Atezolizumab Misses PFS End Point in Recurrent Epithelial Ovarian Cancer

For patients with recurrent epithelial ovarian cancer, treatment with atezolizumab did not significantly improve progression-free survival (PFS) compared with placebo plus bevacizumab.

These findings, published in the Journal of Clinical Oncology, reflect a missed primary end point of the randomized, double-blinded, phase 3 ATLANTE/ENGOT-ov29 trial. This trial follows several studies of immunotherapy used in first-line patients with ovarian cancer, all of which yielded negative results in terms of statistical significance, though some demonstrated slightly improved results in the treatment arms.

ATLANTE/ENGOT-ov29 included 614 total patients with epithelial ovarian cancer, with 410 randomized to receive atezolizumab and 204 randomized to placebo. Of the full sample, 38% had PD-L1–positive tumors.

Patients in the experimental arm received atezolizumab at doses of 1200 mg or 800 mg for 6 cycles, administered alongside carboplatin plus gemcitabine, paclitaxel, or pegylated liposomal doxorubicin. Meanwhile, the control arm received an identical dose and schedule of placebo, combined with bevacizumab and platinum-based chemotherapy. Beyond evaluating PFS, the study assessed patients for secondary endpoints such as overall survival (OS), time from randomization to second subsequent therapy or date of death (TSST), patient-reported outcomes (PROs), and the frequency of adverse events (AEs).

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After a median follow-up of 3 years, PFS did not reach statistical significance in both the intention-to-treat (ITT) and PD-L1–positive populations.

The median PFS was 13.5 months (95% CI, 12.2-14.2) for the atezolizumab group, while patients treated with placebo plus bevacizumab exhibited a median PFS of 11.3 months (95% CI, 11.0-13.5). With just a 2-month difference, the study authors said this result was not significant in the ITT group (HR, 0.83; 95% CI, 0.69-0.99; P = .041).

The subset of patients with PD-L1-positive tumors included 156 participants in the atezolizumab group and 77 in the placebo group. In this subset, treatment with atezolizumab achieved a median PFS of 15.2 months (95% CI, 13.6-17.3), compared with 13.1 months (95% CI, 11.3-16.5) for placebo plus bevacizumab. Again, with the minor difference, this was deemed insignificant (HR, 0.86; 95% CI, 0.63-1.16; P = .30).

Results pertaining to secondary endpoints indicated that, despite seeing higher figures with atezolizumab treatment, these advantages did not attain statistical significance compared with the control group. For the ITT population, the median TSST was 23.9 months (95% CI, 22.6-26.5) for atezolizumab vs 21.4 months (95% CI, 19.0-24.0) for placebo (HR, 0.81; 95% CI, 0.67-1.01).

Additionally, median OS with atezolizumab reached 35.5 months (95% CI, 32.4-41.3), compared with 30.6 months (95% CI, 27.9-33.6) for placebo (HR, 0.81; 95% CI, 0.65-1.01).

Patients in the atezolizumab arm experienced a similar incidence of grade 3 or higher AEs compared with those in the placebo arm, with 88% of the atezolizumab arm and 87% of the placebo arm experiencing such AEs. Treatment-related grade 3 or higher AEs were observed in 33% of the atezolizumab arm and 35% of the placebo arm. Fatal AEs were reported in 3% of patients treated with atezolizumab and 2% of those in the placebo arm. Among the fatal AEs attributed to atezolizumab were cardiac arrest, peritonitis, and acute myeloid leukemia, while fatal AEs associated with placebo included pulmonary embolism and bowel perforation.

The most commonly observed AE of special interest in the study was hypothyroidism, which occurred in 11% of the atezolizumab group and 5% of the placebo group. In terms of health-related quality of life, there were no discernible differences between the two treatment arms.

While there were no statistically significant differences in PFS, preliminary data indicate a promising signal for OS, which warrants further investigation with extended follow-up. In various cancer types, immunotherapy has demonstrated modest effects on objective response rate and PFS, but it has shown a more substantial impact on OS and long-term PFS. Therefore, one possible critique of the trial is that OS was not initially a co-primary objective, though it was planned for hierarchical testing if either of the PFS co-primary objectives had been achieved.

“As in previous OC [ovarian cancer] trials of immunotherapy, any treatment effect was not immediately apparent, emerging later and with a greater impact on the tail of the curve,” the study authors said. “Final OS results are anticipated in late 2024 and will provide important information on long-term effects in patients potentially deriving sustained benefit from ICIs [immune checkpoint inhibitors].”

Reference

Kurtz JE, Pujade-Laurine E, Oaknin A, et al. Atezolizumab combined with bevacizumab and platinum-based therapy for platinum-sensitive ovarian cancer: placebo-controlled randomized phase III ATALANTE/ENGOT-ov29 trial. Published online August 29, 2023. J Clin Oncol. 2023;JCO2300529. doi:10.1200/JCO.23.00529