Second-line therapy after nab-paclitaxel plus gemcitabine or after gemcitabine for patients with metastatic pancreatic cancer

E Gabriela Chiorean, Daniel D Von Hoff, Josep Tabernero, Robert El-Maraghi, Wen Wee Ma, Michele Reni, Marion Harris, Robert Whorf, Helen Liu, Jack Shiansong Li, Victoria Manax, Alfredo Romano, Brian Lu, David Goldstein, E Gabriela Chiorean, Daniel D Von Hoff, Josep Tabernero, Robert El-Maraghi, Wen Wee Ma, Michele Reni, Marion Harris, Robert Whorf, Helen Liu, Jack Shiansong Li, Victoria Manax, Alfredo Romano, Brian Lu, David Goldstein

Abstract

Background: This exploratory analysis evaluated second-line (2L) therapy for metastatic pancreatic cancer in a large phase 3 trial (MPACT).

Methods: Patients who received first-line (1L) nab-paclitaxel+gemcitabine (nab-P+Gem) or Gem were assessed for survival based on 2L treatment received. Multivariate analyses tested influence of treatment effect and prognostic factors on survival.

Results: The majority of 2L treatments (267 out of 347, 77%) contained a fluoropyrimidine (5-fluorouracil or capecitabine). Median total survival (1L randomisation to death) for patients who received 2L treatment after 1L nab-P+Gem vs Gem alone was 12.8 vs 9.9 months (P=0.015). Median total survival for patients with a fluoropyrimidine-containing 2L therapy after nab-P+Gem vs Gem was 13.5 vs 9.5 months (P=0.012). Median 2L survival (duration from start of 2L therapy to death) was 5.3 vs 4.5 months for nab-P+Gem vs Gem, respectively (P=0.886). Factors significantly associated with longer post-1L survival by multivariate analyses included 1L nab-P+Gem, receiving 2L treatment, longer 1L progression-free survival, and Karnofsky performance status⩾70 and neutrophil-to-lymphocyte ratio⩽5 at the end of 1L treatment.

Conclusions: These findings support the use of 2L therapy for patients with metastatic pancreatic cancer. Fluoropyrimidine-containing treatment after 1L nab-P+Gem is an active regimen with significant clinical effect.

Conflict of interest statement

EGC: research funding, consultant or advisory role, Celgene. DDVH: consultant or advisory role, honoraria, Celgene; research funding, HonorHealth. JT: consultant or advisory role, honoraria, Celgene. RE-M: consultant or advisory role, research funding, Celgene. WWM: research funding, Celgene. MR: consultant or advisory role, honoraria, research funding, Celgene. MH and RW: nothing to disclose. HL, JSL, VM, AR and BL: employment, stock ownership, Celgene. DG: research funding, Celgene, Pfizer; consultant or advisory role (unremunerated), Celgene, Pfizer.

Figures

Figure 1
Figure 1
Total OS in patients who received 2L therapy. Gem=gemcitabine; HR=hazard ratio; nab-P=nab-paclitaxel.
Figure 2
Figure 2
Forest plot of total OS in subgroups defined by 2L therapy. FOLFIRINOX=folinic acid, 5-fluorouracil, irinotecan, and oxaliplatin; FOLFOX=folinic acid, 5-FU, and oxaliplatin; Gem=gemcitabine; HR=hazard ratio; mono=monotherapy; nab-P=nab-paclitaxel; OFF=oxaliplatin, folinic acid, and 5-FU.
Figure 3
Figure 3
Second-line OS (OS2), defined as survival time from the start of 2L therapy to death, in patients who received 2L therapy. Gem=gemcitabine; HR=hazard ratio; nab-P=nab-paclitaxel.

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Source: PubMed

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