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EFFECT: A randomized phase II study of efficacy and impact on function of two doses of nab-paclitaxel as first-line treatment in older women with advanced breast cancer
Laura Biganzoli
Nuovo Ospedale di Prato S.Stefano
Corresponding Author
ORCiD: https://orcid.org/0000-0001-7989-8658
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published version at Breast Cancer Research.
Background: Limited data are available regarding the use of nab-paclitaxel in older patients with breast cancer. A weekly schedule is recommended, but there is a paucity of evidence regarding the optimal dose. We evaluated the efficacy of two different doses of weekly nab-paclitaxel, with a specific focus on their corresponding impact on patient function, in order to address the lack of data specifically relating to the older population.
Methods: EFFECT is an open-label, phase II trial wherein 160 women with advanced breast cancer aged ≥ 65 years were enrolled from 15 institutions within Italy. Patients were randomly assigned 1:1 to receive nab-paclitaxel 100 mg/m2 (Arm A) or 125 mg/m2 (Arm B) on days 1,8,15 on a 28-day cycle, as first-line treatment for advanced disease. The primary endpoint was event-free survival (EFS), wherein an event was defined as disease progression (PD), functional decline (FD) or death. In each arm, the null hypothesis that the median EFS would be ≤7 months was tested against a one-sided alternative according to the Brookmeyer Crowley test. Secondary endpoints included objective response rate (ORR), clinical benefit rate (CBR), progression-free survival (PFS), overall survival (OS), and safety.
Results: After a median follow-up of 32.6 months, 140 events were observed in 158 evaluable patients. Median EFS was 8.2 months (90% CI, 5.9-8.9; p=0.188) in Arm A, versus 8.3 months (90% CI, 6.2-9.7; p=0.078) in Arm B. Progression-free survival, overall survival and response rates were similar in both groups. A higher percentage of dose reductions and discontinuations due to adverse events (AEs) was noted in Arm B. The most frequently reported non-hematological AEs were fatigue (grade [G] 2-3 toxicity occurrence in Arm A versus B: 43% and 51%, respectively) and peripheral neuropathy (G2-3 Arm A versus B: 19% and 38%, respectively).
Conclusion: Pre-specified outcomes were similar in both treatment arms. However, 100 mg/m2 was significantly better tolerated with fewer neurotoxicity-related events, representing a more feasible dose to be recommended for older patients with advanced disease.
Trial registration
EudraCT identifier: 2012-002707-18, registered June 4 2012 - https://www.clinicaltrialsregister.eu/ctr-search/trial/2012-002707-18/IT#E . NIH ClinicalTrials.gov identifier: NCT02783222, registered May 26 2016 – retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02783222
Keywords
nab-paclitaxel, functional decline, toxicity, breast cancer, older adults, metastatic
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CURRENT STATUS: Published
Version 2
Posted 02 Jun, 2020
Published
On 05 Aug, 2020
No community comments so far
Editorial decision: Accept
On 20 Jul, 2020
Reviewers invited
Invitations sent on 01 Jun, 2020
Reviewer #1 agreed
On 01 Jun, 2020
Review #1 received
Received 01 Jun, 2020
Editor invited
On 24 May, 2020
Editor assigned
On 24 May, 2020
Submission checks complete
On 23 May, 2020
No comments provided
Editorial decision: Major Revision
On 13 Apr, 2020
Review #2 received
Received 05 Apr, 2020
Review #1 received
Received 05 Apr, 2020
Reviewer #2 agreed
On 29 Mar, 2020
Reviewer #1 agreed
On 09 Mar, 2020
Reviewers invited
Invitations sent on 09 Mar, 2020
Editor assigned
On 21 Feb, 2020
First submitted
On 20 Feb, 2020
Submission checks complete
On 20 Feb, 2020
Editor invited
On 20 Feb, 2020
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This preprint is under consideration at Breast Cancer Research. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
EFFECT: A randomized phase II study of efficacy and impact on function of two doses of nab-paclitaxel as first-line treatment in older women with advanced breast cancer
Laura Biganzoli
Nuovo Ospedale di Prato S.Stefano
Corresponding Author
ORCiD: https://orcid.org/0000-0001-7989-8658
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
Version 2
Posted 02 Jun, 2020
Published
On 05 Aug, 2020
No community comments so far
Editorial decision: Accept
On 20 Jul, 2020
Reviewers invited
Invitations sent on 01 Jun, 2020
Reviewer #1 agreed
On 01 Jun, 2020
Review #1 received
Received 01 Jun, 2020
Editor invited
On 24 May, 2020
Editor assigned
On 24 May, 2020
Submission checks complete
On 23 May, 2020
No comments provided
Editorial decision: Major Revision
On 13 Apr, 2020
Review #2 received
Received 05 Apr, 2020
Review #1 received
Received 05 Apr, 2020
Reviewer #2 agreed
On 29 Mar, 2020
Reviewer #1 agreed
On 09 Mar, 2020
Reviewers invited
Invitations sent on 09 Mar, 2020
Editor assigned
On 21 Feb, 2020
First submitted
On 20 Feb, 2020
Submission checks complete
On 20 Feb, 2020
Editor invited
On 20 Feb, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published version at Breast Cancer Research.
Background: Limited data are available regarding the use of nab-paclitaxel in older patients with breast cancer. A weekly schedule is recommended, but there is a paucity of evidence regarding the optimal dose. We evaluated the efficacy of two different doses of weekly nab-paclitaxel, with a specific focus on their corresponding impact on patient function, in order to address the lack of data specifically relating to the older population.
Methods: EFFECT is an open-label, phase II trial wherein 160 women with advanced breast cancer aged ≥ 65 years were enrolled from 15 institutions within Italy. Patients were randomly assigned 1:1 to receive nab-paclitaxel 100 mg/m2 (Arm A) or 125 mg/m2 (Arm B) on days 1,8,15 on a 28-day cycle, as first-line treatment for advanced disease. The primary endpoint was event-free survival (EFS), wherein an event was defined as disease progression (PD), functional decline (FD) or death. In each arm, the null hypothesis that the median EFS would be ≤7 months was tested against a one-sided alternative according to the Brookmeyer Crowley test. Secondary endpoints included objective response rate (ORR), clinical benefit rate (CBR), progression-free survival (PFS), overall survival (OS), and safety.
Results: After a median follow-up of 32.6 months, 140 events were observed in 158 evaluable patients. Median EFS was 8.2 months (90% CI, 5.9-8.9; p=0.188) in Arm A, versus 8.3 months (90% CI, 6.2-9.7; p=0.078) in Arm B. Progression-free survival, overall survival and response rates were similar in both groups. A higher percentage of dose reductions and discontinuations due to adverse events (AEs) was noted in Arm B. The most frequently reported non-hematological AEs were fatigue (grade [G] 2-3 toxicity occurrence in Arm A versus B: 43% and 51%, respectively) and peripheral neuropathy (G2-3 Arm A versus B: 19% and 38%, respectively).
Conclusion: Pre-specified outcomes were similar in both treatment arms. However, 100 mg/m2 was significantly better tolerated with fewer neurotoxicity-related events, representing a more feasible dose to be recommended for older patients with advanced disease.
Trial registration
EudraCT identifier: 2012-002707-18, registered June 4 2012 - https://www.clinicaltrialsregister.eu/ctr-search/trial/2012-002707-18/IT#E . NIH ClinicalTrials.gov identifier: NCT02783222, registered May 26 2016 – retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02783222
Figure 1
Figure 2