A randomized phase II study evaluating different maintenance schedules of nab-paclitaxel in the first-line treatment of metastatic breast cancer: Final results of the IBCSG 42-12/BIG 2-12 SNAP trial

on behalf of the International Breast Cancer Study Group, Cancer Trials Ireland and SOLTI Group

Research output: Contribution to journalArticle

Abstract

Background: The phase II SNAP trial was designed to evaluate the efficacy of alternative chemotherapy schedules for prolonged administration in HER2-negative metastatic breast cancer (MBC), after a short induction at conventional doses. Patients and methods: Between April 2013 and August 2015, 258 women untreated with chemotherapy for MBC were randomly assigned to receive three different maintenance chemotherapy schedules after three cycles of identical induction chemotherapy: arm A, nab-paclitaxel 150 mg/m2 days 1 and 15 Q28; arm B, nab-paclitaxel 100 mg/m2 days 1, 8 and 15 Q28; arm C, nab-paclitaxel 75 mg/m2 days 1, 8, 15 and 22 Q28. Induction was three cycles nab-paclitaxel 150/125 mg/m2, days 1, 8 and 15 Q28. The primary objective was to evaluate the efficacy of each maintenance schedule, in terms of progression-free survival (PFS), as compared with the historical reference of 7-month median PFS reported by previous studies with first-line docetaxel. One-sample, one-sided log-rank tests were utilized. Quality-of-life (QoL) evaluation was carried out, and the global indicator for physical well-being was defined as the primary QoL end point; completion rates of QoL forms were >90%. Results: In total, 255 patients were assessable for the primary end point. After 18.2-month median follow-up, 182 PFS events were observed. Median PFS was 7.9 months [90% confidence interval CI 6.8-8.4] in arm A, 9.0 months (90% CI 8.1-10.9) in arm B and 8.5 months (90% CI 6.7-9.5) in arm C. PFS in arm B was significantly longer than the historical reference of first-line docetaxel (P=0.03). Grade≥2 sensory neuropathy was reported in 37.9%, 36.1% and 31.2% of the patients in arm A, B and C, respectively (Grade≥3 in 9.1%, 5.6% and 6.6% of the patients, respectively). Noteworthy, the QoL scores for sensory neuropathy did not worsen with prolonged nab-paclitaxel administration in any of the maintenance arms. Conclusion: The SNAP trial demonstrated that alternative nab-paclitaxel maintenance schedules with reduced dosages after a short induction at conventional doses are feasible and active in the first-line treatment of MBC. Registration: ClinicalTrials.gov NCT01746225

Original languageEnglish
Article numbermdx821
Pages (from-to)661-668
Number of pages8
JournalAnnals of Oncology
Volume29
Issue number3
DOIs
Publication statusPublished - Mar 1 2018

Fingerprint

Appointments and Schedules
Disease-Free Survival
Maintenance
docetaxel
Breast Neoplasms
Quality of Life
Therapeutics
Maintenance Chemotherapy
Drug Therapy
Induction Chemotherapy
130-nm albumin-bound paclitaxel
Confidence Intervals

Keywords

  • Alternative treatment schedules
  • Maintenance chemotherapy
  • Metastatic breast cancer

ASJC Scopus subject areas

  • Hematology
  • Oncology

Cite this

A randomized phase II study evaluating different maintenance schedules of nab-paclitaxel in the first-line treatment of metastatic breast cancer : Final results of the IBCSG 42-12/BIG 2-12 SNAP trial. / on behalf of the International Breast Cancer Study Group; Cancer Trials Ireland and SOLTI Group.

In: Annals of Oncology, Vol. 29, No. 3, mdx821, 01.03.2018, p. 661-668.

