15 januari 2024:
zie ook dit artikel: https://kanker-actueel.nl/maagkanker-onderhoudstherapie-met-immuuntherapie-met-avelumab-na-chemotherapie-geeft-verbeterde-2-jaars-overleving-van-6-maanden-in-vergelijking-met-voortzetting-van-chemotherapie.html
9 januari 2024: Zie ook dit artikel: https://kanker-actueel.nl/immuuntherapie-vooraf-aan-operatie-en-chemotherapie-blijkt-succesvol-bij-kankerpatienten-met-maagkanker-en-met-tumoren-op-de-overgang-van-slokdarm-naar-de-maag.html
2 december 2017: Klik op de titel
the phase III JAVELIN Gastric 300 trial did not meet its primary endpoint of superior overall survival with single-agent avelumab (Bavencio) compared with physician's choice of chemotherapy.
The trial investigated avelumab as a third-line treatment for unresectable, recurrent, or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma patients whose disease progressed following two prior therapeutic regimens, regardless of programmed cell death ligand 1 (PD-L1) expression. The safety profile of avelumab was consistent with that observed in the overall JAVELIN clinical development program.
Abstract
Purpose
The role of maintenance therapy for gastric (GC) or gastroesophageal junction cancer (GEJC) is unclear. We investigated avelumab (anti–programmed death ligand-1 [PD-L1]) maintenance after first-line induction chemotherapy for GC/GEJC.
Patients and Methods
JAVELIN Gastric 100 was a global, open-label, phase III trial. Eligible patients had untreated, unresectable, human epidermal growth factor receptor 2–negative, locally advanced or metastatic GC or GEJC. Patients without progressive disease after 12 weeks of first-line chemotherapy with oxaliplatin plus a fluoropyrimidine were randomly assigned 1:1 to avelumab 10 mg/kg every 2 weeks or continued chemotherapy, stratified by region (Asia v non-Asia). The primary end point was overall survival (OS) after induction chemotherapy in all randomly assigned patients or the PD-L1–positive randomly assigned population (≥ 1% of tumor cells; 73-10 assay).
Results
A total of 805 patients received induction; 499 were randomly assigned to avelumab (n = 249) or continued chemotherapy (n = 250). Median OS was 10.4 months (95% CI, 9.1 to 12.0 months) versus 10.9 months (95% CI, 9.6 to 12.4 months) and 24-month OS rate was 22.1% versus 15.5% with avelumab versus chemotherapy, respectively (hazard ratio , 0.91; 95% CI, 0.74 to 1.11; P = .1779). In the PD-L1–positive population (n = 54), the HR for OS was 1.13 (95% CI, 0.57 to 2.23; P = .6352). In an exploratory analysis of the PD-L1–positive population, defined as combined positive score ≥ 1 (22C3 assay; n = 137), median OS was 14.9 months (95% CI, 8.7 to 17.3 months) with avelumab versus 11.6 months (95% CI, 8.4 to 12.6 months) with chemotherapy (unstratified HR, 0.72; 95% CI, 0.49 to 1.05). With avelumab and chemotherapy, treatment-related adverse events (TRAEs) occurred in 149 (61.3%) and 184 (77.3%) patients, including grade ≥ 3 TRAEs in 31 (12.8%) and 78 (32.8%) patients, respectively.
Conclusion
JAVELIN Gastric 100 did not demonstrate superior OS with avelumab maintenance versus continued chemotherapy in patients with advanced GC or GEJC overall or in a prespecified PD-L1–positive population.
Acknowledgment
We thank Ilaria Conti, Sara Georges, Mary Ruisi, and Silke Scheller of Merck KGaA, Darmstadt, Germany for their contributions to the study as well as the patients and their families and the investigators, coinvestigators, and study teams at each of the participating centers. Medical writing assistance was provided by Mark Holland of ClinicalThinking and funded by Merck KGaA, Darmstadt, Germany and Pfizer.
