Plain Language Summary
What is this summary about?
This is a plain language summary of a study called ATTRACTION-4. In this study, researchers looked at the effects of a medication called nivolumab, which can boost anti-tumor immunity. Asian people with cancer of the stomach or the junction where the food pipe joins the stomach (called gastroesophageal junction) that had spread to other parts of the body (called advanced cancer) or came back after surgery (called recurrent cancer), and could not be removed by surgery joined the study. Only people whose cancer did not produce a protein called HER2 (known as HER2-negative cancer) could take part in the study.
The researchers wanted to know whether adding nivolumab to standard chemotherapy (a medicine that kills cancer cells) could help to treat people with advanced or recurrent stomach or gastroesophageal junction cancer better than standard chemotherapy alone. They also wanted to know what side effects people taking the treatments had. People with advanced or recurrent stomach or gastroesophageal junction cancer who took part in the ATTRACTION-4 study were randomly divided into two groups. People in the first group were given intravenous infusion of nivolumab plus chemotherapy. People in the second group were given intravenous placebo plus chemotherapy. The doctors could choose between two standard chemotherapies, either oxaliplatin plus S-1 (also known as SOX) or oxaliplatin plus capecitabine (also known as CAPOX). Both options were standard of care for this type of cancer at the time of the study.
What are the key takeaways?
People receiving nivolumab plus chemotherapy lived longer without their cancer growing or spreading to other parts of the body (called progression-free survival) than people receiving placebo plus chemotherapy. The length of time people lived after starting the study treatments was similar in both groups, with median survival times of approximately 17 months. Many patients in the placebo plus chemotherapy group started nivolumab after their cancer had progressed. This may have helped to improve their overall survival. More people receiving nivolumab plus chemotherapy had their tumors shrink or disappear. The tumors continued to respond to treatment without growing or spreading for a longer time in people receiving nivolumab plus chemotherapy.
Adding nivolumab to standard chemotherapy did not result in any additional mental or physical health burden. During the study, some participants developed side effects related to the treatment. The three most common side effects were peripheral sensory neuropathy (a condition associated with impaired nerve function leading to numbness or pain in the hands or feet in particular), decreased appetite, and nausea (feeling sick) in both groups. The people receiving nivolumab plus chemotherapy had side effects that were similar to the known side effects of this treatment.
What do the results mean?
This study was designed to assess if the addition of nivolumab to standard chemotherapy might have a positive impact for Asian people with advanced or recurrent stomach or gastroesophageal junction cancer that did not have the HER2 protein. This is a type of cancer for which there are few treatments available. The study showed that nivolumab plus chemotherapy increase the length of time people with advanced or recurrent stomach cancer live without their cancer getting worse. Nivolumab plus chemotherapy has been approved as first-line treatment for advanced stomach cancer in more than 50 countries, including the United States, Japan, South Korea, and Taiwan.
Clinical trial number: NCT02746796
KEYWORDS: Gastric cancer, Nivolumab, Chemotherapy, First-line, Esophagogastric Junction
Acknowledgments
The sponsor and authors thank all of the patients who took part in the study, as well as the doctors and other staff for their invaluable roles in performing this study. We thank the Envision the Patient team, of Envision Pharma Group, for reviewing the use of patient-friendly language in this PLSP, and for organizing and providing feedback from a patient reviewer.
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Disclosure statement
Li-Tzong Chen reported support from Ono Pharmaceutical for an investigator-initiated study; honoraria for lectures from Ono Pharmaceutical, AstraZeneca, Astellas Pharma, and TTY Biopharm; is a member of a study steering committee for Ono Pharmaceutical; and has attended advisory board meetings for AstraZeneca, Astellas Pharma, TTY Biopharm, and MSD. Yoon-Koo Kang is a member of a scientific advisory board for HLB Pharma. Min-Hee Ryu reported grants or contracts from AstraZeneca; consulting fees from Bristol Myers Squibb, Ono Pharmaceutical, Novartis, Daiichi Sankyo, AstraZeneca, Eli Lilly, MSD, Astellas Pharma, Taiho Pharmaceutical, and Daehwa Pharmaceutical; and payments or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Bristol Myers Squibb, Ono Pharmaceutical, Novartis, Daiichi Sankyo, AstraZeneca, Eli Lilly, MSD, Astellas Pharma, and Daehwa Pharmaceutical. Do-Youn Oh reported grants or contracts from AstraZeneca, Novartis, Array, Eli Lilly, Servier, BeiGene, MSD, and Handok; and participation on a data safety monitoring board or advisory board for AstraZeneca, Novartis, Genentech/Roche, Merck Serono, Bayer, Taiho Pharmaceutical, ASLAN Pharmaceuticals, Halozyme, Zymeworks, Bristol Myers Squibb/ Celgene, BeiGene, Basilea, Turning Point Therapeutics, Yuhan, Arcus Biosciences, IQVIA, MSD, LG Chem, Astellas Pharma, AbbVie, J-Pharma, Mirati