Research output: Contribution to journalArticle

@article{183322628939488cb4f958543d55c4fe,
title = "A randomized phase II study evaluating different maintenance schedules of nab-paclitaxel in the first-line treatment of metastatic breast cancer: Final results of the IBCSG 42-12/BIG 2-12 SNAP trial",
abstract = "Background: The phase II SNAP trial was designed to evaluate the efficacy of alternative chemotherapy schedules for prolonged administration in HER2-negative metastatic breast cancer (MBC), after a short induction at conventional doses. Patients and methods: Between April 2013 and August 2015, 258 women untreated with chemotherapy for MBC were randomly assigned to receive three different maintenance chemotherapy schedules after three cycles of identical induction chemotherapy: arm A, nab-paclitaxel 150 mg/m2 days 1 and 15 Q28; arm B, nab-paclitaxel 100 mg/m2 days 1, 8 and 15 Q28; arm C, nab-paclitaxel 75 mg/m2 days 1, 8, 15 and 22 Q28. Induction was three cycles nab-paclitaxel 150/125 mg/m2, days 1, 8 and 15 Q28. The primary objective was to evaluate the efficacy of each maintenance schedule, in terms of progression-free survival (PFS), as compared with the historical reference of 7-month median PFS reported by previous studies with first-line docetaxel. One-sample, one-sided log-rank tests were utilized. Quality-of-life (QoL) evaluation was carried out, and the global indicator for physical well-being was defined as the primary QoL end point; completion rates of QoL forms were >90{\%}. Results: In total, 255 patients were assessable for the primary end point. After 18.2-month median follow-up, 182 PFS events were observed. Median PFS was 7.9 months [90{\%} confidence interval CI 6.8-8.4] in arm A, 9.0 months (90{\%} CI 8.1-10.9) in arm B and 8.5 months (90{\%} CI 6.7-9.5) in arm C. PFS in arm B was significantly longer than the historical reference of first-line docetaxel (P=0.03). Grade≥2 sensory neuropathy was reported in 37.9{\%}, 36.1{\%} and 31.2{\%} of the patients in arm A, B and C, respectively (Grade≥3 in 9.1{\%}, 5.6{\%} and 6.6{\%} of the patients, respectively). Noteworthy, the QoL scores for sensory neuropathy did not worsen with prolonged nab-paclitaxel administration in any of the maintenance arms. Conclusion: The SNAP trial demonstrated that alternative nab-paclitaxel maintenance schedules with reduced dosages after a short induction at conventional doses are feasible and active in the first-line treatment of MBC. Registration: ClinicalTrials.gov NCT01746225",
keywords = "Alternative treatment schedules, Maintenance chemotherapy, Metastatic breast cancer",
author = "{on behalf of the International Breast Cancer Study Group} and {Cancer Trials Ireland and SOLTI Group} and Alessandra Gennari and Z. Sun and U. Hasler-Strub and M. Colleoni and Kennedy, {M. J.} and {Von Moos}, R. and J. Cort{\'e}s and Vidal, {M. J.} and B. Hennessy and J. Walshe and {Amillano Parraga}, K. and K. Ribi and J. Bernhard and {Morales Murillo}, S. and O. Pagani and A. Barbeaux and S. Borstnar and M. Rabaglio-Poretti and R. Maibach and Regan, {M. M.} and G. Jerusalem",
year = "2018",
month = "3",
day = "1",
doi = "10.1093/annonc/mdx772",
language = "English",
volume = "29",
pages = "661--668",
journal = "Annals of Oncology",
issn = "0923-7534",
publisher = "NLM (Medline)",
number = "3",

}

TY - JOUR

T1 - A randomized phase II study evaluating different maintenance schedules of nab-paclitaxel in the first-line treatment of metastatic breast cancer

T2 - Final results of the IBCSG 42-12/BIG 2-12 SNAP trial

AU - on behalf of the International Breast Cancer Study Group

AU - Cancer Trials Ireland and SOLTI Group

AU - Gennari, Alessandra

AU - Sun, Z.

AU - Hasler-Strub, U.

AU - Colleoni, M.

AU - Kennedy, M. J.

AU - Von Moos, R.

AU - Cortés, J.

AU - Vidal, M. J.

AU - Hennessy, B.

AU - Walshe, J.

AU - Amillano Parraga, K.

AU - Ribi, K.

AU - Bernhard, J.

AU - Morales Murillo, S.

AU - Pagani, O.

AU - Barbeaux, A.

AU - Borstnar, S.

AU - Rabaglio-Poretti, M.

AU - Maibach, R.

AU - Regan, M. M.

AU - Jerusalem, G.

