Atezolizumab With Bevacizumab and Nonplatinum Chemotherapy for Recurrent Ovarian Cancer: Final Results From the Placebo-Controlled AGO-OVAR 2.29/ENGOT-ov34 Phase III Trial

Author(s): Philipp Harter, MD^1,2,3; Frederik Marmé, MD^3,4; Andrés Redondo, MD^5,6; Alexander Reuss, MSc^3,7; Kristina Lindemann, MD^8,9,10; Christian Kurzeder, MD^11,12; Els Van Nieuwenhuysen, MD^13,14; Christian Marth, MD^15,16; Klaus Pietzner, MD^3,17; Isabelle Ray-Coquard, MD^18,19; Carmen Garcia-Duran, MD^6,20; Goda Jonuskiene, MD^10,21; Florian Heitz, MD^1,3,17; Charlotte Béllier, MD^19,22; J. Alejandro Pérez-Fidalgo, MD^6,23; Ahmed El-Balat, MD^3,24,25; Frédéric Selle, MD^19,26; Ignacio Romero, MD^6,27; Pauline Wimberger, MD^3,28; Philippe Follana, MD^19,29; Beatriz Pardo, MD^6,30; Nikolaus de Gregorio, MD^3,31,32; Florence Joly, MD^19,33; Lydia Gaba, MD^6,34; Alexander Burges, MD^3,35; Michel Fabbro, MD^19,36; Annette Hasenburg, MD^3,37; Tanja Fehm, MD^3,38; Barbara Schmalfeldt, MD^3,39; Patricia Pautier, MD^19,40;

Source: DOI: 10.1200/JCO-25-01210

Dr. Anjan Patel's Thoughts

This is another well-done study that, frankly, confirms what we’ve seen elsewhere—PDL1 inhibition does not seem to meaningfully change outcomes in platinum-resistant ovarian cancer, even when added to chemo + bev.

PURPOSE

To evaluate atezolizumab combined with bevacizumab and non–platinum-based chemotherapy for recurrent ovarian cancer.

METHODS

The double-blind randomized phase III AGO-OVAR 2.29/ENGOT-ov34 trial (ClinicalTrials.gov identifier: NCT03353831) enrolled patients with first or second relapse of ovarian cancer ≤6 months after completing platinum-based chemotherapy (or third relapse regardless of treatment-free interval). PD-L1 status was tested centrally (VENTANA SP142 assay) in recent (

RESULTS

Among 574 patients randomly assigned between September 2018 and July 2022, 72% were bevacizumab-pretreated, 36% had received three previous treatment lines, 26% had PD-L1–positive tumors, and 54% received paclitaxel with study therapy. After 418 patients had died, the hazard ratio for OS was 0.83 (95% CI, 0.68 to 1.01; P = .06; median 14.2 months with atezolizumab and 13.0 months with placebo) and the hazard ratio for PFS was 0.87 (95% CI, 0.73 to 1.04; P = .12; median 6.4 v 6.7 months, respectively). OS hazard ratios were similar regardless of PD-L1 status. Grade ≥3 adverse events occurred in 72% of atezolizumab-treated and 69% of placebo patients.

CONCLUSION

Combining atezolizumab with bevacizumab and chemotherapy did not significantly improve OS or PFS in patients with recurrent ovarian cancer ineligible for platinum. The safety profile was as expected from previous experience with these drugs.

