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Research Article
William M Sikov
Women and Infants Hospital of Rhode Island
Corresponding Author
ORCiD: https://orcid.org/0000-0001-5451-6449
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Purpose:
In HER2-positive breast cancer (HER2+BC), neoadjuvant chemotherapy (NACT) with dual HER2-targeted therapy achieves high pathologic complete response (pCR) rates. Anthracycline-free NACT regimens avoid toxicities associated with anthracyclines, but every 3-week TCHP also has substantial side effects. We hypothesized that a weekly regimen might have equivalent efficacy with less toxicity; we also investigated whether poorly responding patients would benefit from switching to AC.
Methods:
Patients with clinical stage II-III HER2+BC received weekly paclitaxel 80 mg/m2 and carboplatin AUC2 with every 3-week trastuzumab and pertuzumab (wPCbTP), with the option of splitting the pertuzumab loading dose. After 12 weeks, responding patients continued wPCbTP for another 6 weeks, while non-responders switched to AC. Dose modifications and post-op therapy were at investigator discretion.
Results:
In 30 evaluable patients, the pCR rate was 77% (95% CI 58-90%); 12/14 (86%) in ER-negative and 11/16 (69%) in ER-positive. Only two patients transitioned to AC for non-response, of which one achieved pCR. There were no episodes of febrile neutropenia or grade >3 peripheral neuropathy, though several patients who continued wPCbTP stopped before week 18. Split-dose pertuzumab was associated with less grade >2 diarrhea (40%) than the standard loading dose (60%).
Conclusions:
pCR rates with our regimen were as high as reported with TCHP with fewer grade >3 toxicities, though diarrhea remains a concern. Too few patients had a suboptimal response to adequately test switching to AC. The wPCbTP regimen should be considered an alternative to TCHP as neoadjuvant therapy for HER2+BC.
ClinicalTrials.gov identifier: NCT02789657
Keywords
Breast cancer, early stage, HER2-positive breast cancer, neoadjuvant chemotherapy, carboplatin
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A new preprint design is coming!
We have improved readability, clarity, accessibility, and opportunities for engagement.
This preprint is under consideration at Breast Cancer Research and Treatment. 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
William M Sikov
Women and Infants Hospital of Rhode Island
Corresponding Author
ORCiD: https://orcid.org/0000-0001-5451-6449
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: Under Review
Version 1
Posted 24 Mar, 2021
No community comments so far
Reviews received
Received 20 Mar, 2021
Editor assigned
On 18 Mar, 2021
First submitted
On 18 Mar, 2021
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Purpose:
In HER2-positive breast cancer (HER2+BC), neoadjuvant chemotherapy (NACT) with dual HER2-targeted therapy achieves high pathologic complete response (pCR) rates. Anthracycline-free NACT regimens avoid toxicities associated with anthracyclines, but every 3-week TCHP also has substantial side effects. We hypothesized that a weekly regimen might have equivalent efficacy with less toxicity; we also investigated whether poorly responding patients would benefit from switching to AC.
Methods:
Patients with clinical stage II-III HER2+BC received weekly paclitaxel 80 mg/m2 and carboplatin AUC2 with every 3-week trastuzumab and pertuzumab (wPCbTP), with the option of splitting the pertuzumab loading dose. After 12 weeks, responding patients continued wPCbTP for another 6 weeks, while non-responders switched to AC. Dose modifications and post-op therapy were at investigator discretion.
Results:
In 30 evaluable patients, the pCR rate was 77% (95% CI 58-90%); 12/14 (86%) in ER-negative and 11/16 (69%) in ER-positive. Only two patients transitioned to AC for non-response, of which one achieved pCR. There were no episodes of febrile neutropenia or grade >3 peripheral neuropathy, though several patients who continued wPCbTP stopped before week 18. Split-dose pertuzumab was associated with less grade >2 diarrhea (40%) than the standard loading dose (60%).
Conclusions:
pCR rates with our regimen were as high as reported with TCHP with fewer grade >3 toxicities, though diarrhea remains a concern. Too few patients had a suboptimal response to adequately test switching to AC. The wPCbTP regimen should be considered an alternative to TCHP as neoadjuvant therapy for HER2+BC.
ClinicalTrials.gov identifier: NCT02789657
Figure 1
Figure 2
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