Cost-effectiveness of trifluridine/tipiracil against nivolumab for heavily pretreated metastatic gastric cancer in Japan.

OBJECTIVE: Nivolumab and trifluridine/tipiracil have significantly improved the overall survival of patients with heavily pretreated metastatic gastric cancer in different placebo-controlled phase III trials. Accordingly, nivolumab and trifluridine/tipiracil have been approved and recommended for patients with heavily pretreated metastatic gastric cancer in Japan. The aim of this study was to assess the cost-effectiveness of trifluridine/tipiracil against nivolumab. METHODS: A partitioned survival model, which consisted of three health states, namely, 'pre-progression,' 'post-progression,' and 'death,' was constructed. Efficacy and safety data were derived from the TAGS and ATTRACTION-2 trials. Costs were estimated based on the standard clinical pathway and national insurance fee schedules. One-way and probabilistic sensitivity analyses were performed. The threshold value was set to JPY 7 500 000 (USD 68 182) for each quality-adjusted life-year. RESULTS: The expected median overall survival and progression-free survival were 5.59 and 1.99 months for trifluridine/tipiracil and 5.26 and 1.55 months for nivolumab, respectively. The quality-adjusted life-year and expected costs per patient were 0.4379 and JPY 2 054 625 (USD 18 678) for trifluridine/tipiracil and 0.5295 and JPY 5 018 148 (USD 45 620) for nivolumab, respectively. The expected median progression-free survival and overall survival were equivalent with trifluridine/tipiracil and nivolumab, whereas the expected quality-adjusted life-year with trifluridine/tipiracil was slightly lower than that with nivolumab. However, trifluridine/tipiracil reduced the total treatment cost by JPY 2 963 523 (USD 26 996) compared with that of nivolumab. The incremental cost-effectiveness ratio of nivolumab versus trifluridine/tipiracil was JPY 32 352 489 (USD 294 113) per quality-adjusted life-year gained. CONCLUSIONS: Trifluridine/tipiracil was more cost-effective than nivolumab for patients with heavily pretreated metastatic gastric cancer.

Assessment of Pembrolizumab Therapy for the Treatment of Microsatellite Instability-High Gastric or Gastroesophageal Junction Cancer Among Patients in the KEYNOTE-059, KEYNOTE-061, and KEYNOTE-062 Clinical Trials.

IMPORTANCE: Immunotherapy has been associated with improved outcomes among patients who have received previous treatment for microsatellite instability-high (MSI-H) tumors. OBJECTIVE: To evaluate the antitumor activity of pembrolizumab therapy vs chemotherapy among patients with MSI-H advanced gastric or gastroesophageal junction (G/GEJ) cancer regardless of the line of therapy in which it was received. DESIGN, SETTING, AND PARTICIPANTS: This post hoc analysis of the phase 2 KEYNOTE-059 (third-line treatment or higher) single-arm trial and the phase 3 KEYNOTE-061 (second-line treatment) and KEYNOTE-062 (first-line treatment) randomized trials included patients with advanced G/GEJ cancer from 52 sites in 16 countries enrolled in KEYNOTE-059, 148 sites in 30 countries enrolled in KEYNOTE-061, and 200 sites in 29 countries enrolled in KEYNOTE-062. Patients were enrolled from March 2, 2015, to March 26, 2016, in KEYNOTE-059; from June 4, 2015, to July 26, 2016, in KEYNOTE-061; and from September 18, 2015, to May 26, 2017, in KEYNOTE-062, with data cutoff dates of August 8, 2018; October 26, 2017; and March 26, 2019; respectively. INTERVENTIONS: Pembrolizumab monotherapy in KEYNOTE-059, pembrolizumab monotherapy or chemotherapy (paclitaxel) in KEYNOTE-061, and pembrolizumab monotherapy, pembrolizumab plus chemotherapy (cisplatin and 5-fluorouracil or capecitabine), or chemotherapy alone in KEYNOTE-062. MAIN OUTCOMES AND MEASURES: Response was assessed centrally using Response Evaluation Criteria in Solid Tumours (RECIST), version 1.1; MSI-H status was determined centrally by polymerase chain reaction testing. RESULTS: At data cutoff, 7 of 174 patients (4.0%) in KEYNOTE-059, 27 of 514 patients (5.3%) in KEYNOTE-061, and 50 of 682 patients (7.3%) in KEYNOTE-062 had MSI-H tumors. Among those with MSI-H tumors, the median overall survival was not reached (NR) for pembrolizumab in KEYNOTE-059, KEYNOTE-061, and KEYNOTE-062 or for pembrolizumab plus chemotherapy in KEYNOTE-062. The median progression-free survival (PFS) for pembrolizumab was NR (95% CI, 1.1 months to NR) in KEYNOTE-059 and 17.8 months (95% CI, 2.7 months to NR) in KEYNOTE-061 (vs 3.5 months [95% CI, 2.0-9.8 months] for chemotherapy). In KEYNOTE-062, the median PFS was 11.2 months (95% CI, 1.5 months to NR) for pembrolizumab, NR (95% CI, 3.6 months to NR) for pembrolizumab plus chemotherapy, and 6.6 months (95% CI, 4.4-8.3 months) for chemotherapy. The objective response rate (ORR) for pembrolizumab was 57.1% in KEYNOTE-059 and 46.7% (vs 16.7% for chemotherapy) in KEYNOTE-061. In KEYNOTE-062, the ORR was 57.1% for pembrolizumab , 64.7% for pembrolizumab plus chemotherapy, and 36.8% for chemotherapy. CONCLUSIONS AND RELEVANCE: Findings from this study indicate that MSI-H status may be a biomarker for pembrolizumab therapy among patients with advanced G/GEJ cancer regardless of the line of therapy in which it was received. TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT02335411, NCT02370498, and NCT02494583.

Disease-free survival as a surrogate for overall survival in adjuvant trials of gastric cancer: a meta-analysis.

BACKGROUND: In investigations of the effectiveness of surgery and adjuvant chemotherapy for gastric cancers, overall survival (OS) is considered the gold standard endpoint. However, the disadvantage of using OS as the endpoint is that it requires an extended follow-up period. We sought to investigate whether disease-free survival (DFS) is a valid surrogate for OS in trials of adjuvant chemotherapy for gastric cancer. METHODS: The GASTRIC group initiated a meta-analysis of individual patient data collected in randomized clinical trials comparing adjuvant chemotherapy vs surgery alone for patients with curatively resected gastric cancer. Surrogacy of DFS was assessed through the correlation between the endpoints as well as through the correlation between the treatment effects on the endpoints. External validation of the prediction based on DFS was also evaluated. RESULTS: Individual patient data from 14 randomized clinical trials that included a total of 3288 patients were analyzed. The rank correlation coefficient between DFS and OS was 0.974 (95% confidence interval [CI] = 0.971 to 0.976). The coefficient of determination between the treatment effects on DFS and on OS was as high as 0.964 (95% CI = 0.926 to 1.000), and the surrogate threshold effect based on adjusted regression analysis was 0.92. In external validation, the six hazard ratios for OS predicted according to DFS were in very good agreement with those actually observed for OS. CONCLUSIONS: DFS is an acceptable surrogate for OS in trials of cytotoxic agents for gastric cancer in the adjuvant setting.