Pembrolizumab Combo Yields Meaningful PFS Benefit in Cervical Cancer

"These results are very encouraging and support the use of pembrolizumab combined with the current standard of care in locally advanced cervical cancer to help address the need for new treatment options beyond chemoradiotherapy alone," according to Domenica Lorusso, MD, PhD, lead investigator at the European Network of Gynaecological Oncological Trial (ENGOT) groups, and associate professor of Obstetrics and Gynecology at the Catholic University of Rome.

Combining pembrolizumab (Keytruda) with external beam radiotherapy (EBRT), concurrent chemotherapy, and brachytherapy produced a statistically significant and clinically meaningful improvement in progression-free survival (PFS) vs concurrent chemoradiotherapy alone in those with high-risk locally advanced cervical cancer, according to a press release on interim data from the phase 3 KEYNOTE-A18 trial (NCT04221945).

Investigators also observed a favorable trend in overall survival (OS) among patients in the pembrolizumab plus concurrent chemoradiotherapy arm, although these data were not mature as of the interim analysis. Additionally, treatment with pembrolizumab did not raise any new safety signals in the trial. Investigators look to share their findings at a future medical meeting and submit their data to regulatory authorities.

“Patients with high-risk locally advanced cervical cancer often have a poor prognosis, with more than half of patients experiencing disease recurrence within 2 years,” Domenica Lorusso, MD, PhD, lead investigator at the European Network of Gynaecological Oncological Trial (ENGOT) groups, and associate professor of Obstetrics and Gynecology at the Catholic University of Rome, said in the press release. “However, there have been limited new treatment advances for these patients beyond the current standard of care in the last 20 years. These results are very encouraging and support the use of pembrolizumab combined with the current standard of care in locally advanced cervical cancer to help address the need for new treatment options beyond chemoradiotherapy alone.”

In the double-blind phase 3 KEYNOTE A-18/ENGOT-cx11/GOG-3047 trial, investigators are assessing pembrolizumab plus EBRT and concurrent cisplatin followed by brachytherapy vs placebo plus concurrent chemoradiotherapy in patients with high-risk locally advanced cervical cancer.

Patients were randomly assigned to receive 200 mg of pembrolizumab or placebo intravenously on day 1 of each 3-week cycle for 5 cycles followed by 400 mg of pembrolizumab or placebo once every 6 weeks for an additional 15 cycles. All patients received concurrent cisplatin at 40 mg/m² intravenously once a week followed by EBRT and brachytherapy as 90 Gy for volume-directed and 75 Gy for point-directed treatment.

The primary end points of the trial are PFS and OS. Secondary end points include objective response rate, complete response rate, and safety.

Patients 18 years and older with International Federation of Gynecology and Obstetrics (FIGO) 2014 stage IB2 to IIB or stage III to IVA disease were eligible for enrollment on the trial. Additional eligibility criteria included having no receipt of definitive surgical, radiation, or systemic therapy for cervical cancer; an ECOG performance status of 0 or 1; providing a tissue sample from a core incisional or excisional biopsy of a tumor lesion; radiographically evaluable disease; and adequate organ function.

Those with FIGO 2014 stage IVB disease or previous receipt of hysterectomy were unable to enroll on the trial. Patients were also unsuitable for enrollment if they received a live vaccine within 30 days of study entry or prior systemic anti-cancer therapy within 4 weeks of randomization, had a contraindication to cisplatin, or had active autoimmune disease requiring systemic therapy within the past 2 years. Having an active infection requiring systemic therapy or evidence of metastatic disease per RECIST v1.1 criteria in the inguinal region were also grounds for exclusion.

“We are encouraged by these results that show treatment with [pembrolizumab] significantly improved [PFS] for patients with newly diagnosed high-risk locally advanced cervical cancer,” Gursel Aktan, MD, PhD, vice president of global clinical development at Merck Research Laboratories, concluded.

Reference

Merck announces phase 3 KEYNOTE-A18 trial met primary endpoint of progression-free survival (PFS) in patients with newly diagnosed high-risk locally advanced cervical cancer. News release. Merck. July 19, 2023. Accessed July 19, 2023. https://shorturl.at/qxFR2