3755 - A new docetaxel (DOC)-based triplet regimen does not improve the outcome of metastatic (M) or locally advanced (LA) gastric cancer (GC) as compared with an epirubicin (EPI) standard triplet regimen: a GISCAD trial.

Background

EOX (EPI + oxaliplatin-OHP + capecitabine-CAPE) is still one of the standard regimens for M or LA GC, but the role of EPI is today widely questioned and DOC replaced it in many institutions. A new DOC-based combination was developed with attempt at increasing efficacy/activity vs EOX without the heavy toxicity of the “classic” DOC regimen.

Methods

From 1/2013 to 11/2018, 169 previously untreated patients (pts) with M (87,6%) or LA GC were randomized by 23 centers between low-TOX (arm A) and EOX (arm B): Arm A: DOC: 35 mg/m2 iv, d 1 and 8 + OHP: 80 mg/m2 iv, d 1 + CAPE: 750 mg/ m2 x2 daily p.o. for 2 weeks Arm B: EPI: 50 mg/m2 iv, d 1 +OHP: 130 mg/m2 iv, d 1 +CAPE: 625 mg/m2 x2 daily p.o. for 3 weeks Both regimens recycled q 3 weeks If no PD or heavy toxicity, pts were programmed on therapy for a maximum of 5 (if CR) or 6 courses (if PR or SD). The primary endpoint was PFS, the secondary OS, ORR, DCR and tolerability. The study was designed to detect a 35% (80% power at a two side 5% significance level) PFS increase with low-TOX and an interim analysis for futility was planned after the first 127 events (75% of expected).

Results

At the cut-off date of interim analysis, 164 pts (median age 62 y; 63,9% male; ECOG PS: 0 in 75,7%) have available data for evaluation of primary efficacy analysis. The median PFS (KM) was 5.8 months (95% CI: 5.0 – 7.8) in arm A vs 6.5 months (95% CI: 5.0 – 8.9) in arm B, without statistical difference (NS). Also OS was comparable in the two arms: 12.2 (95% CI: 8.6 -16.0) vs 12.8 months (95% CI: 9.1-21.0). ORR were 22% and 35.4% and DCR 59.8% and 65.9%, respectively, again NS. The median number of courses per patient was 6 and treatment modification was higher in arm A (90,2% vs 78%) with a weakly higher number of AE with CTC ≥ 3 in arm A (54 vs 41).

Conclusions

These results indicate that, on the basis of the planned futility analysis, it is unlikely that low-TOX regimen is able to reach the target of improvement against EOX, both in efficacy/activity and in tolerability. Therefore, if the clinician’s choice is in favour of a triplet (i.e. in aggressive or very symptomatic disease), EOX could remain a standard option.

Clinical trial identification

NCT02076594.

Editorial acknowledgement

Legal entity responsible for the study

GISCAD.

Funding

Study carried out within the Rete Oncologica Lombarda-ROL project and founded as per the Deliberazioni di Giunta Regionale (DGR) di Regione Lombardia n° VIII/010761 dell’11-12-2009 e DGR IX/1485 del 30-03-2011”.

Disclosure

All authors have declared no conflicts of interest.