benefit in overall survival (OS).3

“Results of KEYNOTE-604 demonstrated the potential of [pembrolizumab], in combination with chemotherapy, to improve outcomes for patients newly diagnosed with extensive-stage small cell lung cancer [ES-SCLC], a highly aggressive malignancy,” Roy Baynes, MD, PhD, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories, said in a press release when the results were announced.

Patients on the trial were being treated for ES-SCLC in the frontline setting with pembrolizumab plus chemotherapy of etoposide plus either carboplatin or cisplatin versus chemotherapy alone. The combination arm resulted in a statistically significant improvement in PFS compared with the control arm (HR, 0.75; 95% CI, 0.61-0.91; P = .0023), with medians of 4.5 and 4.3 months, respectively. Rates of PFS at 12 months were 13.6% and 3.1%, respectively.4

Although the combination was able to produce a numerically longer median OS, at 10.8 months versus 9.7 months with chemotherapy, the hazard ratio for survival was nonsignificant at 0.80 (95% CI, 0.64-0.98). Rates of OS at 12 months were 45.1% and 39.6%, respectively, and 22.5% and 11.2% at 24 months.

“The accelerated pathways created by the FDA have been integral to the remarkable progress in oncology care over the past 5 years and have helped many cancer patients with advanced disease, including small cell lung cancer, access new treatments,” Baynes said. “[Pembrolizumab] remains a foundational treatment for certain patients with metastatic non-small cell lung cancer. We will continue to rigorously evaluate the benefits of [pembrolizumab] in small cell lung cancer and other types of cancer, in pursuit of Merck’s mission to save and improve lives.”

The consultation with the FDA is part of an industry-wide assessment of indications from accelerated approval that have not met requirements of confirmation. As part of this withdrawal, Merck will contact health care providers nationwide; patients and their providers who are currently using pembrolizumab for this indication should discuss best options for treatment going forward.


1. Merck provides update on Keytruda (pembrolizumab) indication in metastatic small cell lung cancer in the US. News release. Merck. March 2, 2021. Accessed March 2, 2021.

2. FDA approves pembrolizumab for metastatic small cell lung cancer. FDA. June 17, 2019. Accessed March 2, 2021.

3. Merck’s Keytruda (pembrolizumab) in combination with chemotherapy significantly improved progression-free survival compared to chemotherapy alone as first-line treatment for extensive stage small cell lung cancer. News release. Merck. January 6, 2020. Accessed March 2, 2021.

4. Rudin CM, Awad MM, Navarro A, et al; KEYNOTE-604 Investigators. pembrolizumab or placebo plus etoposide and platinum as first-line therapy for extensive-stage small-cell lung cancer: randomized, double-blind, phase III KEYNOTE-604 study. J Clin Oncol. 2020;38(21):2369-2379. doi:10.1200/JCO.20.00793.

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