Author Affiliations

¹Department for Gynecology and Gynecologic Oncology, Evang. Kliniken Essen-Mitte, Essen, Germany; ²Philipps-University of Marburg, Marburg, Germany; ³AGO Study Group, Wiesbaden, Germany; ⁴Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; ⁵Medical Oncology Department, Hospital Universitario La Paz-IdiPAZ, Madrid, Spain; ⁶GEICO, Madrid, Spain; ⁷Coordinating Center for Clinical Trials, Philipps-University of Marburg, Marburg, Germany; ⁸Section for Gynaecologic Oncology, Department of Surgical Oncology, Oslo University Hospital, Oslo, Norway; ⁹Faculty of Medicine, University of Oslo, Oslo, Norway; ¹⁰NSGO-CTU, Copenhagen, Denmark; ¹¹Department for Gynecology and Gynecologic Oncology, University Hospital Basel, Basel, Switzerland; ¹²SAKK, Bern, Switzerland; ¹³UZ Leuven, University Hospitals Leuven, Leuven, Belgium; ¹⁴BGOG, Leuven, Belgium; ¹⁵Department of Gynecology and Obstetrics, Medizinische Universität Innsbruck, Innsbruck, Austria; ¹⁶AGO-Austria, Innsbruck, Austria; ¹⁷Department of Gynecology, Center for Oncological Surgery, Campus Virchow Klinikum, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany; ¹⁸Centre Léon Bérard, University Claude Bernard Lyon, Lyon, France; ¹⁹GINECO, Paris, France; ²⁰Vall d’Hebron Institute of Oncology (VHIO) and Vall d’Hebron University Hospital, Barcelona, Spain; ²¹Vilnius University Hospital Santaros Klinikos, Vilnius, Lithuania; ²²Centre Oscar Lambret, Lille, France; ²³Medical Oncology Department, University Hospital of Valencia, INCLIVA Biomedical Research Institute, CIBERONC, Valencia, Spain; ²⁴Universitätsspital Zürich, Zurich, Switzerland; ²⁵Klinikum der Johann Wolfgang Goethe-Universität Frankfurt, Klinik für Frauenheilkunde und Geburtshilfe, Frankfurt, Germany; ²⁶Groupe Hospitalier Diaconesses, Croix Saint-Simon, Paris, France; ²⁷Fundacion Instituto Valenciano de Oncologia, Valencia, Spain; ²⁸Department of Gynecology and Obstetrics, University Hospital Carl Gustav Carus, TU Dresden and NCT Dresden, Dresden, Germany; ²⁹Centre Antoine Lacassagne, Nice, France; ³⁰Institut Català d’Oncologia (ICO) Duran i Reynals, Barcelona, Spain; ³¹Universitätsklinikum Ulm, Klinik für Frauenheilkunde und Geburtshilfe, Ulm, Germany; ³²SLK-Kliniken Heilbronn GmbH, Frauenklinik, Heilbronn, Germany; ³³Centre François Baclesse, Caen, France; ³⁴Medical Oncology Department, Hospital Clinic and Translational Genomics and Targeted Therapies in Solid Tumors, IDIBAPS, Barcelona, Spain; ³⁵Department of Obstetrics and Gynecology, University Hospital, LMU Munich, Munich, Germany; ³⁶ICM Val d’Aurelle, Montpellier, France; ³⁷Department of Gynecology and Obstetrics, University Medical Center Mainz, Mainz, Germany; ³⁸Klinik für Frauenheilkunde und Geburtshilfe, Universitätsklinikum Düsseldorf, Düsseldorf, Germany; ³⁹Klinik und Poliklinik für Gynäkologie, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany; ⁴⁰Gustave Roussy, Villejuif, France

Efficacy and Safety of Avutometinib ± Defactinib in Recurrent Low-Grade Serous Ovarian Cancer: Primary Analysis of ENGOT-OV60/GOG-3052/RAMP 201

The ENGOT-OV60/GOG-3052/RAMP 201 phase II trial evaluated avutometinib (a RAF/MEK clamp) plus defactinib (FAK inhibitor) in recurrent low-grade serous ovarian cancer (LGSOC), showing a confirmed objective response rate (ORR) of 31% (44% in KRAS-mutant, 17% in KRAS wild-type) and a median progression-free survival (PFS) of 12.9 months (22.0 vs 12.8 months for KRAS-mutant vs wild-type). The median duration of response was notably long at 31.1 months, and the disease control rate was 88%. The most common grade ≥3 AEs were elevated creatine phosphokinase (CPK) (24%), diarrhea (8%), and anemia (5%), with a 10% discontinuation rate due to adverse events (AEs); so management of AE’s is key for using this new drug combo. This combination looks like a real contender for a new standard in recurrent LGSOC, especially for KRAS-mutant patients.

Atezolizumab Combined With Bevacizumab and Platinum-Based Therapy for Platinum-Sensitive Ovarian Cancer: Placebo-Controlled Randomized Phase III ATALANTE/ENGOT-ov29 Trial

Adding Atezo to combination chemotherapy with bevacizumab did not meet the primary end point of PFS. Regardless of the PDL-1 status it was also more toxic. It seems that ovarian cancer is still immune to immunotherapy.

Cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy in patients with advanced ovarian cancer (OVHIPEC-1): final survival analysis of a randomised, controlled, phase 3 trial

The final results from the OVHIPEC1 study confirm a survival benefit in stage III epithelial ovarian cancers. The OS benefit was about 12 months, and the PFS benefit was four months in favor of CRS + HIPEC compared to CRS alone. This should be offered to patients in the context of definitive surgery.

Optimal Treatment Duration of Bevacizumab as Front-Line Therapy for Advanced Ovarian Cancer: AGO-OVAR 17 BOOST/GINECO OV118/ENGOT Ov-15 Open-Label Randomized Phase III Trial

More is NOT better.

Phase III Randomized Trial of Maintenance Taxanes Versus Surveillance in Women With Advanced Ovarian/Tubal/Peritoneal Cancer: A Gynecologic Oncology Group 0212:NRG Oncology Study

In the world of maintenance, Taxanes don’t add survival benefits.