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Pembrolizumab Plus Chemotherapy Phase III Study Shows Mixed Results in SCLC

Nichole Tucker
Published Online:10:00 PM, Wed January 8, 2020
The combination of pembrolizumab (Keytruda) and chemotherapy improved progression-free survival (PFS) in patients with small cell lung cancer (SCLC) compared with chemotherapy alone, meeting 1 of the primary end points of the phase III KEYNOTE-604 study, according to a press release from pembrolizumab developer, Merck. Compared with a chemotherapy regimen of either etoposide plus cisplatin or cisplatin alone, the PFS improvement with pembrolizumab was significant (HR, 0.75; 95% CI, 0.61-0.91).

However, the pre-specified end point of overall survival (OS), did not meet statistical significance (HR, 0.80; 95% CI, 0.64-0.98).The detailed results will be presented at an upcoming medical conference and will also be discussed with regulatory organizations.

“Results of KEYNOTE-604 demonstrated the potential of Keytruda, in combination with chemotherapy, to improve outcomes for patients newly diagnosed with extensive stage 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 statement.

In the randomized, double-blind, placebo-controlled phase III trial (NCT03066778) patients received either a 21-day cycle of pembrolizumab 200 mg on day 1 plus etoposide 100 mg/m2 on days 1, 2, and 3 along with the investigator’s choice of platinum-based chemotherapy, or an equivalent dosage of placebo plus etoposide for 21 days. The study evaluated multiple secondary end points, including objective response rate, duration of response (DOR), and quality of life.

To be eligible to enroll in the study, patients were required to be newly diagnosed with SCLC by histology or cytology, have extensive-stage disease, and 1 or more measurable lesions. They also had to have an ECOG performance status of 0 or 1, a life expectancy of at least 3 months, and adequate liver function. Participants were also required to provide archival tumor samples or newly obtained core or excisional biopsy of their non-irradiated tumor lesion.

Individuals who had prior systemic therapy for SCLC, prior anti–PD-1 or anti–PD-L1 therapy, a live vaccine within 30 days prior to the first dose of study treatment, or major surgery within 3 weeks of study recruitment were excluded. Patients with certain conditions that may interfere with pembrolizumab or chemotherapy were also excluded. 

In June of 2019, pembrolizumab was granted FDA approval for the treatment of patients with metastatic SCLC who had disease progression on or after platinum-based chemotherapy and at least 1 other prior line of therapy. The approval was based on KEYNOTE-158 (cohort G) and KEYNOTE-028 (cohort C1), which showed that pembrolizumab had an ORR of 19% (95% CI, 11%-29%), which included a complete response rate of 2% and a partial response rate of 17%. Additionally, a DOR of 94% of the 16 responding patients who responded to treatment had a 6-month DOR. A 12-month or longer DOR was also observed in 63% of patients, and an 18-month DOR was observed in 56% of patients.
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]. Kenilworth, New Jersey: Merck; January 6, 2020. https://bwnews.pr/2T8ovOH. Accessed January 8, 2020.

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