CA19-9 decrease at 8 weeks as a predictor of overall survival in a randomized phase III trial (MPACT) of weekly nab-paclitaxel plus gemcitabine versus gemcitabine alone in patients with metastatic pancreatic cancer

E G Chiorean, D D Von Hoff, M Reni, F P Arena, J R Infante, V G Bathini, T E Wood, P N Mainwaring, R T Muldoon, P R Clingan, V Kunzmann, R K Ramanathan, J Tabernero, D Goldstein, D McGovern, B Lu, A Ko, E G Chiorean, D D Von Hoff, M Reni, F P Arena, J R Infante, V G Bathini, T E Wood, P N Mainwaring, R T Muldoon, P R Clingan, V Kunzmann, R K Ramanathan, J Tabernero, D Goldstein, D McGovern, B Lu, A Ko

Abstract

Background: A phase I/II study and subsequent phase III study (MPACT) reported significant correlations between CA19-9 decreases and prolonged overall survival (OS) with nab-paclitaxel plus gemcitabine (nab-P + Gem) treatment for metastatic pancreatic cancer (MPC). CA19-9 changes at week 8 and potential associations with efficacy were investigated as part of an exploratory analysis in the MPACT trial.

Patients and methods: Untreated patients with MPC (N = 861) received nab-P + Gem or Gem alone. CA19-9 was evaluated at baseline and every 8 weeks.

Results: Patients with baseline and week-8 CA19-9 measurements were analyzed (nab-P + Gem: 252; Gem: 202). In an analysis pooling the treatments, patients with any CA19-9 decline (80%) versus those without (20%) had improved OS (median 11.1 versus 8.0 months; P = 0.005). In the nab-P + Gem arm, patients with (n = 206) versus without (n = 46) any CA19-9 decrease at week 8 had a confirmed overall response rate (ORR) of 40% versus 13%, and a median OS of 13.2 versus 8.3 months (P = 0.001), respectively. In the Gem-alone arm, patients with (n = 159) versus without (n = 43) CA19-9 decrease at week 8 had a confirmed ORR of 15% versus 5%, and a median OS of 9.4 versus 7.1 months (P = 0.404), respectively. In the nab-P + Gem and Gem-alone arms, by week 8, 16% (40/252) and 6% (13/202) of patients, respectively, had an unconfirmed radiologic response (median OS 13.7 and 14.7 months, respectively), and 79% and 84% of patients, respectively, had stable disease (SD) (median OS 11.1 and 9 months, respectively). Patients with SD and any CA19-9 decrease (158/199 and 133/170) had a median OS of 13.2 and 9.4 months, respectively.

Conclusion: This analysis demonstrated that, in patients with MPC, any CA19-9 decrease at week 8 can be an early marker for chemotherapy efficacy, including in those patients with SD. CA19-9 decrease identified more patients with survival benefit than radiologic response by week 8.

Keywords: CA19-9; MPACT; chemotherapy; nab-paclitaxel; pancreatic cancer.

© The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology.

Figures

Figure 1.
Figure 1.
OS in patients with any, ≥20%, ≥60%, and ≥90% CA19-9 level decreases from baseline at week 8. Kaplan–Meier survival curves for patients with any (A), ≥20% (B), ≥60% (C), and ≥90% (D) reductions in CA19-9 level from baseline at week 8. Gem, gemcitabine; HR, hazard ratio; nab-P, nab-paclitaxel.
Figure 2.
Figure 2.
Decrease from baseline over time (velocity) in CA19-9 level for evaluable patients on study treatment. CA19-9 levels were measured at baseline and every 8 weeks. Gem, gemcitabine; nab-P, nab-paclitaxel.

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Source: PubMed

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