NAPOLI-3: NALIRIFOX shows promise as first-line therapy in patients with metastatic pancreatic ductal adenocarcinoma

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  • Metastatic Pancreatic Ductal Andenocarcinoma (mPDAC) is an aggressive type of cancer that is most frequently detected at advanced stages with limited treatment options and a 5-year overall survival of only 11%. There is therefore a critical unmet need to improve the survival and quality of life of these patients. 
  • Presented on the ground in San Francisco during this week’s annual ASCO Gastrointestinal Cancers Symposium, January 19-21, results of the randomized, open-label phase III NAPOLI-3 study (1) show that first-line NALIRIFOX significantly improves overall survival versus standard therapy in patients with mPDAC. 
  • These encouraging data, presented by study lead Zev A. Wainberg, co-Director of the Gastrointestinal Oncology Program at the University of California Los Angeles (UCLA), were co-authored by Teresa Macarulla, Principal Investigator of VHIO’s Gastrointestinal and Endocrine Tumors Group, and a Medical Oncologist at the Vall d’Hebron University Hospital (HUVH – Vall d’Hebron Barcelona Hospital Campus). 

Liposomal irinotecan plus 5-fluorouracil/leucovorin is approved in the USA and Europe for the treatment of patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) with disease progression on gemcitabine-based chemotherapy. Considering the results of a previous phase I/II study (2) that showed encouraging anti-tumor activity of first-line liposomal irinotecan plus 5-fluorouracil/leucovorin and oxaliplatin (NALIRIFOX), the randomized, open-label phase III NAPOLI-3 study (1) was designed to investigate the efficacy and safety of NALIRIFOX versus nab-paclitaxel and gemcitabine in treatment-naïve patients with mPDAC.

“Often diagnosed at advanced stages due to a lack of definitive symptoms, metastatic pancreatic ductal adenocarcinoma is the most common type of pancreatic cancer. It is a notoriously aggressive disease with limited treatment options and a 5-year overall survival of 11%. There is therefore an urgent, unmet clinical need for new and more effective therapies to improve the survival and quality of life of these patients,” says Teresa Macarulla, Principal Investigator of the Vall d’Hebron Institute of Oncology’s (VHIO) Gastrointestinal and Endocrine Tumors Group, and a co-author of the multicenter NAPOLI-3 international study.

Led by Zev A. Wainberg, Professor of Medicine at the University of California, Los Angeles (UCLA) and co-Director of the GI Oncology Program at UCLA, USA, data from this present study were selected to first outing as an oral presentation (1) during this week’s American Society of Clinical Oncology’s (ASCO) 20th Annual Gastrointestinal Cancers Symposium, January 19-21, San Francisco, CA (USA).

NAPOLI-3 included 770 patients with untreated mPDAC who were randomized (1:1) to receive NALIRIFOX or the combination of nab-paclitaxel plus gemcitabine. The primary endpoint of this phase III clinical trial was overall survival (OS), and secondary endpoints were progression-free survival (PFS), overall response rate (ORR), and safety.

Presented today by first author Zev A. Wainberg, results show that at median follow-up of 16.1 months, the median OS was 11.1 months in patients receiving first-line NALIRIFOX compared with 9.2 months in those patients who were treated with the nab-paclitaxel/gemcitabine combination. PFS also significantly improved from 5.6 months to 7.4 months in the NALIRIFOX arm, and the safety profile of NALIRIFOX was manageable and consistent with the profiles of the treatment components.

“Considering the lack of effective treatment strategies and that pancreatic cancer is projected to surpass breast cancer as the third leading cause of cancer death by 2025, there is an urgent need to seek out and develop more effective treatment strategies to improve outcomes for our patients” observes Macarulla, a member of NAPOLI-3’s Scientific Committee.

“Results of this study point to a new therapeutic avenue with NALIFIROX and could represent a step forward as we strive to provide patients with additional, more potent therapies to more successfully combat this devastating disease,” concludes Teresa Macarulla, a Medical Oncologist of the Vall d’Hebron University Hospital’s (HUVH) Medical Oncology Department, headed by VHIO’s Director Josep Tabernero.

 

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References:

 

  1. Abstract #: LBA661– NAPOLI-3: A randomized, open-label phase 3 study of liposomal irinotecan + 5-fluorouracil/leucovorin + oxaliplatin (NALIRIFOX) versus nab-paclitaxel + gemcitabine in treatment-naïve patients with metastatic pancreatic ductal adenocarcinoma (mPDAC). Zev Wainberg, Davide Melisi, Teresa Macarulla, Roberto Pazo-Cid, Sreenivasa Chandana, Christelle De La Fouchardiere, Andrew Dean, Igor Kiss, Woojin Lee, Thorsten Goetze, Eric Van Cutsem, Andrew Paulson, Tanios Bekaii-Saab, Shubham Pant, Richard Hubner, Zhimin Xiao, Huanyu Chen, Fawzi Benzaghou, Eileen O’Reilly.

 

2023 ASCO GI Cancers Symposium Session Details:

Oral Abstract Session Level 3, Ballroom

Oral Abstract Session B: Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract

Primary Track: Pancreatic Cancer

Presenter: Zev A. Wainberg, MD | UCLA Medical Center–Santa Monica

Date: 20 January

Time: 22:30h CET

 

  1. Wainberg ZA, Bekaii-Saab T, Boland PM, Dayyani F, Macarulla T, Mody K, Belanger B, Maxwell F, Moore Y, Thiagalingam A, Wang T, Zhang B, Dean A. First-line liposomal irinotecan with oxaliplatin, 5-fluorouracil and leucovorin (NALIRIFOX) in pancreatic ductal adenocarcinoma: A phase I/II study. Eur J Cancer. 2021 Jul;151:14-24.

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