As reported in The Lancet Oncology by Bradley J. Monk, MD, and colleagues, the phase III CALLA trial showed no significant improvement in progression-free survival with the addition of durvalumab to chemoradiotherapy in previously untreated patients with locally advanced cervical cancer.

Bradley J. Monk, MD

Study Details

The double-blind trial included 770 women from sites in 15 countries. They were randomly assigned between February 2019 and December 2020 to receive durvalumab at 1,500 mg every 4 weeks (n = 385) or placebo (n = 385) with and following chemoradiotherapy for up to 24 cycles. Chemoradiotherapy consisted of 45 Gy of external-beam radiotherapy at 5 fractions per week concurrent with cisplatin at 40 mg/m² or carboplatin at AUC 2 once weekly for 5 weeks, followed by image-guided brachytherapy (high-dose rate = 27.5–30 Gy; low-dose/pulse-dose rate = 35–40 Gy).

Most patients were from Central and South America (46% and 43% in the two groups) and Central and East Asia (39% and 37%). The primary endpoint of the trial was investigator-assessed progression-free survival in the intent-to-treat population.

Progression-Free Survival

Median follow-up was 18.5 months (interquartile range [IQR] = 13.2–21.5 months) in the durvalumab group and 18.4 months (IQR = 13.2–23.7 months) in the control group. At data cutoff, progression-free survival events had occurred in 112 patients in the durvalumab group vs 128 in the control group. Median progression-free survival was not reached (95% confidence interval [CI] = not reached to not reached) in either group; the hazard ratio nonsignificantly favored the durvalumab group (0.84, 95% CI = 0.65–1.08, P = .17). Rates at 12 and 24 months were 76.0% vs 73.3% and 65.9% vs 62.1%, respectively.

Among 706 patients with PD-L1 expression (tumor area positivity score) ≥ 1%, the hazard ratio for the durvalumab group vs the control group was 0.83 (95% CI = 0.64–1.09). Among 369 patients with PD-L1 expression ≥ 20%, the hazard ratio was 0.62 (95% CI = 0.42–0.91).

Adverse Events

Grade 3 or 4 adverse events occurred in 52% of patients in the durvalumab group vs 51% of those in the control group, with the most common in both groups being anemia (20% vs 15%) and decreased white blood cells (10% vs 13%). Serious adverse events occurred in 28% vs 23% of patients.

Five treatment-related deaths occurred in the durvalumab group, consisting of urinary tract infection, blood loss anemia, and pulmonary embolism related to chemoradiotherapy only, endocrine disorder related to durvalumab only, and sepsis related to both durvalumab and chemoradiotherapy. One treatment-related death occurred in the control group, consisting of pneumonia related to chemoradiotherapy.

The investigators concluded, “Durvalumab concurrent with chemoradiotherapy was well tolerated in participants with locally advanced cervical cancer; however, it did not significantly improve progression-free survival in a biomarker unselected, all-comers population. Concurrent durvalumab plus chemoradiotherapy warrants further exploration in patients with high tumoral PD-L1 expression. Rigorous monitoring ensured high chemoradiotherapy compliance with advanced technology and allowed patients to receive optimal care.”

Dr. Monk, of HonorHealth Research Institute, University of Arizona College of Medicine, Phoenix, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by AstraZeneca. For full disclosures of the study authors, visit thelancet.com.