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
Markus Moehler, Mikhail Dvorkin, Narikazu Boku, Mustafa Özgüroğlu, Min-Hee Ryu, Alina S Muntean, Sara Lonardi, Marina Nechaeva, Arinilda C Bragagnoli, Hasan S Coşkun, Antonio Cubillo Gracian, Toshimi Takano, Rachel Wong, Howard Safran, Gina M Vaccaro, Zev A Wainberg, Matthew R Silver, Huiling Xiong, Janet Hong, Julien Taieb, Yung-Jue Bang, Markus Moehler, Mikhail Dvorkin, Narikazu Boku, Mustafa Özgüroğlu, Min-Hee Ryu, Alina S Muntean, Sara Lonardi, Marina Nechaeva, Arinilda C Bragagnoli, Hasan S Coşkun, Antonio Cubillo Gracian, Toshimi Takano, Rachel Wong, Howard Safran, Gina M Vaccaro, Zev A Wainberg, Matthew R Silver, Huiling Xiong, Janet Hong, Julien Taieb, Yung-Jue Bang
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 [HR], 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.
Trial registration: ClinicalTrials.gov NCT02625610.
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References
- Leiting JL, Grotz TE: Advancements and challenges in treating advanced gastric cancer in the West. World J Gastrointest Oncol 11:652-664, 2019
- 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)
- 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
- National Comprehensive Cancer Network: NCCN clinical practice guidelines in oncology: Gastric cancer (version 4.2019). .
- 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
- 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
- Digklia A, Wagner AD: Advanced gastric cancer: Current treatment landscape and future perspectives. World J Gastroenterol 22:2403-2414, 2016
- Wagner AD Syn NL Moehler M, et al. : Chemotherapy for advanced gastric cancer. Cochrane Database Syst Rev 8:CD004064, 2017
- Alsina M Moehler M Hierro C, et al. : Immunotherapy for gastric cancer: A focus on immune checkpoints. Target Oncol 11:469-477, 2016
- 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
- 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
- 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
- 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)
- 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
- 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
- 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
- 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
- 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
- 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]
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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)
- 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.
- 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
Source: PubMed