PURPOSE: Platinum-based doublets with concurrent and maintenance bevacizumab are standard therapy for ovarian cancer (OC) relapsing after a platinum-free interval (PFI) >6 months. Immunotherapy may be synergistic with bevacizumab and chemotherapy. PATIENTS AND METHODS: ATALANTE/ENGOT-ov29 (ClinicalTrials.gov identifier: NCT02891824), a placebo-controlled double-blinded randomized phase III trial, enrolled patients with recurrent epithelial OC, one to two previous chemotherapy lines, and PFI >6 months. Eligible patients were randomly assigned 2:1 to atezolizumab (1,200 mg once every 3 weeks or equivalent) or placebo for up to 24 months, combined with bevacizumab and six cycles of chemotherapy doublet, stratified by PFI, PD-L1 status, and chemotherapy regimen. Coprimary end points were investigator-assessed progression-free survival (PFS) in the intention-to-treat (ITT) and PD-L1-positive populations (alpha .025 for each population). RESULTS: Between September 2016 and October 2019, 614 patients were randomly assigned: 410 to atezolizumab and 204 to placebo. Only 38% had PD-L1-positive tumors. After 3 years' median follow-up, the PFS difference between atezolizumab and placebo did not reach statistical significance in the ITT (hazard ratio [HR], 0.83; 95% CI, 0.69 to 0.99; P = .041; median 13.5 v 11.3 months, respectively) or PD-L1-positive (HR, 0.86; 95% CI, 0.63 to 1.16; P = .30; median 15.2 v 13.1 months, respectively) populations. The immature overall survival (OS) HR was 0.81 (95% CI, 0.65 to 1.01; median 35.5 v 30.6 months with atezolizumab v placebo, respectively). Global health-related quality of life did not differ between treatment arms. Grade ≥3 adverse events (AEs) occurred in 88% of atezolizumab-treated and 87% of placebo-treated patients; grade ≥3 AEs typical of immunotherapy were more common with atezolizumab (13% v 8%, respectively). CONCLUSION: ATALANTE/ENGOT-ov29 did not meet its coprimary PFS objectives in the ITT or PD-L1-positive populations. OS follow-up continues. Further research on biopsy samples is warranted to decipher the immunologic landscape of late-relapsing OC.
- MeSH
- antigeny CD274 * terapeutické užití MeSH
- bevacizumab MeSH
- epiteliální ovariální karcinom farmakoterapie MeSH
- kvalita života MeSH
- lidé MeSH
- lokální recidiva nádoru farmakoterapie MeSH
- nádory vaječníků * farmakoterapie patologie MeSH
- platina terapeutické užití MeSH
- protokoly antitumorózní kombinované chemoterapie terapeutické užití MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
PURPOSE OF REVIEW: Epithelial ovarian cancer (EOC) is a prevalent gynecologic malignancy whose prognosis in most cases remains poor despite advances in therapy. In this article, we critically review the available clinical evidence for the choice of first-line chemotherapy in EOC and discuss promising therapeutic strategies. RECENT FINDINGS: In the last 25 years, first-line chemotherapy regimens and the indication of systemic treatment for early-stage disease have been better established. Significant progress has been made in the treatment of advanced EOC with the optimization of the carboplatin plus paclitaxel regimen and the use of intraperitoneal chemotherapy for selected patients. Targeted therapies may be approved for EOC in the near future and this would bring more specific treatments and improve outcomes for patients. Validated biomolecular signatures to better define prognosis and to predict response to therapeutic agents are still lacking. SUMMARY: The standard first-line chemotherapy in EOC is based on the doublet carboplatin plus paclitaxel. It may be possible to improve the efficacy of treatment by means of a more intensive dose-dense regimen or by the intraperitoneal delivery of chemotherapy. Significant improvements in the treatment of EOC are expected from the development of antiangiogenic and other targeted agents and from better patient selection.
- MeSH
- antitumorózní látky terapeutické užití MeSH
- lidé MeSH
- lokální recidiva nádoru farmakoterapie MeSH
- nádory vaječníků farmakoterapie MeSH
- prognóza MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- přehledy MeSH
