Addition of Dostarlimab to Chemo and Niraparib Maintenance Boosts PFS in Advanced Ovarian Cancer

Ovarian Cancer

The addition of dostarlimab-gxly (Jemperli) to standard-of-care platinum-based chemotherapy and niraparib (Zejula) maintenance, with or without bevacizumab (Avastin), led to a statistically significant improvement in progression-free survival (PFS) compared with chemotherapy followed by niraparib maintenance alone, meeting the primary end point of the phase 3 FIRST trial (NCT03602859).¹

However, regarding the trial’s key secondary end point of overall survival (OS), a statistically significant difference was not observed between the arms.

Safety data were consistent with the known profiles of each agent. Additional analyses are ongoing. Results from the study will be shared with global health authorities and presented at an upcoming medical meeting.

“As part of our focus in gynecological cancers, we continue to evaluate the potential of this combination and look forward to sharing full results from the trial,” Hesham Abdullah, senior vice president and global head, Oncology, R&D, at GSK, stated in a news release.

The international, double-blind, randomized FIRST trial enrolled patients at least 18 years of age with histologically confirmed, high-grade nonmucinous epithelial ovarian, fallopian tube, or peritoneal cancer.²Patients needed to have stage III or IV disease per International Federation of Gynecology and Obstetrics criteria or tumor, node, and metastasis staging criteria. Other key inclusion criteria consisted of adequate organ function; an ECOG performance status of 0 or 1; and normal blood pressure or adequately treated and controlled hypertension. Patients also needed to provide samples for homologous recombinant repair and homologous recombinant deficiency testing.

Key exclusion criteria included mucinous, germ cell, transitional cell, or undifferentiated tumors; low-grade or grade 1 epithelial ovarian cancer; inadequate recovery from prior major surgery; known active central nervous system metastases and/or carcinomatous meningitis; clinically significant cardiovascular disease; and any known history or current diagnosis of myelodysplastic syndrome or acute myeloid leukemia.

Under the original trial protocol, patients were randomly assigned 1:1:2 to receive standard-of-care chemotherapy followed by placebo maintenance; chemotherapy followed by niraparib maintenance; or chemotherapy plus dostarlimab followed by niraparib plus dostarlimab maintenance.¹ Bevacizumab was allowed to be administered to all patients at investigator discretion.

However, the trial’s protocol was amended following approvals of PARP inhibitors in the first-line setting. As such, the chemotherapy plus placebo maintenance arm (n = 193) was closed, and patients were then randomly assigned 1:2 to chemotherapy alone followed by niraparib maintenance alone (n = 385); or chemotherapy plus dostarlimab followed by niraparib plus dostarlimab maintenance (n = 753).

In the experimental arm, patients received dostarlimab at 500 mg once every 3 weeks in cycles 2 to 6, followed by dostarlimab at 1000 mg once every 6 weeks for up to 3 years or until disease progression, unacceptable toxicity, participant withdrawal, or investigator decision; paclitaxel at 175 mg/m² plus carboplatin at area under the curve 5 to 6 mg/mL per min once every 3 weeks for cycles 1 to 6; and niraparib maintenance following the completion of chemotherapy.² Those in the control arm received the same chemotherapy and niraparib regimens along with a dostarlimab placebo. In both arms, bevacizumab could be given at 7.5 or 15 mg/kg once every 3 weeks for a total of 15 months.

The primary end point was PFS for the dostarlimab arm vs chemotherapy alone followed by niraparib maintenance alone. Secondary end points included OS, time to second progression, time to first and second subsequent therapy, overall response rate, duration of response, quality of life, safety, and pharmacokinetics.

References

1. GSK announces FIRST trial met its primary endpoint of progression free survival in first line advanced ovarian cancer. News release. GSK. December 20, 2024. Accessed December 20, 2024. https://www.gsk.com/en-gb/media/press-releases/gsk-announces-first-trial-met-its-primary-endpoint-of-progression-free-survival-in-first-line-advanced-ovarian-cancer/
2. A comparison of platinum-based therapy with TSR-042 and niraparib versus standard of care (SOC) platinum-based therapy as first-line treatment of stage III or IV nonmucinous epithelial ovarian cancer (FIRST). ClinicalTrials.gov. Updated August 16, 2024. Accessed December 20, 2024. https://clinicaltrials.gov/study/NCT03602859