1423MO - End-of-study analysis from JACOB: A phase III study of pertuzumab (P) + trastuzumab (H) and chemotherapy (CT) in HER2-positive metastatic gastric or gastro-esophageal junction cancer (mGC/GEJC)

Background

In JACOB (NCT01774786), a double-blind, placebo-controlled, randomised, multicentre, phase III study in patients (pts) with HER2-positive mGC/GEJC, addition of P to H + CT did not significantly improve overall survival (OS) v placebo (PLA) at >24.4 months (m) median follow-up; median OS: 17.5 m with P + H + CT v 14.2 m with PLA + H + CT, HR 0.84 (95% CI 0.71, 1.00); p=0.057 (Tabernero et al. Lancet Oncology 2018). Here we report the end-of-study analysis at >44.4 m median follow-up.

Methods

Pts with previously untreated disease were randomised 1:1 to P + H + CT or PLA + H + CT. P (840 mg) + H (8 mg/kg loading and 6 mg/kg maintenance doses) were given intravenously every 3 weeks until disease progression or unacceptable toxicity. CT was a standard cisplatin/fluoropyrimidine regimen. The primary endpoint was OS. Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), duration of response (DoR) and safety. All results are considered descriptive.

Results

The date of this database lock snapshot was 24 Jan 2020. Overall, 388 pts were randomised to P + H + CT v 392 to PLA + H + CT (intention-to-treat population). Efficacy / safety results are shown in the Table. Table: 1423MO

The incidence of symptomatic left ventricular systolic dysfunction / heart failure was low and similar in both arms (P + H + CT: 0.8%; PLA + H + CT: 0.3%). The incidence of all-grade diarrhoea was higher in the P + H + CT arm (62.6% v 35.8% in the PLA + H + CT arm); the majority of events were grade 1 or 2 in severity.

Conclusions

The end-of-study analysis from JACOB confirmed evidence of treatment activity, with a 15% reduction in risk of death when adding P to H + CT in previously untreated pts with mGC/GEJC. The overall safety profile of P + H + CT was considered acceptable.

Clinical trial identification

NCT01774786.

Editorial acknowledgement

Support for third-party writing assistance for this abstract, furnished by Islay Steele, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland.

Legal entity responsible for the study

F. Hoffmann-La Roche Ltd.

Funding

F. Hoffmann-La Roche Ltd.

Disclosure

J. Tabernero: Advisory/Consultancy: Scientific consultancy role for Array Biopharma, AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, Chugai, Genentech, Inc., Genmab A/S, Halozyme, Imugene Limited, Inflection Biosciences Limited, Ipsen, Kura Oncology, Lilly, MSD, Menarini, Merck Serono; Advisory/Consultancy: Scientific consultancy role for Merrimack, Merus, Molecular Partners, Novartis, Peptomyc, Pfizer, Pharmacyclics, ProteoDesign SL, Rafael Pharmaceuticals, F. Hoffmann-La Roche Ltd, Sanofi, SeaGen, Seattle Genetics, Servier, Symphogen, Taiho, VCN Bioscience; Advisory/Consultancy: Scientific consultancy role for Biocartis, Foundation Medicine, HalioDX SAS and Roche Diagnostics; Non-remunerated activity/ies, F. Hoffmann-La Roche Ltd – Third-party editing assistance: F. Hoffmann-La Roche, Basel, Switzerland. P.M. Hoff: Non-remunerated activity/ies, F. Hoffmann-La Roche Ltd – Third-party editing assistance: F. Hoffmann-La Roche, Basel, Switzerland; Research grant/Funding (self): F. Hoffmann-La Roche Ltd. L. Shen: Non-remunerated activity/ies, F. Hoffmann-La Roche Ltd – Third-party editing assistance: F. Hoffmann-La Roche, Basel, Switzerland; Research grant/Funding (self): F. Hoffmann-La Roche Ltd; Advisory/Consultancy: F. Hoffmann-La Roche Ltd. A. Ohtsu: Research grant/Funding (self): BMS; Non-remunerated activity/ies, F. Hoffmann-La Roche Ltd – Third-party editing assistance: F. Hoffmann-La Roche, Basel, Switzerland; Non-remunerated activity/ies: Personal fees from BMS, Ono, Taiho and Chugai. M.A. Shah: Non-remunerated activity/ies, F. Hoffmann-La Roche Ltd – Third-party editing assistance: F. Hoffmann-La Roche, Basel, Switzerland; Research grant/Funding (self): Astellas, Merck, Boston Biomedical. A. Siddiqui: Full/Part-time employment: Roche Products Limited; Non-remunerated activity/ies, F. Hoffmann-La Roche Ltd – Third-party editing assistance: F. Hoffmann-La Roche, Basel, Switzerland. S. Heeson: Shareholder/Stockholder/Stock options: F. Hoffman-La Roche Ltd; Full/Part-time employment: Roche Products Limited; Non-remunerated activity/ies, F. Hoffmann-La Roche Ltd – Third-party editing assistance: F. Hoffmann-La Roche, Basel, Switzerland. H. Wu: Shareholder/Stockholder/Stock options: F. Hoffman-La Roche Ltd; Full/Part-time employment: Roche (China) Holding Ltd; Non-remunerated activity/ies, F. Hoffmann-La Roche Ltd – Third-party editing assistance: F. Hoffmann-La Roche, Basel, Switzerland. E. Restuccia: Shareholder/Stockholder/Stock options, Full/Part-time employment: F. Hoffmann-La Roche, Basel, Switzerland; Non-remunerated activity/ies, F. Hoffmann-La Roche Ltd – Third-party editing assistance: F. Hoffmann-La Roche, Basel, Switzerland. Y-K. Kang: Advisory/Consultancy: Taiho, Ono, Merck, Daehwa, BMS, Astellas, Zymeworks, Alx Oncology, Amgen, Novartis, Macrogenics, Surface Oncology; Non-remunerated activity/ies, F. Hoffmann-La Roche Ltd – Third-party editing assistance: F. Hoffmann-La Roche, Basel, Switzerland.