Niraparib and Dostarlimab Show Improved Progression-Free Survival in First-Line Advanced Ovarian Cancer
GSK recently announced positive results from the phase 3 FIRST-ENGOT-OV44 trial (NCT03602859) investigating the combination of niraparib (Zejula) and dostarlimab-gxly (Jemperli) with standard-of-care (SOC) chemotherapy in patients with first-line advanced ovarian cancer. The trial met its primary endpoint of improved progression-free survival (PFS) compared to SOC chemotherapy alone.
Niraparib/dostarlimab with platinum-therapy met its PFS end point in patients with advanced ovarian cancer in the phase 3 FIRST-ENGOT-OV44 trial.
Though the randomized, double-blind trial demonstrated a significant improvement in PFS, it did not reach statistical significance for the key secondary endpoint of overall survival (OS). Additional analyses are ongoing, and further data will be presented at an upcoming scientific meeting and shared with regulatory authorities.
“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,” said Hesham Abdullah, Senior Vice President and Global Head of Oncology, Research and Development, at GSK, in the press release.
The trial regimen demonstrated a safety and tolerability profile consistent with known safety data for each individual agent.
**Trial Design**
The study enrolled 1,231 patients randomly assigned to 1 of 3 treatment arms:
- Arm 1: SOC chemotherapy followed by placebo maintenance (n=193)
- Arm 2: SOC chemotherapy followed by niraparib maintenance (n=385)
- Arm 3: SOC chemotherapy followed by niraparib and dostarlimab maintenance (n=753)
Bevacizumab (Avastin) could be added to the trial regimen at the investigator’s discretion.
Due to the approval of first-line PARP inhibitors, arm 1 was disbanded, and patients were assigned to either arm 2 or 3.
**Endpoints**
The primary endpoint was PFS, defined as time from treatment randomization to the earlier date of assessment of progression or death by any cause in patients with stage III or IV high-grade nonmucinous epithelial ovarian cancer. Secondary endpoints included OS, quality of life, time to subsequent therapy, objective response rate, duration of response, disease control rate, and safety.
**Eligibility**
Patients were eligible for inclusion if they had a histologically confirmed diagnosis of high-grade stage III or IV nonmucinous epithelial ovarian, fallopian tube, or peritoneal cancer. Other inclusion criteria included adequate organ function, an ECOG performance status of 0 or 1, normal blood pressure, and the ability to take oral medication.
Patients were ineligible if they had mucinous, germ cell, transitional cell, or undifferentiated tumors; low-grade or grade 1 epithelial ovarian cancer; certain pre-existing medical conditions; or known contraindications to the study medications.
**Conclusion**
The FIRST trial results suggest that the combination of niraparib and dostarlimab with SOC chemotherapy may offer a clinically meaningful benefit for patients with first-line advanced ovarian cancer. Further analysis and future data will provide a more complete understanding of the long-term efficacy and safety of this promising approach.
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