Pembrolizumab Added to Chemotherapy Improves PFS in Endometrial Cancer

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Adding pembrolizumab to standard chemotherapy led to significantly longer progression-free survival (PFS) rates vs chemotherapy alone among patients with advanced or recurrent endometrial cancer, according to findings from the phase 3 NRG-GY018 trial (NCT03914612).¹

Currently, paclitaxel plus carboplatin is the standard first-line chemotherapy for patients with endometrial cancer. However, the benefit of adding pembrolizumab to standard of care chemotherapy remains unclear. To assess the potential benefit of the addition of pembrolizumab, a double-blind, placebo-controlled, randomized, phase 3 trial was initiated, which included 816 patients with measurable disease (stage III or IVA) or stage IVB or recurrent endometrial cancer.

Findings from the study showed that at the 12-month analysis, Kaplan–Meier estimates of PFS in the mismatch repair-deficient (dMMR) cohort (n = 225) were 74% among those given pembrolizumab and 38% for those treated with placebo (HR, 0.30; 95% CI, 0.19-0.48; P <.001), a 70% difference in relative risk. In the mismatch repair-proficient (pMMR) cohort (n = 588), the median PFS was 13.1 months with pembrolizumab and 8.7 months with placebo (HR, 0.54; 95% CI, 0.41-0.71; P <.001).

There were no unexpected adverse events (AEs) observed among patients given pembrolizumab and combination chemotherapy. Grade 3 or greater adverse events were seen more in patients treated with pembrolizumab in both the dMMR (63.3% v 55.1%) and pMMR cohorts (47.2% v 45.3%).

“The main findings were an improvement in the progression-free and overall survival for the addition of pembrolizumab to standard chemotherapy with acceptable toxicity,” said Matthew Powell, MD, chief, division of Gynecologic Oncology, Washington University School of Medicine, and US principal investigator of the RUBY trial, told Targeted Oncology^TM.

In the phase 3 trial, patients were randomized in a 1:1 ratio to receive pembrolizumab or placebo along with combination therapy with paclitaxel plus carboplatin.² Pembrolizumab or placebo was given in 6 cycles every 3 weeks, followed by up to 14 maintenance cycles every 6 weeks.

Once enrolled in the study, patients were stratified into 2 cohorts: dMMR or pMMr disease. Patients aged 18 years and older with measurable stage III, IVA, IVB, or recurrent endometrial cancer were eligible for enrollment if they had a pathology report showing results of institutional MMR IHC testing, and a histologic confirmation of the original primary tumor. Patients who had previously received adjuvant chemotherapy were permitted in the study if the treatment-free interval was at least 12 months.

The primary end point of the study was PFS, and secondary end points also measured safety, and other efficacy measures, including objective response rate, duration of response, and overall survival.

Overall, both cohorts of the study showed that the addition of pembrolizumab to chemotherapy significantly improved PFS and no unexpected adverse events occurred.¹ Further studies plan to assess the combination further to determine whether it is more efficacious than pembrolizumab alone in this patient population.

“The next steps are to further understand the effects in the MMR-proficient population and what additional can be added to improve outcomes such as anti-VEGF therapy.We will also study if just immunotherapy alone may be enough for patients with dMMR tumors,” concluded Powell.

REFERENCES

1. Eskander RN, Sill MW, Beffa L, et al. Pembrolizumab plus chemotherapy in advanced endometrial cancer. N Engl J Med. 2023;388(23):2159-2170. doi:10.1056/NEJMoa2302312

2. Testing the addition of the immunotherapy drug pembrolizumab to the usual chemotherapy treatment (paclitaxel and carboplatin) in stage III-IV or recurrent endometrial cancer. ClinicalTrials.gov. Updated May 16, 2023. Accessed August 30, 2023. https://clinicaltrials.gov/study/NCT03914612