Study Protocol
The following protocol information is provided solely to describe how the authors conducted the research underlying this article. The information provided may not reflect the complete protocol or any previous amendments or modifications. As described in the Journal Policies, JCO requests only specific elements of the most recent version of the protocol. The protocol information is not intended to replace good clinical judgment in selecting appropriate therapy and in determining drug doses, schedules, and dose modifications. The treating physician or other health care provider is responsible for determining the best treatment for the patient. ASCO and JCO assume no responsibility for any injury or damage to persons or property arising out of the use of this protocol material or due to any errors or omissions. Readers seeking additional information about the protocol are encouraged to consult the corresponding author directly.
Please click the protocol link below to access the information.
Prior Presentation
Presented in part at the American Society of Clinical Oncology Gastrointestinal Cancers Symposium, San Francisco, CA, January 23-25, 2020
Support
Supported by Merck KGaA, Darmstadt, Germany, as part of an alliance between Merck KGaA and Pfizer.
Clinical Trial Information
NCT02625610 (JAVELIN Gastric 100)
Authors' Disclosures of Potential Conflicts of Interest
Phase III Trial of Avelumab Maintenance After First-Line Induction Chemotherapy Versus Continuation of Chemotherapy in Patients With Gastric Cancers: Results From JAVELIN Gastric 100
The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center.
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Markus Moehler
Honoraria: Taiho Pharmaceutical, Eli Lilly/ImClone, Amgen, Roche/Genentech, Merck KGaA, Darmstadt, Germany, MSD Oncology, Bristol Myers Squibb, AstraZeneca/MedImmune, Servier
Consulting or Advisory Role: Bayer, Merck Sharp & Dohme, Merck KGaA, Darmstadt, Germany, Amgen, Taiho Pharmaceutical, Nordic Group, Pfizer, Yakult, Roche, Eli Lilly, Servier
Research Funding: Amgen (Inst), Leap Therapeutics (Inst), Merck KGaA, Darmstadt, Germany (Inst), Jennerex (Inst), AstraZeneca (Inst), Merck Sharp & Dohme (Inst)
Travel, Accommodations, Expenses: Amgen, Merck KGaA, Darmstadt, Germany, Roche, Bayer, American Society of Clinical Oncology, German Cancer Society, Merck Sharp & Dohme, European Society for Medical Oncology
Narikazu Boku
Honoraria: Taiho Pharmaceutical, Ono Pharmaceutical, Bristol Myers Squibb Japan
Research Funding: Bristol Myers Squibb (Inst), Ono Pharmaceutical (Inst), Taiho Pharmaceutical (Inst), Takeda (Inst)
Mustafa Özgüroğlu
Honoraria: Astellas Pharma, Novartis, Janssen Oncology (Inst)
Consulting or Advisory Role: MSD Oncology, AstraZeneca
Speakers’ Bureau: AstraZeneca
Travel, Accommodations, Expenses: AstraZeneca
Min-Hee Ryu
Honoraria: Dae Hwa Pharmaceutical, Bristol Myers Squibb, Eli Lilly, Ono Pharmaceutical, Merck Sharp & Dohme, Taiho Pharmaceutical, Novartis
Consulting or Advisory Role: Dae Hwa Pharmaceutical, Bristol Myers Squibb, Eli Lilly, Ono Pharmaceutical, Merck Sharp & Dohme, Taiho Pharmaceutical, Novartis
Sara Lonardi
Consulting or Advisory Role: Amgen, Merck KGaA, Darmstadt, Germany, Eli Lilly, Servier
