Pancreas

J Clin Oncol. 2024;42(9):1055–66

De La Fouchardière C, Malka D, Cropet C, Chabaud S, Raimbourg J, Botsen D, Launay S, Evesque L, Vienot A, Perrier H, Jary M, Rinaldi Y, Coutzac C, Bachet JB, Neuzillet C, Williet N, Desgrippes R, Grainville T, Aparicio T, Peytier A, Lecomte T, Roth GS, Thirot-Bidault A, Lachaux N, Bouché O, Ghiringhelli F

Gemcitabine and paclitaxel versus gemcitabine alone after 5-fluorouracil, oxaliplatin, and irinotecan in metastatic pancreatic adenocarcinoma: A randomized phase 3 PRODIGE 65-UCGI 36-GEMPAX UNICANCER study

Purpose: GEMPAX was an open-label, randomized phase 3 clinical trial designed to assess the efficacy and tolerability of gemcitabine plus paclitaxel versus gemcitabine alone as second-line treatment for patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) who previously received 5-fluorouracil, oxaliplatin, and irinotecan (FOLFIRINOX).
Methods: Patients with histologically or cytologically confirmed mPDAC were randomly assigned (2:1) to receive GEMPAX (paclitaxel 80 mg/m² + gemcitabine 1000 mg/m²; i.v.; once at day (D)1, D8, and D15/arm A) or gemcitabine alone (arm B) once at D1, D8, and D15 every 28 days until progression, toxicity, or patient’s decision. The primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), objective response rate (ORR), quality of life, and safety.
Results: Overall, 211 patients (median age, 64 [30–86] years; 62% male) were included. After a median study follow-up for alive patients of 13.4 versus 13.8 months in arm A versus arm B, the median OS (95% confidence interval) was 6.4 (5.2–7.4) versus 5.9 months (4.6–6.9; hazard ratio [HR] = 0.87 [0.63–1.20]; p = 0.4095), the median PFS was 3.1 (2.2–4.3) versus 2.0 months (1.9–2.3; HR = 0.64 [0.47–0.89]; p = 0.0067), and the ORR was 17.1% (11.3–24.4) versus 4.2% (0.9–11.9; p = 0.008) in arm A versus arm B, respectively. Overall, 16.7% of patients in arm A and 2.9% in arm B discontinued their treatment because of adverse events (AEs). One grade 5 AE associated with both gemcitabine and paclitaxel was reported in arm A (acute respiratory distress), and 58.0% versus 27.1% of patients experienced grade ≥ 3 treatment-related AEs in arm A versus arm B, among which 15.2% versus 4.3% had anemia, 15.9% versus 15.7% had neutropenia, 19.6% versus 4.3% had thrombocytopenia, 10.1% versus 2.9% had asthenia and 12.3% versus 0.0% had neuropathy.

Conclusion: While gemcitabine plus paclitaxel did not meet the primary end point of overall survival versus gemcitabine alone in patients with metastatic pancreatic ductal adenocarcinoma in the second-line setting, both progression-free survival and objective response rate were significantly improved.

DOI: 10.1200/jco.23.00795