1528P - TCOG T5221 trial: A phase II randomized study of gemcitabine and nab-paclitaxel in combination with S- 1/LV (GASL) or oxaliplatin (GAP) as first-line treatment for metastatic pancreatic cancer

Background

Gemcitabine plus nab-paclitaxel (GnP), given weekly for consecutive 3 weeks every 4 weeks, is one of the standard treatment for metastatic pancreatic adenocarcinoma (mPDAC); however, the objective response rate (ORR) is only 23% and the standard GnP is too toxic for Asian (71% grade 3–4 neutropenia in the Japanese study). Prior study showed biweekly GnP could reduce toxicities, which provided the opportunity to add other agents to overcome tumor heterogeneity. This study aims to assess the efficacy and safety of biweekly GnP plus either S-1/LV (GASL) or oxaliplatin (GAP).

Methods

The major inclusion criteria were histologically confirmed mPDAC with adequate organ functions. The primary endpoint was ORR. Utilizing a 'pick the winner' approach, a parallel Simon two-stage design was employed to test if ORR could achieve 41% in either arm. The study arm would proceed to the second stage if there were 6 or more responders among the first 24 patients in each arm. Both arm consisted of nab-paclitaxel 125 mg/m², gemcitabine 800 mg/m² on day 1 in a 2-week cycle while GASL arm adding oral S-1 60-100 mg per day and leucovorin 30 mg BID on day 1-7 and GAP adding oxaliplatin 75 mg/m² on day 1.

Results

Between January and December 2022, the initial 50 patients were randomly assigned to GASL (n=27) and GAP (n=23). At the interim analysis, due to futility, GAP arm was closed in the first stage. Subsequently, all patients were assigned to the GASL arm to a final number of 43. The GASL arm met its primary endpoint, with an ORR of 53.5%, while the ORR of the GAP arm was 17.4%. The median duration of follow-up was 17.7 months (95% CI, 12.0-18.0). The median progression-free survival was 8.6 months (95% CI, 7.4-not reached) in the GASL arm and 5.4 months (95% CI, 3.0-9.0) in the GAP arm. The corresponding median overall survival was 14.6 months (95% CI, 7.0 – not reached) and 7.7 months (95% CI, 5.6-11.7). The most common grade 3-4 adverse events were neutropenia and anemia (up to 14%) in both arm.

Conclusions

GASL demonstrated high ORR with promising survival and relatively low toxicity and could be considered as an alternative first-line regimen in Asian mPDAC.

Clinical trial identification

NCT05026905.

Editorial acknowledgement

Legal entity responsible for the study

L-T. Chen.

Funding

National Health Research Institutes.

Disclosure

All authors have declared no conflicts of interest.