Memorial Sloan Kettering Cancer Center, New York, NY
Eileen Mary O'Reilly , Davide Melisi , Teresa Macarulla , Roberto A. Pazo Cid , Sreenivasa R Chandana , Christelle De La Fouchardiere , Andrew Peter Dean , Igor Kiss , Woo Jin Lee , Thorsten Oliver Goetze , Eric Van Cutsem , Scott Paulson , Tanios S. Bekaii-Saab , Shubham Pant , Richard Hubner , Zhimin Xiao , Huanyu Chen , Fawzi Benzaghou , Zev A. Wainberg
Background: Liposomal irinotecan + 5-fluorouracil/leucovorin (5-FU/LV) is approved in the USA and Europe for mPDAC following progression with gemcitabine-based therapy. A phase 1/2 study (NCT02551991) demonstrated promising anti-tumor activity in patients with mPDAC who received first-line liposomal irinotecan 50 mg/m2 + 5-FU 2400 mg/m2 + LV 400 mg/m2 + oxaliplatin 60 mg/m2 (NALIRIFOX). Here, we present results from NAPOLI 3 (NCT04083235), a randomized, open-label, phase 3 study investigating the efficacy and safety of NALIRIFOX compared with nab-paclitaxel 125 mg/m2 + gemcitabine 1000 mg/m2 (Gem+NabP) as first-line therapy in patients with mPDAC. Methods: Eligible patients with histopathologically/cytologically confirmed untreated mPDAC were randomized (1:1; stratified by Eastern Cooperative Oncology Group [ECOG] performance status, geographic region and presence/absence of liver metastases) to receive NALIRIFOX on days 1 and 15 of a 28-day cycle or Gem+NabP on days 1, 8 and 15 of a 28-day cycle. The primary endpoint was overall survival (OS); secondary endpoints were progression-free survival (PFS), overall response rate (ORR) and safety. OS was evaluated when at least 543 events were observed using a stratified log-rank test with an overall one-sided significance level of 0.025. Results: Overall, 770 patients (NALIRIFOX, n = 383; Gem+NabP, n = 387) were included. Baseline characteristics were balanced between arms. At a median follow-up of 16.1 months, 544 events had occurred. Median OS was 11.1 months in the NALIRIFOX group versus 9.2 months in the Gem+NabP group; median PFS was 7.4 months versus 5.6 months. Median (95% CI) duration of response was 7.3 (5.8–7.6) and 5.0 (3.8–5.6) months in patients who received NALIRIFOX and Gem+NabP, respectively. Grade 3/4 treatment-emergent adverse events occurring in at least 10% of patients receiving NALIRIFOX versus Gem+NabP included diarrhea (20.3% vs 4.5%), nausea (11.9% vs 2.6%), hypokalemia (15.1% vs 4.0%), anemia (10.5% vs 17.4%) and neutropenia (14.1% vs 24.5%). Conclusions: First-line NALIRIFOX demonstrated clinically meaningful and statistically significant improvement in OS and PFS compared with Gem+NabP in patients with mPDAC. The NALIRIFOX safety profile was consistent with the profiles of the regimen components and generally manageable. Clinical trial information: NCT04083235.
NALIRIFOX (n = 383) | Gem+NabP (n = 387) | |||
---|---|---|---|---|
OS, months, median (95% CI) | 11.1 (10.0–12.1) | 9.2 (8.3–10.6) | ||
HR (95% CI); p value | 0.83 (0.70–0.99); 0.04 | |||
OS rate, % | 12 months | 45.6 | 39.5 | |
18 months | 26.2 | 19.3 | ||
PFS, months, median (95% CI) | 7.4 (6.0–7.7) | 5.6 (5.3–5.8) | ||
HR (95% CI); p value | 0.69 (0.58–0.83); < 0.0001 | |||
PFS rate, % | 12 months | 27.4 | 13.9 | |
18 months | 11.4 | 3.6 | ||
ORR, % (95% CI) | 41.8 (36.8–46.9) | 36.2 (31.4–41.2) |
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Abstract Disclosures
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