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Notably, the median duration of response (DOR) was not reached (range, 9.3 months – not reached). The 6-month DOR rate was 86.4% and the 12-month rate was 66.7%.
“There remains a significant unmet medical need for patients with recurrent or metastatic cervical cancer who progress after chemotherapy containing platinum,” said David O’Malley, MD, division director. Ohio State University Cancer Center Gynecologic Oncology. Arthur G. James Cancer Hospital and Richard J. Solove Research Institute and Professor in the Department of Obstetrics and Gynecology at Ohio State University College of Medicine in Columbus.
“We know that the activity of the PD-1 agent in monotherapy is modest while the inhibition of CTLA-4 shows little or no activity in patients with cervical cancer,” said he added. “Combining anti-PD1 and anti-CTLA-4 [agents] is now an established treatment paradigm for a wide range of solid tumors. In this Phase 2 study design, we report the largest trial to date combining PD-1 and CTLA-4 in patients with cervical cancer.
To be eligible for the trial, patients had to have histologically confirmed squamous cell carcinoma, adenosquamous carcinoma, or cervical adenocarcinoma that recurred after platinum therapy. Patients were also required to have measurable disease and an ECOG performance index of 0 or 1.
The primary endpoint of the trial was ORR by RECIST v1.1 by an independent review committee. Secondary endpoints included OS, DOR, and progression-free survival. The trial enrolled a total of 155 patients in Europe, Australia, South America and the United States.
The median age of the total population was 50 years (range, 24-76). Most of the patients (70.3%) had squamous cell carcinoma, 27.1% had adenocarcinoma and 2.6% had adenosquamous histology. The ECOG performance index was well balanced, 57.4% scored 0 and 42.6% scored 1. A majority of patients (56.8%) had positive, defined PD-L1 tumor expression status. as a combined positive score of at least 1%. The most common past therapeutic exposures, in addition to those containing platinum (99.4%), were taxane (78.7%) and bevacizumab (32.9%).
Balstilimab was administered at a dose of 3 mg / kg every 2 weeks. Zalifrelimab 1 mg / kg was administered every 6 weeks. Treatment lasted up to 24 months and follow-up imaging took place every 6 weeks for 2 years.
At a median follow-up of 21 months, the median PFS was 2.7 months (95% CI: 1.5-3.7). The median OS was 12.8 months (95% CI: 8.8-17.6). In the PD-L1 positive subset, median OS improved at 15.7 months (95% CI: 7.6-21.1).
“Response rates [for this combination] almost double now achieved with second-line approved agents, including single agent PD-1 antibodies, ”noted O’Malley. “Beyond the response rate, the distinguishing feature of the combination of the CTLA-4 and PD-1 antibodies is the improvement in the depth and durability of the responses as well as the survival results. Longer follow-up will hopefully confirm this exciting trend and establish long-term survival as an achievable goal in advanced / recurrent cervical cancer.
In terms of safety, 71.0% of the safety population of 155 patients experienced a treatment-related adverse event (TRAE) of any grade. Common TRAEs of any grade included hypothyroidism (16.8%), diarrhea (14.2%), and fatigue (11.6%). TRAE of at least grade 3 occurred in 20.0% of patients and included an increase in alanine transaminase (2.6%) and diarrhea (1.9%). TRAE leading to dose interruption were reported in 12.3% of patients and TRAE leading to discontinuation occurred in 7.7% of patients.
Immune-mediated AEs were observed less frequently (44.5%) and included hypothyroidism (14.2%), hyperthyroidism (7.1%), diarrhea (7.1%), and puritis ( 4.5%).
“[This was] the largest study to date evaluating PD-1 / CTLA-4 dual checkpoint blockade in patients with recurrent / metastatic cervical cancer, ”concluded O’Malley. “With a median follow-up of almost 2 years, the combination balstilimab and zalifrelimab showed high response rates, long-lasting clinical activity and promising overall survival results. Advocacy results were particularly impressive in PD-L1 positive patients, but also widely seen in subgroups with poor risk characteristics. A phase 2 randomized confirmatory study comparing balstilimab and zalifrelimab with balstilimab alone is being recruited.
Reference
O’Malley DM, Neffa M, Monk BJ, et al. Balstilimab (anti-PD-1) in combination with zalifrelimab (anti-CTLA-4): final results from a phase II study in patients (pts) with cervical cancer (CC) recurrent / metastatic (R / M). Presented at: 2021 Congress of the European Society of Medical Oncology. September 16-21, 2021; virtual. Abstr 724MB.
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