Development of peripheral neuropathy and its association with survival during treatment with nab-paclitaxel plus gemcitabine for patients with metastatic adenocarcinoma of the pancreas: A subset analysis from a randomised phase III trial (MPACT)
Affiliation:
1. Prince of Wales Hospital, Department of Oncology, South Eastern Sydney Illawarra, NSW Health, Barker Street, Randwick, NSW 2031, Australia;2. Scottsdale Healthcare/TGen, Bisgrove Research Pavilion, 10510 North 92nd Street, Suite 200, Scottsdale, AZ 85258, USA;3. Princess Margaret Hospital, 5th Floor 708, 610 University Avenue, Toronto, Ontario M5G2M9, Canada;4. University of Minnesota, Division of Hematology, Oncology and Transplantation, 420 Delaware Street SE, MMC 480, Minneapolis, MN 55455, USA;5. Azienda Ospedaliera Universitaria Integrata di Verona, Policlinico Borgo Roma, Piazzale L. Scuro, 10, 37134 Verona, Italy;6. Mayo Clinic, 13400 E Shea Blvd FL 3, Scottsdale, AZ 85259, USA;7. Vall d''Hebron University Hospital, Vall d''Hebron Institute of Oncology (VHIO), P. Vall d''Hebron 119-129, Barcelona, Spain;8. Celgene Corporation, 86 Morris Avenue, Summit, NJ 07901, USA;9. University of New South Wales, Australia
Abstract:
BackgroundIn a phase III trial in patients with metastatic pancreatic cancer (MPC), nab-paclitaxel plus gemcitabine (nab-P/Gem) demonstrated greater efficacy but higher rates of peripheral neuropathy (PN) versus Gem. This exploratory analysis aimed to characterise the frequency, duration, and severity of PN with nab-P/Gem in the MPACT study.Patients and methodsPatients with previously untreated MPC received nab-P/Gem or Gem. PN was evaluated using a broad-spectrum group of Standardised Medical Dictionary for Regulatory Activities Queries (SMQ) and graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.0. A case report form was completed by physicians on day 1 of each cycle (also graded by NCI CTCAE version 3.0).ResultsIn the nab-P/Gem arm, 227/421 patients (54%) experienced any-grade PN and 70 (17%) experienced grade III PN. No grade IV PN was reported. Most early-onset PN events were grade I, and treatment-related grade III PN occurred in 7% of patients who received up to three cycles of nab-P. Of those who developed grade III PN with nab-P/Gem treatment, 30 (43%) improved to grade ≤I (median time to improvement = 29 days) and 31 (44%) resumed therapy. Development of PN was associated with efficacy; median overall survival in patients with grade III versus 0 PN was 14.9 versus 5.9 months (hazard ratio, 0.33; P < .0001).Conclusionsnab-P/Gem was associated with grade III PN in a small percentage of patients. PN development was associated with longer treatment duration and improved survival. Grade III PN was reversible to grade ≤I in many patients (median ≈ 1 month) NCT00844649.