Speakers’ Bureau: Roche, Eli Lilly, Bristol Myers Squibb, Servier, Merck Serono
Research Funding: Amgen, Merck KGaA, Darmstadt, Germany
Hasan S. Coşkun
Consulting or Advisory Role: Nestle Health Science
Speakers’ Bureau: Eli Lilly, Astellas Pharma
Travel, Accommodations, Expenses: Pfizer, Amgen, Bristol Myers Squibb
Toshimi Takano
Honoraria: Daiichi Sankyo, Eisai, Pfizer, Eli Lilly, Chugai Pharma, Kyowa Hakko Kirin, Celltrion Healthcare
Research Funding: Taiho Pharmaceutical (Inst), Novartis (Inst), Ono Pharmaceutical (Inst), Merck Sharp & Dohme (Inst), Merck KGaA, Darmstadt, Germany (Inst), Daiichi Sankyo (Inst), Eisai (Inst), Bristol Myers Squibb (Inst), Chugai Pharma (Inst), Kyowa Hakko Kirin (Inst)
Gina M. Vaccaro
Consulting or Advisory Role: Bayer, Exelixis, Taiho Pharmaceutical, AstraZeneca, Incyte, Amgen, Novartis, Celgene, Astellas Pharma, QED Therapeutics
Research Funding: Celgene, Merck Sharp & Dohme, Eli Lilly, Astellas Pharma, EMD Serono, Inc (an affiliate of Merck KGaA, Darmstadt, German), Incyte, Bristol Myers Squibb, Array BioPharma, Newlink Genetics, Polaris, Boston Scientific
Zev A. Wainberg
Consulting or Advisory Role: Array BioPharma, Five Prime Therapeutics, Novartis, Eli Lilly, Merck & Co, Merck KGaA, Darmstadt, Germany, Bristol Myers Squibb, Bayer, AstraZeneca/MedImmune, Ipsen, Macrogenics
Research Funding: Novartis (Inst), Plexxikon (Inst), Pfizer (Inst), Merck & Co (Inst), Five Prime Therapeutics (Inst)
Travel, Accommodations, Expenses: Eli Lilly, Merck & Co, Bayer
Matthew R. Silver
Employment: EMD Serono Research & Development Institute, Inc (an affiliate of Merck KGaA, Darmstadt, Germany)
Huiling Xiong
Employment: EMD Serono Research & Development Institute, Inc (an affiliate of Merck KGaA, Darmstadt, Germany)
Janet Hong
Employment: EMD Serono Research & Development Institute, Inc (an affiliate of Merck KGaA, Darmstadt, Germany), Alnylam (I)
Stock and Other Ownership Interests: EMD Serono, Alnylam (I), Bristol Myers Squibb, Sanofi
Julien Taieb
Consulting or Advisory Role: Roche, Merck KGaA, Darmstadt, Germany, Amgen, Celgene, Eli Lilly, Servier, Sirtex Medical, Merck Sharp & Dohme, Pierre Fabre
Speakers’ Bureau: Servier, Amgen, Roche/Genentech, Sanofi, Merck KGaA, Darmstadt, Germany, Eli Lilly, Merck Sharp & Dohme, Pierre Fabre
Yung-Jue Bang
Consulting or Advisory Role: Samyang, BeiGene, Green Cross, Taiho Pharmaceutical, Merck KGaA, Darmstadt, Germany, AstraZeneca/MedImmune, Novartis, MSD Oncology, Bayer, Hanmi, Genentech/Roche, Eli Lilly, Daiichi Sankyo, Astellas Pharma, Bristol Myers Squibb, Genexine, GlaxoSmithKline
Research Funding: AstraZeneca/MedImmune (Inst), Novartis (Inst), Genentech/Roche (Inst), Merck Sharp & Dohme (Inst), Merck KGaA, Darmstadt, Germany (Inst), Bayer (Inst), GlaxoSmithKline (Inst), Bristol Myers Squibb (Inst), Pfizer (Inst), Eli Lilly (Inst), Boehringer Ingelheim (Inst), Macrogenics (Inst), Boston Biomedical (Inst), Five Prime Therapeutics (Inst), CKD (Inst), Ono Pharmaceutical (Inst), Taiho Pharmaceutical (Inst), Takeda (Inst), BeiGene (Inst), Curis (Inst), Green Cross (Inst), Daiichi Sankyo (Inst), Astellas Pharma (Inst), Genexine (Inst)
No other potential conflicts of interest were reported.
References
1.
