Data Support Further Research for Neoadjuvant Chemo Plus CRT in Resectable Gastric Adenocarcinoma

Treatment with chemoradiotherapy (CRT) alone or in combination with preoperative chemotherapy met the efficacy threshold for event-free survival (EFS) in patients with resectable gastric cancer, whereas chemotherapy alone did not reach the EFS benchmark, according to data from the phase 2 CRITICS-II trial presented at the 2026 Gastrointestinal Cancers Symposium.¹

In this 3-arm study, a 1-year EFS rate of 60% or below was deemed unsuccessful, and a rate of 75% or higher was considered effective enough.

At 1 year, the EFS rate was 68% (95% CI, 58%-80%) in arm 1, which included patients who received chemotherapy alone. Additionally, the 1-year EFS rates were 84% (95% CI, 75%-84%) for patients who received chemotherapy plus CRT in arm 2 and 78% (95% CI, 69%-88%) for those who received CRT alone in arm 3. In arms 1, 2, and 3, the 1-year overall survival (OS) rates were 74% (95% CI, 64%-85%), 89% (95% CI, 81%-97%), and 84% (95% CI, 76%-93%), respectively.

Additional data showed that in arms 1, 2, and 3, respectively, the rates of preoperative compliance were 81%, 65%, and 84%; the rates grade 3 to 5 preoperative toxicities were 56%, 55%, and 43%. Additionally, surgery-related complications occurred in 21%, 15%, and 21% of patients in each group, and the rates of pathological complete response (pCR) were 8%, 20%, and 13%.

“If we look at the different end points together, we concluded, first, that arm 1…did not fulfill the threshold of 75% for EFS at 1 year. If we take into account the survival results, surgical complications, and [pCRs], ‘total neoadjuvant’ chemotherapy plus [CRT] was identified as the preferred preoperative regimen,” lead study author Marcel Verheij, MD, PhD, from the Department of Radiation Oncology at Radboud University Medical Center, stated in his presentation of the data.

Investigators of the CRITICS-II trial aimed to identify an optimal preoperative regimen for patients with resectable gastric cancer while omitting adjuvant therapy by comparing 3 investigational strategies. In arm 1, 68 patients were assigned to receive adjuvant chemotherapy alone for 4 cycles every 3 weeks, which consisted of docetaxel at 50 mg/m² on day 1, oxaliplatin at 100 mg/m² on day 1, and capecitabine at 850 mg/m² m every 2 days on days 1 to 14. In arm 2, 65 patients received chemotherapy followed by CRT consisting of 45 Gy in 25 fractions plus concurrent paclitaxel at 50 mg/m² and carboplatin area under the curve 2 on days 1, 8, 15, 22, and 29 of each cycle. In arm 3, 68 patients received CRT alone. All patients underwent total or subtotal gastrectomy plus extended lymphadenectomy, with a removal of at least 15 lymph nodes.

The trial’s primary end point was EFS at 1 year. Secondary end points included patient compliance, time to event, OS, pCR, the R0 resection rate, complications or toxicities, and health-related quality of life.

Patients 18 years and older with stage IB to IIIC gastric cancer, resectable adenocarcinoma of the stomach or gastroesophageal junction (GEJ), and a WHO performance status of less than 2 were eligible for enrollment on the trial.² Having negative staging laparoscopy and no distant metastases were additional requirements for study entry.

Across the overall population, 63% of patients were male, and the median age was 67 years (range, 38-82). Of note, 12%, 16% and 4% of patients in arms 1, 2, and 3, respectively, had GEJ-based tumors. Overall, 79%, 63%, and 78% of patients from each arm completed all stages of treatment in the study.

Adverse effects (AEs) of grade 0 to 2 occurred in 49% of all patients, and grade 3/4 events occurred in 49%. There were 4 grade 5 AEs, which included gastrointestinal events (n = 2) and infectious toxicity (n = 1) in arm 1 and respiratory toxicity (n = 1) in arm 2. Of note, 57% of patients in arm 3 had grade 0 to 2 AEs, while 43% experienced grade 3/4 events; none had grade 5 toxicity.

In arms 1, 2, and 3, respectively, the most common type of gastrectomy was a total resection (48% vs 48% vs 46%). Additionally, the most common type of lymphadenectomy in each group was D2 procedure (74% vs 66% vs 65%).

Regarding pathological results, Verheij noted that 55%, 59%, and 57% of patients in arms 1, 2, and 3, respectively, had pN0 disease. Furthermore, an R0 resection occurred in 98%, 91%, and 93% of each respective arm. The median number lymph nodes resected was 31 (range, 14-83) in arm 1, 23 (range, 0-42) in arm 2, and 21 (range, 8-47) in arm 3.

References

1. Verheij M, van Grieken NCT, Slagter AE, et al. CRITICS-II: A multicenter randomized phase II trial of neo-adjuvant chemotherapy followed by surgery versus neo-adjuvant chemotherapy and subsequent chemoradiotherapy followed by surgery versus neo-adjuvant chemoradiotherapy followed by surgery in resectable gastric cancer. J Clin Oncol. 2026;44(suppl 2):283. doi:10.1200/JCO.2026.44.2_suppl.283
2. Multicentric randomised trial for resectable gastric cancer (CRITICS-II). ClinicalTrials.gov. Updated May 2, 2024. Accessed January 8, 2026. https://tinyurl.com/bdfnc6v5