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Clinical Trial
. 2021 Jun 10;39(17):1842-1855.
doi: 10.1200/JCO.21.00306. Epub 2021 Apr 23.

Atezolizumab, Bevacizumab, and Chemotherapy for Newly Diagnosed Stage III or IV Ovarian Cancer: Placebo-Controlled Randomized Phase III Trial (IMagyn050/GOG 3015/ENGOT-OV39)

Kathleen N Moore  1   2 , Michael Bookman  3 , Jalid Sehouli  4 , Austin Miller  5 , Charles Anderson  6 , Giovanni Scambia  7 , Tashanna Myers  8 , Cagatay Taskiran  9   10 , Katina Robison  11 , Johanna Mäenpää  12 , Lyndsay Willmott  13 , Nicoletta Colombo  14 , Jessica Thomes-Pepin  15 , Michalis Liontos  16 , Michael A Gold  17 , Yolanda Garcia  18 , Sudarshan K Sharma  19 , Christopher J Darus  20 , Carol Aghajanian  21 , Aikou Okamoto  22 , Xiaohua Wu  23 , Rustem Safin  24 , Fan Wu  25 , Luciana Molinero  26 , Vidya Maiya  26 , Victor K Khor  26 , Yvonne G Lin  26 , Sandro Pignata  27
Affiliations
Clinical Trial

Atezolizumab, Bevacizumab, and Chemotherapy for Newly Diagnosed Stage III or IV Ovarian Cancer: Placebo-Controlled Randomized Phase III Trial (IMagyn050/GOG 3015/ENGOT-OV39)

Kathleen N Moore et al. J Clin Oncol. .

Erratum in

  • Erratum.
    [No authors listed] [No authors listed] J Clin Oncol. 2021 Jul 20;39(21):2420. doi: 10.1200/JCO.21.01441. J Clin Oncol. 2021. PMID: 34265225 Free PMC article. No abstract available.

Abstract

Purpose: To evaluate the addition of the humanized monoclonal antiprogrammed death ligand-1 (PD-L1) antibody, atezolizumab, to platinum-based chemotherapy and bevacizumab in newly diagnosed stage III or IV ovarian cancer (OC).

Methods: This multicenter placebo-controlled double-blind randomized phase III trial (ClinicalTrials.gov identifier: NCT03038100) enrolled patients with newly diagnosed untreated International Federation of Gynecology and Obstetrics (FIGO) stage III or IV OC who either had undergone primary cytoreductive surgery with macroscopic residual disease or were planned to receive neoadjuvant chemotherapy and interval surgery. Patients were stratified by FIGO stage, Eastern Cooperative Oncology Group performance status, tumor immune cell PD-L1 staining, and treatment strategy and randomly assigned 1:1 to receive 3-weekly cycles of atezolizumab 1,200 mg or placebo (day 1, cycles 1-22), with paclitaxel plus carboplatin (day 1, cycles 1-6) plus bevacizumab 15 mg/kg (day 1, cycles 2-22), omitting perioperative bevacizumab in neoadjuvant patients. The co-primary end points were investigator-assessed progression-free survival and overall survival in the intention-to-treat and PD-L1-positive populations.

Results: Between March 8, 2017, and March 26, 2019, 1,301 patients were enrolled. The median progression-free survival was 19.5 versus 18.4 months with atezolizumab versus placebo, respectively (hazard ratio, 0.92; 95% CI, 0.79 to 1.07; stratified log-rank P = .28), in the intention-to-treat population and 20.8 versus 18.5 months, respectively (hazard ratio, 0.80; 95% CI, 0.65 to 0.99; P = .038), in the PD-L1-positive population. The interim (immature) overall survival results showed no significant benefit from atezolizumab. The most common grade 3 or 4 adverse events were neutropenia (21% with atezolizumab v 21% with placebo), hypertension (18% v 20%, respectively), and anemia (12% v 12%).

Conclusion: Current evidence does not support the use of immune checkpoint inhibitors in newly diagnosed OC. Insight from this trial should inform further evaluation of immunotherapy in OC.

