Checkpoint blockade with the PD-1 inhibitor balstilimab, alone or in combination with the anti-CTLA-4 drug zalifrelimab, showed activity in women with recurrent or metastatic cervical cancer, preliminary results from two phase II trials indicated.
In patients treated with balstilimab alone, the overall response rate (ORR) was 14%, including complete responses in 2%, reported David O’Malley, MD, of the Ohio State University Comprehensive Cancer Center in Columbus.
And in those who received both investigational agents — balstilimab plus zalifrelimab — the ORR increased to 22%, including complete responses in 6%.
“What is really interesting about the combination arm is that while we did see a median duration of response in the single-agent [arm] that was a very impressive 15 months, the duration of response has not been reached in the combination arm,” O’Malley told MedPage Today.
He said that the tripling of the complete response rate as well as the better duration of response suggest that combination immunotherapy may be “the future of cervical cancer treatment.”
Each of the studies involved women with recurrent or metastatic cervical cancer from cancer centers across the U.S. and Europe who previously received platinum-based chemotherapy as first-line treatment.
“These are the two largest trials of immunotherapy in recurrent metastatic cervical cancer that have been reported thus far,” he said.
In the single agent trial, 160 women were given balstilimab at 3 mg/kg every 2 weeks, while in the second trial balstilimab was evaluated in 155 women at the same dosage in combination with zalifrelimab at a dose of 1 mg/kg every 6 weeks. Findings from the trials were recently presented by O’Malley at the 2020 European Society for Medical Oncology virtual congress.
O’Malley emphasized that in both trials there were responders who were PD-L1 negative. In the single agent trial the ORRs were 19% for those with PD-L1-positive disease and 10% for those with PD-L1-negative disease, while in the combination trial those rates were 27% and 11%, respectively.
Furthermore, O’Malley noted, when broken down by histology, the ORR was higher in patients with squamous cell carcinoma who received the combination therapy (27% vs 18% with balstilimab alone), while the ORRs were higher with single-agent balstilimab for patients with adenocarcinoma, adenosquamous, or other histology (8% vs 5% with the combination).
Histology may be a main predictor of response rather than PD-L1 status, O’Malley suggested.
“We reported similar response rates in our squamous cell carcinoma patients as we saw in the PD-L1-positive patients,” he said. “But when we looked at the adenocarcinoma and adenosquamous patients, we saw the rates were similar to PD-L1-negative patients. This calls into question whether the better predictor of response is histology rather than PD-L1 status, and that may be something to look at in the future.”
Regarding a comparison of balstilimab with pembrolizumab (Keytruda), O’Malley pointed out that pembrolizumab has only been approved for women with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1.
“We know that these drugs are more similar than they are different,” he said. “We obviously don’t have a direct comparison between balstilimab and pembrolizumab, but with balstilimab we are seeing clear response rates, though modest, in patients who are in the PD-L1-negative group.”
As for toxicity, O’Malley said balstilimab’s profile was comparable to pembrolizumab. Patients in the combination study did experience more immune-related adverse effects than in the single-agent study. For example, patients on balstilimab-zalifrelimab experienced more gastrointestinal disorders, endocrine disorders, and laboratory abnormalities than those on balstilimab alone. “But it is still a reasonable toxicity profile,” he said.
O’Malley reported relationships with Agenus, Ambry, Amgen, Abbvie, Cordgenics, Genentech/Roche, AstraZeneca, Clovis Oncology, Eisai, Merck, Tesaro, GlaxoSmithKline, Iovance, Immunogen, GOG-Foundation, Janssen/J&J, LEAP Therapeutics, Mersana, Myriad, Novocure, Regeneron, TapImmune/Marker Therapeutics, Tarveda, Seattle Genetics, GenMab, Advaxis, VentiRx, Array Biopharma, EMD Serono, Ergomed, Ajinomoto, Ludwig Cancer Research, Stemcentrx, Cerulean Pharma, Bristol Myers Squibb, Serono, TRACON Pharmaceuticals, INC Research, inVentiv Health Clinical, and PRA International.