Assessing Graded Histological Regression as Basis for Treatment Modification after Neoadjuvant Therapy in LAGC: An Exploratory Phase II Study.

In 30 seconds

This prospective, single-centre, open-label, randomised phase II trial assessed whether graded histologic regression (GHR) below 50% could guide adjuvant chemotherapy modification in locally advanced gastric cancer after neoadjuvant therapy. Fifty-eight patients with postoperative GHR < 50% received either a paclitaxel-modified or original regimen. At a median follow-up of 19.3 months, median disease-free survival was 25.2 months versus 11.4 months, respectively (HR 0.4711, 95% CI 0.2501-0.8874; P = 0.020); median overall survival was also longer with modification. The authors conclude that larger studies are needed to validate survival impact.

Key findings

• Median DFS was 25.2 months with the modified regimen versus 11.4 months with the original regimen (HR 0.4711, 95% CI 0.2501-0.8874; P = 0.020).
• Median OS was 32.0 months versus 18.0 months, respectively (HR 0.5088, 95% CI 0.2667-0.9708; P = 0.040).
• Patients with ypN3 stage showed greater OS benefit, while those with ypTNM III stage showed greater DFS benefit in subgroup analyses.
• Chemotherapy modification was not associated with significantly more adverse reactions overall, apart from a higher incidence of nausea.

Why it matters

The findings suggest that poor histologic regression after neoadjuvant therapy may help identify patients who could benefit from changing adjuvant chemotherapy. This is clinically relevant because the optimal response to ineffective neoadjuvant treatment remains uncertain. However, the results are exploratory and should be interpreted as evidence to test this response-guided strategy further, rather than as definitive proof of benefit.

What to keep in mind

This was a single-centre phase II trial with 58 patients and a median follow-up of 19.3 months; the authors state that a larger study is needed to validate survival impact.