Leiting JL, Grotz TE: Advancements and challenges in treating advanced gastric cancer in the West. World J Gastrointest Oncol 11:652-664, 2019
2.
Smyth EC, Verheij M, Allum W, et al: Gastric cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 27:v38-v49, 2016 (suppl 5)
3.
Muro K, Lordick F, Tsushima T, et al: Pan-Asian adapted ESMO clinical practice guidelines for the management of patients with metastatic oesophageal cancer: A JSMO-ESMO initiative endorsed by CSCO, KSMO, MOS, SSO and TOS. Ann Oncol 30:34-43, 2019
4.
National Comprehensive Cancer Network: NCCN clinical practice guidelines in oncology: Gastric cancer (version 4.2019). https://www.nccn.org/professionals/physician_gls/pdf/gastric.pdf
5.
Koizumi W, Narahara H, Hara T, et al: S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced gastric cancer (SPIRITS trial): A phase III trial. Lancet Oncol 9:215-221, 2008
6.
Lordick F, Kang YK, Chung HC, et al: Capecitabine and cisplatin with or without cetuximab for patients with previously untreated advanced gastric cancer (EXPAND): A randomised, open-label phase 3 trial. Lancet Oncol 14:490-499, 2013
7.
Digklia A, Wagner AD: Advanced gastric cancer: Current treatment landscape and future perspectives. World J Gastroenterol 22:2403-2414, 2016
8.
Wagner AD, Syn NL, Moehler M, et al: Chemotherapy for advanced gastric cancer. Cochrane Database Syst Rev 8:CD004064, 2017
9.
Alsina M, Moehler M, Hierro C, et al: Immunotherapy for gastric cancer: A focus on immune checkpoints. Target Oncol 11:469-477, 2016
10.
Ciuleanu T, Brodowicz T, Zielinski C, et al: Maintenance pemetrexed plus best supportive care versus placebo plus best supportive care for non-small-cell lung cancer: A randomised, double-blind, phase 3 study. Lancet 374:1432-1440, 2009
11.
Coleman RL, Oza AM, Lorusso D, et al: Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): A randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 390:1949-1961, 2017
12.
Mirza MR, Monk BJ, Herrstedt J, et al: Niraparib maintenance therapy in platinum-sensitive, recurrent ovarian cancer. N Engl J Med 375:2154-2164, 2016
13.
Poveda A, Floquet A, Ledermann JA, et al: Final overall survival (OS) results from SOLO2/ENGOT-ov21: A phase III trial assessing maintenance olaparib in patients (pts) with platinum-sensitive, relapsed ovarian cancer and a BRCA mutation. J Clin Oncol 38, 2020 (suppl; abstr 6002)
14.
Bang YJ, Cho JY, Kim YH, et al: Efficacy of sequential ipilimumab monotherapy versus best supportive care for unresectable locally advanced/metastatic gastric or gastroesophageal junction cancer. Clin Cancer Res 23:5671-5678, 2017
15.
Meulendijks D, de Groot JW, Los M, et al: Bevacizumab combined with docetaxel, oxaliplatin, and capecitabine, followed by maintenance with capecitabine and bevacizumab, as first-line treatment of patients with advanced HER2-negative gastric cancer: A multicenter phase 2 study. Cancer 122:1434-1443, 2016
16.
Eren OO, Ozturk MA, Sonmez OU, et al: Safety, feasibility, and efficacy of capecitabine maintenance in patients with advanced gastric cancer: A retrospective study. Am J Ther 23:e1493-e1497, 2016
17.
Kang YK, Boku N, Satoh T, et al: Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2): A randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 390:2461-2471, 2017
18.
Bang YJ, Kang YK, Catenacci DV, et al: Pembrolizumab alone or in combination with chemotherapy as first-line therapy for patients with advanced gastric or gastroesophageal junction adenocarcinoma: Results from the phase II nonrandomized KEYNOTE-059 study. Gastric Cancer 22:828-837, 2019
19.
