Frontline Pembrolizumab Plus Chemo Shows Promise in Ovarian Cancer

Denise Uyar, MD

First-line platinum-containing chemotherapy plus the anti-PD-1 agent pembrolizumab (Keytruda), followed by pembrolizumab maintenance, appeared feasible and safe for patients with advanced ovarian cancer, preliminary data from a small clinical trial suggested.

Six of 10 patients exhibited no evidence of disease during follow-up for as long as 14 months after debulking surgery, including 1 patient who had suboptimal surgical results.

No new or unexpected adverse events occurred, and no patients developed immune-related adverse events during maintenance therapy. The efficacy of the treatment strategy remains to be determined, Denise Uyar, MD, of the Medical College of Wisconsin in Milwaukee, and colleagues reported in a poster presentation at the 2018 Society of Gynecologic Oncology Annual Meeting.

“Five patients have completed combination therapy and are on maintenance,” the investigators wrote. “One has completed all maintenance therapy. Three patients have progressed to date. One progressed while on combination therapy and 2 while on maintenance therapy.”

The rationale for the combination therapy came from the well-established association between extent of residual disease and long-term outcomes in ovarian cancer. Patients who attain optimal microscopic disease status (no visual residual disease) have better long-term outcomes compared with patients who have optimal macroscopic or suboptimal disease status.

Pembrolizumab has demonstrated single-agent activity in heavily pretreated, PD-L1—positive ovarian cancer, the investigators noted. However, limited data have accumulated regarding the safety and efficacy of combination therapy with carboplatin, a taxane, and pembrolizumab.

Uyar and colleagues reported preliminary findings from a phase II investigator-initiated trial to evaluate the safety and efficacy of first-line combination therapy consisting of carboplatin, a taxane, and pembrolizumab, followed by pembrolizumab, in patients with advanced epithelial ovarian cancer.

Patients with any postoperative residual disease status were eligible for enrollment. Treating physicians had the option of giving patients all 3 drugs on a 21-day schedule or administering paclitaxel on a weekly basis. Treatment continued for a maximum of 6 cycles, followed by maintenance pembrolizumab every 21 days for a maximum of 12 cycles.

Seven of the 10 patients had macroscopically optimal surgical debulking, and the other 3 had suboptimal surgical results. One patient with macroscopically optimal debulking withdrew from the study.

Eight of the 10 patients received pembrolizumab and carboplatin every 21 days plus weekly paclitaxel, and the remaining 2 received all 3 drugs on a 21-day cycle. Five patients completed the combination therapy and initiated pembrolizumab maintenance, completing a cumulative total of 30 cycles.

Grade 3/4 adverse events consisted of neutropenia in 7 patients, anemia in 4, metabolic events in 2, and 1 case each of respiratory, genitourinary, nervous system, and cardiac adverse events. With respect to immune-related adverse events, 1 patient developed grade 4 pneumonitis during adjuvant therapy. No patient had immune-related adverse events during maintenance treatment with pembrolizumab.

Three patients have developed progressive disease, 1 during combination therapy and 2 during maintenance. Two of the 3 patients had suboptimal debulking surgery, and the third had macroscopically optimal debulking. One patient with suboptimal debulking had no evidence of disease 13 months after surgery.

Of the six patients with no evidence of disease, the time from surgery ranged from 3 to 13 months. The 3 patients with progressive disease were 6, 8, and 14 months from surgery.

Uyar D, Bishop EA, Bradley WH, et al. Preliminary data on the use of combination carboplatin, paclitaxel and pembrolizumab therapy for ovarian cancer. Presented at: 2018 SGO Annual Meeting; March 24-27, 2018; New Orleans, LA. Abstract 100.