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Conflict of interest statement

Kathleen N. MooreHonoraria: Research To Practice, Prime Oncology, Physicans' Education ResourceConsulting or Advisory Role: Genentech/Roche, Immunogen, AstraZeneca, Tesaro, VBL Therapeutics, Merck, Aravive, Pfizer/EMD Serono, Eisai, AbbVie, Vavotar Life Sciences, Mersana, Myriad GeneticsResearch Funding: PTC Therapeutics, Lilly, Merck, Tesaro, Genentech, Clovis Oncology, Lilly Foundation, Regeneron, Advaxis, Bristol-Myers Squibb, Verastem, Novartis Pharmaceuticals UK Ltd, AstraZeneca, Agenus, Takeda, Forty Seven, Stem CentRx, Immunogen, Bayer, Novogen, AbbVie/Stem CentRx Michael BookmanEmployment: The Permanente Medical GroupConsulting or Advisory Role: AstraZeneca, AbbVie, Immunogen, Genentech/Roche, Seattle Genetics, Aravive, Merck Sharp & Dohme Jalid SehouliHonoraria: AstraZeneca, Eisai, Clovis Oncology, Olympus Medical Systems, Johnson & Johnson, PharmaMar, Pfizer, Teva, Tesaro, MSD Oncology, GlaxoSmithKline, BayerConsulting or Advisory Role: AstraZeneca, Clovis Oncology, PharmaMar, Merck, Pfizer, Tesaro, MSD Oncology, Lilly, Novocure, Johnson & Johnson, Roche Diagnostics, Ingress Health, Riemser, Sobi, GlaxoSmithKline, NovartisResearch Funding: AstraZeneca, Clovis Oncology, Merck, Bayer, PharmaMar, Pfizer, Tesaro, MSD Oncology, RocheTravel, Accommodations, Expenses: AstraZeneca, Clovis Oncology, PharmaMar, Roche Pharma AG, Tesaro, MSD Oncology, Olympus Austin MillerUncompensated Relationships: Genentech Giovanni ScambiaConsulting or Advisory Role: Clovis Oncology, AstraZeneca, PharmaMar, Roche, TesaroSpeakers' Bureau: Clovis Oncology, MSD Johanna MäenpääHonoraria: GlaxoSmithKline, AstraZeneca, RocheConsulting or Advisory Role: GlaxoSmithKline, Eisai Europe, AstraZenecaTravel, Accommodations, Expenses: GlaxoSmithKline Lyndsay WillmottHonoraria: Clovis Oncology, AstraZeneca/Merck, Tesaro/GSK, Eisai, Genentech, GlaxoSmithKlineConsulting or Advisory Role: Tesaro/GSK, AstraZeneca/Merck, Clovis Oncology, Eisai, GenentechSpeakers' Bureau: Tesaro/GSK, AstraZeneca/Merck, Clovis Oncology Nicoletta ColomboHonoraria: Roche/Genentech, AstraZeneca, Tesaro, PharmaMar, GlaxoSmithKline, MSD Oncology, Clovis Oncology, Pfizer, Amgen, Immunogen, Novartis, Mersana, Eisai, Merck, Takeda, BiocadConsulting or Advisory Role: Roche/Genentech, PharmaMar, AstraZeneca, Clovis Oncology, Pfizer, MSD Oncology, Tesaro, BioCad, GlaxoSmithKline, Immunogen, Mersana, Eisai, Merck, Takeda, Biocad Michalis LiontosEmployment: Pfizer [I]Stock and Other Ownership Interests: Pfizer [I]Honoraria: MSD Oncology, Roche, Janssen, Sanofi, Bristol-Myers Squibb/Celgene, AstraZeneca, Ipsen, Astellas PharmaConsulting or Advisory Role: Amgen, GlaxoSmithKline, AstraZeneca, JanssenTravel, Accommodations, Expenses: Bayer, Pfizer, Roche, AstraZeneca Yolanda GarciaConsulting or Advisory Role: GlaxoSmithKline/Tesaro, Roche, AstraZenecaSpeakers' Bureau: AstraZenecaResearch Funding: Roche, AstraZenecaTravel, Accommodations, Expenses: GlaxoSmithKline/Tesaro, Roche Christopher J. DarusHonoraria: AstraZenecaConsulting or Advisory Role: AstraZeneca Carol AghajanianConsulting or Advisory Role: Mersana, Eisai, Roche, AbbVie, AstraZeneca/Merck, Roche/Genentech, Repare TherapeuticsResearch Funding: Genentech/Roche, AbbVie, Clovis Oncology, AstraZeneca Aikou OkamotoHonoraria: AstraZeneca Japan, MSD, Chugai Pharma, TakedaConsulting or Advisory Role: AstraZeneca Japan, Chugai PharmaSpeakers' Bureau: AstraZeneca JapanResearch Funding: Kissei Pharmaceutical, Meiji Holdings, Pfizer, Fuji Pharma, Taiho Pharmaceutical, Kaken Pharmaceutical, Chugai Pharma, Tsumura & Co, Daiichi Sankyo Co, Ltd, Shinnihonseiyaku, Mochida Pharmaceutical Co, Ltd, ASKA Pharmaceutical Co, Ltd, Takeda, Terumo Fan WuEmployment: RocheStock and Other Ownership Interests: Roche Luciana MolineroEmployment: GenentechStock and Other Ownership Interests: Roche/GenentechPatents, Royalties, Other Intellectual Property: P35974-US Patent Application Inventorship Vidya MaiyaEmployment: Roche/GenentechStock and Other Ownership Interests: Roche/GenentechTravel, Accommodations, Expenses: Roche/GenentechOther Relationship: Roche/Genentech Victor K. KhorEmployment: Genentech/RocheStock and Other Ownership Interests: Roche, Iovance Biotherapeutics Yvonne G. LinEmployment: Genentech/RocheStock and Other Ownership Interests: Genentech/RocheConsulting or Advisory Role: Venn Biosciences Corporation Sandro PignataHonoraria: AstraZeneca, Roche, PharmaMar, Tesaro, Pfizer, MSD, GlaxoSmithKline, Clovis OncologyConsulting or Advisory Role: AstraZeneca, Roche, PharmaMar, Pfizer, Tesaro, Clovis Oncology, GlaxoSmithKlineResearch Funding: Roche, AstraZeneca, MSD, PfizerNo other potential conflicts of interest were reported.