Fuchs CS, Doi T, Jang RW, et al: Safety and efficacy of pembrolizumab monotherapy in patients with previously treated advanced gastric and gastroesophageal junction cancer: Phase 2 clinical KEYNOTE-059 trial. JAMA Oncol 4:e180013, 2018 [Erratum: JAMA Oncol 5:579, 2019]
20.
Muro K, Chung HC, Shankaran V, et al: Pembrolizumab for patients with PD-L1-positive advanced gastric cancer (KEYNOTE-012): A multicentre, open-label, phase 1b trial. Lancet Oncol 17:717-726, 2016
21.
Shitara K, Özgüroğlu M, Bang YJ, et al: Pembrolizumab versus paclitaxel for previously treated, advanced gastric or gastro-oesophageal junction cancer (KEYNOTE-061): A randomised, open-label, controlled, phase 3 trial. Lancet 392:123-133, 2018
22.
Gulley JL, Rajan A, Spigel DR, et al: Avelumab for patients with previously treated metastatic or recurrent non-small-cell lung cancer (JAVELIN Solid Tumor): Dose-expansion cohort of a multicentre, open-label, phase 1b trial. Lancet Oncol 18:599-610, 2017
23.
Disis ML, Taylor MH, Kelly K, et al: Efficacy and safety of avelumab for patients with recurrent or refractory ovarian cancer: Phase 1b results from the JAVELIN Solid Tumor trial. JAMA Oncol 5:393-401, 2019
24.
Patel MR, Ellerton J, Infante JR, et al: Avelumab in metastatic urothelial carcinoma after platinum failure (JAVELIN Solid Tumor): Pooled results from two expansion cohorts of an open-label, phase 1 trial. Lancet Oncol 19:51-64, 2018
25.
Le Tourneau C, Hoimes C, Zarwan C, et al: Avelumab in patients with previously treated metastatic adrenocortical carcinoma: Phase 1b results from the JAVELIN Solid Tumor trial. J Immunother Cancer 6:111, 2018
26.
Keilholz U, Mehnert JM, Bauer S, et al: Avelumab in patients with previously treated metastatic melanoma: Phase 1b results from the JAVELIN Solid Tumor trial. J Immunother Cancer 7:12, 2019
27.
Hassan R, Thomas A, Nemunaitis JJ, et al: Efficacy and safety of avelumab treatment in patients with advanced unresectable mesothelioma: Phase 1b results from the JAVELIN Solid Tumor trial. JAMA Oncol 5:351-357, 2019
28.
Chung HC, Arkenau HT, Lee J, et al: Avelumab (anti-PD-L1) as first-line switch-maintenance or second-line therapy in patients with advanced gastric or gastroesophageal junction cancer: Phase 1b results from the JAVELIN Solid Tumor trial. J Immunother Cancer 7:30, 2019
29.
Kulangara K, Zhang N, Corigliano E, et al: Clinical utility of the combined positive score for programmed death ligand-1 expression and the approval of pembrolizumab for treatment of gastric cancer. Arch Pathol Lab Med 143:330-337, 2019
30.
Hassan R, Thomas A, Nemunaitis JJ, et al: Avelumab in patients with previously treated mesothelioma: Updated phase 1b results from the JAVELIN Solid Tumor trial. J Clin Oncol 36, 2018 (suppl; abstr 166)
31.
Shitara K, Van Cutsem E, Bang YJ, et al. Efficacy and safety of pembrolizumab or pembrolizumab plus chemotherapy vs chemotherapy alone for patients with first-line, advanced gastric cancer: The KEYNOTE-062 Phase 3 randomized clinical trial. JAMA Oncol 6:1-10, 2020
32.
Bang YJ, Ruiz EY, Van Cutsem E, et al: Phase III, randomised trial of avelumab versus physician’s choice of chemotherapy as third-line treatment of patients with advanced gastric or gastro-oesophageal junction cancer: Primary analysis of JAVELIN Gastric 300. Ann Oncol 29:2052-2060, 2018
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