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)

David Goldstein; Daniel D. Von Hoff; Malcolm Moore; Edward Greeno; Giampaolo Tortora; Ramesh K. Ramanathan; Teresa Macarulla; Helen Liu; Richard Pilot; Stefano Ferrara; Brian Lu

doi:10.1016/j.ejca.2015.10.017

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)

David Goldstein, Daniel D. Von Hoff, Malcolm Moore, Edward Greeno, Giampaolo Tortora, Ramesh K. Ramanathan, Teresa Macarulla, Helen Liu, Richard Pilot, Stefano Ferrara, Brian Lu

Medicine - Hematology, Oncology, Transplant

Research output: Contribution to journal › Article › peer-review

31 Scopus citations

Abstract

Background In 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 methods Patients 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). Results In 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). Conclusions nab-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.

Original language	English (US)
Pages (from-to)	85-91
Number of pages	7
Journal	European Journal of Cancer
Volume	52
DOIs	https://doi.org/10.1016/j.ejca.2015.10.017
State	Published - Jan 2016

Bibliographical note

Funding Information:
The authors thank all participating sites and investigators for their support with the clinical study, as well as Peng Wu for his data programming support. The study was funded by Celgene Corporation. Medical writing assistance was provided by Christopher Carter, PhD, of MediTech Media and funded by Celgene Corporation. All authors had full access to the data and are fully responsible for content and editorial decisions for this manuscript. David Goldstein had final responsibility for the decision to submit for publication.

Publisher Copyright:
© 2015 The Authors.

Keywords

Gemcitabine
Pancreatic cancer
Peripheral neuropathy
nab-Paclitaxel

UN SDGs

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Goldstein, D., Von Hoff, D. D., Moore, M., Greeno, E., Tortora, G., Ramanathan, R. K., Macarulla, T., Liu, H., Pilot, R., Ferrara, S., & Lu, B. (2016). 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). European Journal of Cancer, 52, 85-91. https://doi.org/10.1016/j.ejca.2015.10.017

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). / Goldstein, David; Von Hoff, Daniel D.; Moore, Malcolm et al.
In: European Journal of Cancer, Vol. 52, 01.2016, p. 85-91.

Research output: Contribution to journal › Article › peer-review

Goldstein, D, Von Hoff, DD, Moore, M, Greeno, E, Tortora, G, Ramanathan, RK, Macarulla, T, Liu, H, Pilot, R, Ferrara, S & Lu, B 2016, '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)', European Journal of Cancer, vol. 52, pp. 85-91. https://doi.org/10.1016/j.ejca.2015.10.017

Goldstein D, Von Hoff DD, Moore M, Greeno E, Tortora G, Ramanathan RK et al. 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). European Journal of Cancer. 2016 Jan;52:85-91. doi: 10.1016/j.ejca.2015.10.017

Goldstein, David ; Von Hoff, Daniel D. ; Moore, Malcolm et al. / 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). In: European Journal of Cancer. 2016 ; Vol. 52. pp. 85-91.

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abstract = "Background In 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 methods Patients 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). Results In 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). Conclusions nab-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.",

keywords = "Gemcitabine, Pancreatic cancer, Peripheral neuropathy, nab-Paclitaxel",

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note = "Funding Information: The authors thank all participating sites and investigators for their support with the clinical study, as well as Peng Wu for his data programming support. The study was funded by Celgene Corporation. Medical writing assistance was provided by Christopher Carter, PhD, of MediTech Media and funded by Celgene Corporation. All authors had full access to the data and are fully responsible for content and editorial decisions for this manuscript. David Goldstein had final responsibility for the decision to submit for publication. Publisher Copyright: {\textcopyright} 2015 The Authors.",

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T2 - A subset analysis from a randomised phase III trial (MPACT)

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AU - Von Hoff, Daniel D.

AU - Moore, Malcolm

AU - Greeno, Edward

AU - Tortora, Giampaolo

AU - Ramanathan, Ramesh K.

AU - Macarulla, Teresa

AU - Liu, Helen

AU - Pilot, Richard

AU - Ferrara, Stefano

AU - Lu, Brian

N1 - Funding Information: The authors thank all participating sites and investigators for their support with the clinical study, as well as Peng Wu for his data programming support. The study was funded by Celgene Corporation. Medical writing assistance was provided by Christopher Carter, PhD, of MediTech Media and funded by Celgene Corporation. All authors had full access to the data and are fully responsible for content and editorial decisions for this manuscript. David Goldstein had final responsibility for the decision to submit for publication. Publisher Copyright: © 2015 The Authors.

PY - 2016/1

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N2 - Background In 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 methods Patients 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). Results In 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). Conclusions nab-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.

AB - Background In 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 methods Patients 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). Results In 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). Conclusions nab-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.

KW - Gemcitabine

KW - Pancreatic cancer

KW - Peripheral neuropathy

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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)

Abstract

Bibliographical note

Keywords

UN SDGs

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