Figures

FIG 1.
FIG 1.
Trial profile. CP, carboplatin plus paclitaxel.
FIG 2.
FIG 2.
Efficacy: PFS in (A) ITT population and (B) PD-L1+ population; OS in (C) ITT population and (D) PD-L1+ population. CP, carboplatin plus paclitaxel; HR, hazard ratio; ITT, intention-to-treat; NE, not evaluable; OS, overall survival; PD-L1, programmed death ligand-1; PFS, progression-free survival.
FIG 3.
FIG 3.
PFS by subgroup. CP, carboplatin plus paclitaxel; ECOG PS, Eastern Cooperative Oncology Group performance status; HR, hazard ratio; IC, immune cell; NE, not evaluable; PD-L1, programmed death ligand-1; PFS, progression-free survival; TC, tumor cell.
FIG 4.
FIG 4.
PFS in the subgroup of patients with PD-L1: (A) IC ≥ 5% (20% of the ITT population) and (B) TC ≥ 1% (6% of the ITT population). Of note, 67 of the 73 patients with TC ≥ 1% were also PD-L1 IC ≥ 1%. Only six patients whose tumors were identified as PD-L1–positive by TC staining were not considered to have PD-L1–positive tumors by IC staining. aUsing the stratification factors, disease stage, ECOG performance status, and treatment approach. CP, carboplatin plus paclitaxel; ECOG, Eastern Cooperative Oncology Group; HR, hazard ratio; IC, immune cell; ITT, intention-to-treat; NE, not evaluable; PD-L1, programmed death ligand-1; PFS, progression-free survival; TC, tumor cell.
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