Therapeutics, Eutilex, Moderna, and Idience. Sun Young Rha reported grants or contracts for other studies from AstraZeneca, Ono Pharmaceutical, Eisai, Ipsen, Merck Sharp and Dohme, Merck KGaA, Pfizer, BeiGene, Astellas Pharma, Amgen, ALX Oncology, Zymeworks, Macrogenics, Seagen, Bold Therapeutics, MedPacto, ABL Bio, Daiichi Sankyo, Taiho Pharmaceutical, Leap Therapeutics, and Arcus Biosciences; consulting fees from LG Biochem and Indivumed; honoraria from MSD, Lilly, Daiichi Sankyo, Eisai, Ipsen, Amgen, Astellas Pharma, and Sanofi; and participation on a data safety monitoring board or advisory board for Amgen, Toray, and Arcus Biosciences. Keun-Wook Lee reported research grants for other studies from MSD, AstraZeneca, Merck KGaA, Roche, Pfizer, Amgen, Daiichi Sankyo, Astellas Pharma, BeiGene, GlaxoSmithKline, Taiho Pharmaceutical, Jazz Pharmaceuticals, ALX Oncology, Leap Therapeutics, TRIO, Exelixis, IgM Biosciences, Bolt Biotherapeutics, Trishula Therapeutics, InventisBio, Arcus Biosciences, Medicenna, Erasca, Macrogenics, Hanmi Pharmaceutical, MedPacto, Ildong Pharmaceutical, Elevar Therapeutics, Panolos Bioscience, Metafines, Genome & Company, Y-BIOLOGICS, and Wellmarker Bio; consulting fees from Astellas Pharma, Daiichi Sankyo, MSD, Ono Pharmaceutical, AbbVie, Guardant Health, Takeda Pharmaceutical, Metafines, and Pin Therapeutics; payments or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Astellas Pharma, Bayer, BeiGene, Daiichi Sankyo, Merck KGaA, and Sanofi/Aventis; and unpaid participation on a data safety monitoring board or advisory board for ALX Oncology. Takeshi Omori reported honoraria for lectures from Ono Pharmaceutical and Bristol Myers Squibb. Kohei Shitara reported research funding for other studies from Astellas Pharma, Ono Pharmaceutical, Daiichi Sankyo, Taiho Pharmaceutical, Chugai Pharmaceutical, MSD, Amgen, Eisai, PRA Health Sciences, Syneos Health, AstraZeneca, PPD-SNBL, and Toray; consulting fees for advisory roles from Bristol Myers Squibb, Takeda Pharmaceutical, Ono Pharmaceutical, Novartis, Daiichi Sankyo, Amgen, Boehringer Ingelheim, MSD, Astellas Pharma, Guardant Health Japan, Janssen Pharmaceutical, AstraZeneca, Zymeworks Biopharmaceuticals, ALX Oncology, Bayer, GlaxoSmithKline, HEALIOS, Moderna, and Arcus Biosciences; honoraria for lectures from Bristol Myers Squibb, Ono Pharmaceutical, Janssen Pharmaceutical, and AstraZeneca; and honoraria for educational activities from Eli Lilly and Astellas Pharma. Kensei Yamaguchi reported payments or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Daiichi Sankyo, Taiho Pharmaceutical, Chugai Pharmaceutical, Ono Pharmaceutical, Bristol Myers Squibb, Takeda Pharmaceutical, Eli Lilly Japan, and Merck Biopharma. Ken Kato reported consulting fees from Bristol Myers Squibb, Merck Sharp & Dohme, BeiGene, Roche, AstraZeneca, and Bayer; honoraria from Ono Pharmaceutical, Bristol Myers Squibb, and Taiho Pharmaceutical; and research funding for other studies from Ono Pharmaceutical, Bristol Myers Squibb, Merck Sharp & Dohme, BeiGene, Chugai Pharmaceutical, Shionogi, AstraZeneca, and Bayer. Shigenori Kadowaki reported grants or contracts from Ono Pharmaceutical, Taiho Pharmaceutical, MSD, Nobel Pharmaceutical, Janssen Pharmaceutical, Bayer, Eli Lilly, Chugai Pharmaceutical, Daiichi Sankyo, AbbVie, and AstraZeneca; and payments or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Ono Pharmaceutical, Taiho Pharmaceutical, MSD, Daiichi Sankyo, Merck KGaA, Bristol Myers Squibb, Eli Lilly, Chugai Pharmaceutical, Bayer, Eisai, and Novartis. Jen-Shi Chen reported consulting fees from Astellas Pharma, AstraZeneca, Daiichi Sankyo, MSD, and Bristol Myers Squibb; payments or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from MSD, TTY Biopharm, and Bristol Myers Squibb; and paid or unpaid leadership or fiduciary role in a board, society, committee or advocacy group from Astellas Pharma, Daiichi Sankyo, and MSD. Yasuhiro Choda reported honoraria for lectures from Bristol Myers Squibb. Hisateru Yasui reported honoraria for lectures from Ono Pharmaceutical, Chugai Pharmaceutical, Yakult Honsha, and Taiho Pharmaceutical. Kentaro Takeuchi, Yoshinori Hirashima, and Shunsuke Hagihara are employees of Ono Pharmaceutical. Narikazu Boku reported payments or honoraria from Bristol Myers Squibb, Ono Pharmaceutical, Taiho Pharmaceutical, Daiichi Sankyo, and Eli Lilly; and participation on a data safety monitoring board or advisory board for Kyowa Kirin. The other authors declared no conflicts of interest. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
Medical writing assistance was provided by Dr. Campbell Simpson of TrialWrite through EMC K.K., and was supported financially by Ono Pharmaceutical Co., Ltd.
Patient reviewers on this PLSP have received an honorarium from Future Oncology for their review work but have no other relevant financial relationships to disclose.
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.
Funding
The ATTRACTION-4 study was sponsored by Ono Pharmaceutical Co., Ltd. and Bristol Myers Squibb. Development of the original articles was funded by Ono Pharmaceutical Co., Ltd. and Bristol Myers Squibb. Ono Pharmaceutical Co., Ltd. funded the development and article processing fees for this plain language summary. The sponsors were involved in the collection, analysis, and interpretation of the data, as well as development and review of this plain language summary of a publication. The authors had full access to the data and took final responsibility for the decision to publish this summary.