KEY TAKEAWAYS
- The VESTIGE phase II study (NCT03443856) aimed to evaluate the efficacy of adjuvant nivo/ipi compared to standard post-operative chemotherapy in high-risk resected GEA patients.
- The eligible patients were randomized 1:1 to receive either nivo/ipi or standard post-operative chemotherapy.
- The study concluded that nivo/ipi did not show improved DFS over chemotherapy in GEA patients with high recurrence risk following neoadjuvant chemotherapy and surgery.
Patients (pts) with Gastroesophageal adenocarcinoma (GEA) and tumor-positive lymph nodes (ypN+) or incomplete surgical resection (R1) who followed neoadjuvant chemo are at a high level of risk for relapse. The treatment is only effective for non-pathCR esophageal/GEJ pts after chemoradiotherapy and surgery and the activity of nivo/ipi in advanced GEA. The researchers hypothesized that nivo/ipi treatment would improve disease-free survival (DFS) compared to standard post-operative chemotherapy in these high-risk GEA patients.
In the study, eligible pts were randomly assigned 1:1 to receive standard post-operative adjuvant chemo (identical regimen as pre-operatively) or nivo 3mg/kg IV q2w plus ipilimumab (ipi) 1mg/kg IV q6w x 1 year. The primary endpoint was DFS, OS safety, toxicity, and quality of life. The study was structured to detect an increase in DFS rate from 5% to 74% (HR=0.7) at one year with nivo/ipi vs chemotherapy, one-sided alpha of 10%, using intent-to-treat analysis, and Cox regression to estimate treatment effect (hazard ratio, HR). The study data were reviewed from 191/240 patients, and EORTC IDMC was responsible for independently monitoring in June 2022. It recommended stopping the further enrollment of the pts.
At the time of this review, the median follow-up period was 11.1 months for 189 pts (94 chemo: 95 nivo/ipi). The median DFS for the chemo was 23.3m (95% CI 11.8- not reached (NR)) vs 11.9m (8.4–16.8m) for nivo/ipi HR 1.80 (95% CI 1.09– 2.98) p=0.02. The 12-month DFS rate is 62.2% and 49.3% for chemotherapy and nivo/ipi. The median OS was 25.1m (95% CI 18.6m – NR) HR 1.79 (95% CI 0.89 –3.59) p=0.1 and was not reached for the chemotherapy group. No new concerns regarding toxicity or early discontinuations were observed. The study concluded that the adjuvant treatment with nivolumab/ipilimumab did not show improved disease-free survival compared to chemotherapy in patients with GEA and a high risk for relapse after neoadjuvant chemotherapy and surgery. Subgroup and biomarker analyses are needed to identify potential beneficiaries of adjuvant immunotherapy, and EORTC IDMC recommends further analysis with longer follow-ups to validate these initial findings.
Source: https://www.annalsofoncology.org/article/S0923-7534(23)00163-1/fulltext
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT03443856
E. Smyth M. Mauer C. Cella I. Ben-Aharon G. Piessen L. Wyrwicz G. Al-Haidari T. Fleitas Kanonnikoff V. Boige M. Stahl U. Martens R. Obermannová C. Gomez-Martin P. Thuss-Patience V. Arrazubi A. Avallone K. Shiu M. Collienne A. Giraut F. Lordick Show less DOI:https://doi.org/10.1016/j.annonc.2023.04.021
