First-line NALIRIFOX regimen ups survival in metastatic pancreatic cancer

The use of liposomal irinotecan in combination with 5-fluorouracil, leucovorin, and oxaliplatin (NALIRIFOX regimen) significantly improved overall survival (OS) and progression-free survival (PFS) in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) compared with gemcitabine plus nab-paclitaxel (Gem+NabP) in the first-line setting, according to the NAPOLI-3* trial presented at the ASCO GI 2023.

The trial met its primary endpoint, with NALIRIFOX demonstrating a statistically significant and clinically meaningful improvement in OS among previously untreated patients with mPDAC compared with Gem+NabP, said Dr Zev Wainberg from the University of California in Los Angeles, California, US. [ASCO GI 2023, abstract LBA661]

It also met its key secondary endpoint of PFS, with a manageable safety profile consistent with what was shown in the phase I/II study, he added.

At a median follow-up of 16.1 months, patients who received NALIRIFOX had a significantly longer median OS (11.1 vs 9.2 months; hazard ratio [HR], 0.83; p=0.04) and PFS (7.4 vs 5.6 months; HR, 0.69; p<0.0001) than those who received Gem+NabP.

“For the first time, a clinical study in the first-line setting for mPDAC demonstrated superior OS and PFS for an investigational [novel NALIRIFOX] regimen when compared to standard of care treatment with Gem+NabP,” said Wainberg in a press release. [https://www.ipsen.com/press-releases/ipsen-presents-phase-iii-napoli-3-trial-of-onivyde-regimen-demonstrating-positive-survival-results-in-previously-untreated-metastatic-pancreatic-ductal-adenocarcinoma-at-asco-gi/]

This open-label, phase III trial involved 770 patients with previously untreated mPDAC who were randomized to receive either the NALIRIFOX regimen** twice a month (n=383; mean age 64 years) or Gem+NabP*** thrice a month (n=387; mean age 65 years).

At baseline, the majority of participants had liver metastatic disease (80.2 percent in the NALIRIFOX arm and 80.4 percent in the Gem+NabP arm). About 41–43 percent of patients in both arms had an ECOG performance status (PS) 0, while 56-58 percent had an ECOG PS 1.

The OS and PFS benefits with NALIRIFOX vs Gem+NabP were generally consistent regardless of ECOG PS 0/1, geographic region, and presence or absence of liver metastatic disease, Wainberg noted.

Objective response rate, another secondary endpoint, was higher in the NALIRIFOX arm than in the Gem+NabP arm (41.8 percent vs 36.2 percent). Disease progression rate was lower with the former vs the latter regimen (9.9 percent vs 14.5 percent).

In terms of safety, the overall rates of treatment-emergent adverse events (TEAEs) were similar between the NALIRIFOX and Gem+NabP arms (99.7 percent vs 99.2 percent).

Grade ≥3 TEAE rates were also comparable in both the NALIRIFOX and Gem+NabP arms (87.0 percent vs 86.0 percent), as were the rates of serious TEAEs (54.3 percent and 51.1 percent) and TEAEs leading to death (5.9 percent vs 6.1 percent).

However, NALIRIFOX recipients experienced more non-haematologic toxicities, particularly diarrhoea (20.3 percent vs 4.5 percent), nausea (11.9 percent vs 2.6 percent), and vomiting (7.0 percent vs 2.1 percent), than Gem+NabP recipients.

Nonetheless, the safety profile of NALIRIFOX was manageable, with no new safety signals identified, Wainberg noted.

“These findings are especially meaningful to people living with this aggressive and difficult-to-treat cancer, representing the potential to prolong life with a safety profile consistent with the safety profile of the treatment components,” Wainberg said in a press release.

“These results support the NALIRIFOX regimen as a new reference regimen for the first-line treatment of patients with mPDAC,” he added.

*NAPOLI-3: A study to assess the effectiveness and safety of irinotecan liposome injection, 5-fluorouracil/leucovorin plus oxaliplatin in patients not previously treated for metastatic pancreatic cancer, compared to nab-paclitaxel+gemcitabine treatment

**Liposomal irinotecan 50 mg/m², 5-FU 2,400 mg/m², leucovorin 400 mg/m², and oxaliplatin 60 mg/m² on days 1 and 15 for a 28-day cycle