Durvalumab Plus CRT Fails to Meet PFS End Point in High-Risk Locally Advanced Cervical Cancer

The results of the global phase 3 CALLA trial (NCT03830866) that were read out at the 2022 Annual Global Meeting of the International Gynecologic Cancer Society (IGCS) demonstrated that durvalumab (Imfinzi) plus chemoradiotherapy (CRT) failed to meet the primary end point of significantly improved progression-free survival (PFS) compared with CRT and placebo among patients with high-risk locally advanced cervical cancer, and that future research is necessary for improving patient outcomes, according to presenter Bradley Monk, MD, FACS, FACOG.

The 12-month PFS rate for durvalumab plus CRT was 76.0% compared with 73.3% following placebo plus CRT. The 24-month PFS rate was 65.9% for the durvalumab plus CRT arm vs 62.1% in the placebo plus CRT arm (Hazard ratio [HR], 0.84; 95% CI, 0.65-1.08; P = .174). The median follow-up in both groups was 18.5 months vs 18.4 months, respectively. Moreover, Monk detailed the findings of the study’s subgroup analysis.

“[In the] hypothesis-generating subgroups, you can see the confidence intervals are broad, but the patients at highest risk of progression and death, specifically the lymph node–positive stage III group had a HR of 0.71,” Monk said during a presentation on the findings. “This still did not reach the 0.65 target HR. In the aortic node subset, the HR was 0.60.”

A total of 770 patients across 15 countries and 120 sites enrolled in the CALLA trial and were randomly assigned 1:1 to either 1500 mg of durvalumab every 4 weeks for 24 doses or matched placebo, both of which were followed by 40 mg of cisplatin, 45 Gy of external body radiotherapy in 25 fractions, and high dose brachytherapy at 27.5 Gys to 30 Gys or a low dose of 35.0 to 40 Gys. The trial included patients who were 18 years and older with histologically confirmed cervical adenocarcinoma, squamous carcinoma, or adenosquamous carcinoma. Patients also needed to have high-risk locally advanced cervical cancer that was either node positive with stage IB2 to IIB disease or stages IIIA to IVA with any node status. An ECOG performance status of 0 or 1 was also required.

Key secondary end points included overall survival (OS), objective response rate (ORR), duration of response (DOR), and safety and tolerability.

The median patient age was 50 years for the durvalumab plus CRT arm and 48 years for the placebo plus CRT arm. Across both arms, most patients were Hispanic/Latino, White, or Asian. In both the experimental arm and control arm, respectively, the most common countries of origin included Latin America (45.7% vs 42.9%), Asia (39.2% vs 37.4%), United State/Europe (10.4% vs 14.3%), and Russia (4.4% vs 5.2%).

At a median follow-up of 20.4 months vs 20.3 months in the experimental and control arm, respectively, the median OS was not mature (HR, 0.78; 95% CI, 0.55-1.10; P = .156). Other findings indicated that the ORR was 82.6% in the durvalumab arm, which included a complete response rate of 42.9% and a partial response rate of 39.7%. Comparatively, the rates in the placebo arm were 80.5%, 40.3%, and 40.3%, respectively. The 12-month localized disease progression rate was 8.2% in the durvalumab arm vs 8.2% in the placebo arm and the 24-month rates were 13.1% and 12.7%, respectively. In terms of distant disease progression, the 12-month rate was 12.3% in the experimental arm vs 15.7% in the control arm, and at 24 months the rates were 16.1% and 21.0%, respectively.

A total of 16.9% of patients in the durvalumab group experienced adverse effects (AEs) that led to treatment discontinuation compared with 13% of patients in the placebo group. Grade 3/4 AEs occurred in 51.7% of patients in the durvalumab group and 51.0% of patients in the placebo group. Serious AEs occurred in 27.5% and 23.2% of patients, respectively. The most common immune-related AE was hypothyroidism, which occurred in 15.1% of patients in the durvalumab group and 4.7% of patients in the placebo group.Other common AEs in the experimental arm and control arm, respectively, were anemia (56.6% vs 54.4%), nausea 55.3% vs 52.3%), diarrhea (45.7% vs 49.5%), vomiting (27.3% vs 27.6%), and urinary tract infection (25.7% vs 24.5%).

Reference

Monk, B, Toita T, Wu X, et al. Durvalumab, in combination with and following chemotherapy, in locally advanced cervical cancer: results from the phase 3 international, randomized, double-blind, placebo-controlled CALLA trial. Presented at: 2022 International Gynecologic Cancer Society Annual Meeting; September 29-October 1, 2022; New York, NY. Abstract O001. Accessed September 29, 2022.