PY - 2018/3/1

Y1 - 2018/3/1

N2 - Background: The phase II SNAP trial was designed to evaluate the efficacy of alternative chemotherapy schedules for prolonged administration in HER2-negative metastatic breast cancer (MBC), after a short induction at conventional doses. Patients and methods: Between April 2013 and August 2015, 258 women untreated with chemotherapy for MBC were randomly assigned to receive three different maintenance chemotherapy schedules after three cycles of identical induction chemotherapy: arm A, nab-paclitaxel 150 mg/m2 days 1 and 15 Q28; arm B, nab-paclitaxel 100 mg/m2 days 1, 8 and 15 Q28; arm C, nab-paclitaxel 75 mg/m2 days 1, 8, 15 and 22 Q28. Induction was three cycles nab-paclitaxel 150/125 mg/m2, days 1, 8 and 15 Q28. The primary objective was to evaluate the efficacy of each maintenance schedule, in terms of progression-free survival (PFS), as compared with the historical reference of 7-month median PFS reported by previous studies with first-line docetaxel. One-sample, one-sided log-rank tests were utilized. Quality-of-life (QoL) evaluation was carried out, and the global indicator for physical well-being was defined as the primary QoL end point; completion rates of QoL forms were >90%. Results: In total, 255 patients were assessable for the primary end point. After 18.2-month median follow-up, 182 PFS events were observed. Median PFS was 7.9 months [90% confidence interval CI 6.8-8.4] in arm A, 9.0 months (90% CI 8.1-10.9) in arm B and 8.5 months (90% CI 6.7-9.5) in arm C. PFS in arm B was significantly longer than the historical reference of first-line docetaxel (P=0.03). Grade≥2 sensory neuropathy was reported in 37.9%, 36.1% and 31.2% of the patients in arm A, B and C, respectively (Grade≥3 in 9.1%, 5.6% and 6.6% of the patients, respectively). Noteworthy, the QoL scores for sensory neuropathy did not worsen with prolonged nab-paclitaxel administration in any of the maintenance arms. Conclusion: The SNAP trial demonstrated that alternative nab-paclitaxel maintenance schedules with reduced dosages after a short induction at conventional doses are feasible and active in the first-line treatment of MBC. Registration: ClinicalTrials.gov NCT01746225

AB - Background: The phase II SNAP trial was designed to evaluate the efficacy of alternative chemotherapy schedules for prolonged administration in HER2-negative metastatic breast cancer (MBC), after a short induction at conventional doses. Patients and methods: Between April 2013 and August 2015, 258 women untreated with chemotherapy for MBC were randomly assigned to receive three different maintenance chemotherapy schedules after three cycles of identical induction chemotherapy: arm A, nab-paclitaxel 150 mg/m2 days 1 and 15 Q28; arm B, nab-paclitaxel 100 mg/m2 days 1, 8 and 15 Q28; arm C, nab-paclitaxel 75 mg/m2 days 1, 8, 15 and 22 Q28. Induction was three cycles nab-paclitaxel 150/125 mg/m2, days 1, 8 and 15 Q28. The primary objective was to evaluate the efficacy of each maintenance schedule, in terms of progression-free survival (PFS), as compared with the historical reference of 7-month median PFS reported by previous studies with first-line docetaxel. One-sample, one-sided log-rank tests were utilized. Quality-of-life (QoL) evaluation was carried out, and the global indicator for physical well-being was defined as the primary QoL end point; completion rates of QoL forms were >90%. Results: In total, 255 patients were assessable for the primary end point. After 18.2-month median follow-up, 182 PFS events were observed. Median PFS was 7.9 months [90% confidence interval CI 6.8-8.4] in arm A, 9.0 months (90% CI 8.1-10.9) in arm B and 8.5 months (90% CI 6.7-9.5) in arm C. PFS in arm B was significantly longer than the historical reference of first-line docetaxel (P=0.03). Grade≥2 sensory neuropathy was reported in 37.9%, 36.1% and 31.2% of the patients in arm A, B and C, respectively (Grade≥3 in 9.1%, 5.6% and 6.6% of the patients, respectively). Noteworthy, the QoL scores for sensory neuropathy did not worsen with prolonged nab-paclitaxel administration in any of the maintenance arms. Conclusion: The SNAP trial demonstrated that alternative nab-paclitaxel maintenance schedules with reduced dosages after a short induction at conventional doses are feasible and active in the first-line treatment of MBC. Registration: ClinicalTrials.gov NCT01746225

KW - Alternative treatment schedules

KW - Maintenance chemotherapy

KW - Metastatic breast cancer

UR - http://www.scopus.com/inward/record.url?scp=85042659342&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85042659342&partnerID=8YFLogxK

U2 - 10.1093/annonc/mdx772

DO - 10.1093/annonc/mdx772

M3 - Article

C2 - 29228091

AN - SCOPUS:85042659342

VL - 29

SP - 661

EP - 668

JO - Annals of Oncology

JF - Annals of Oncology

SN - 0923-7534

IS - 3

M1 - mdx821

ER -