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Randomized Controlled Trial
. 2023 Jun;199(2):243-252.
doi: 10.1007/s10549-023-06881-8. Epub 2023 Mar 22.

Long-term outcomes of dual vs single HER2-directed neoadjuvant therapy in NSABP B-41

Priya Rastogi  1   2   3 , Gong Tang  4 , Saima Hassan  5   6 , Charles E Geyer Jr  5   7 , Catherine A Azar  5   8 , Gustav C Magrinat  5   9 , J Marie Suga  5   10 , Harry D Bear  5   11 , Luis Baez-Diaz  5   12 , Shakir Sarwar  5   13 , Jean-Francois Boileau  5   14 , Adam M Brufsky  5   7 , Henry R Shibata  5   15 , Hanna Bandos  4 , Soonmyung Paik  5   16 , Greg Yothers  4 , Sandra M Swain  5   17 , Eleftherios P Mamounas  5   18 , Norman Wolmark  5   7
Affiliations
Randomized Controlled Trial

Long-term outcomes of dual vs single HER2-directed neoadjuvant therapy in NSABP B-41

Priya Rastogi et al. Breast Cancer Res Treat. 2023 Jun.

Abstract

Background: The primary aim of this randomized neoadjuvant trial in operable, HER2-positive breast cancer, was to determine the efficacy on pathologic complete response (pCR) of substituting lapatinib (L) for trastuzumab (T) or adding L to T, in combination with weekly paclitaxel (WP) following AC. Results on pCR were previously reported. Here, we report data on planned secondary endpoints, recurrence-free interval (RFI) post-surgery, and overall survival (OS).

Methods: All patients received standard AC q3 weeks × 4 cycles followed by WP (80 mg/m2) on days 1, 8, and 15, q28 days × 4 cycles. Concurrently with WP, patients received either T (4 mg/kg load, then 2 mg/kg) weekly until surgery, L (1250 mg) daily until surgery, or weekly T plus L (750 mg) daily until surgery. Following surgery, all patients received T to complete 52 weeks of HER2-targeted therapy. 522 of 529 randomized patients had follow-up. Median follow-up was 5.1 years.

Results: RFI at 4.5 years was 87.2%, 79.4% (p = 0.34; HR = 1.37; 95% CI 0.80, 2.34), and 89.4% (p = 0.37; HR = 0.70; 0.37, 1.32) for arms T, L, and TL, respectively. The corresponding five-year OS was 94.8%, 89.1% (p = 0.34; HR = 1.46; 0.68, 3.11), and 95.8% (p = 0.25; HR = 0.58; 0.22, 1.51), respectively. Patients with pCR had a much better prognosis, especially in the ER-negative cohort: RFI (HR = 0.23, p < 0.001) and OS (HR = 0.28, p < 0.001).

Conclusions: Although pCR, RFI, and OS were numerically better with the dual combination and less with L, the differences were not statistically significant. However, achievement of pCR again correlated with improved outcomes, especially remarkable in the ER-negative subset.

Clinical trials registration: NCT00486668.

Keywords: HER2-positive breast cancer; HER2-targeted therapy; Lapatinib; Neoadjuvant chemotherapy; Trastuzumab.

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Conflict of interest statement

SH: Research funding for unrelated projects from Pfizer and Exact Sciences; Honorary Fees from Exact Sciences and Merck for Advisory Board meetings. CEG, Jr: Abbvie: Contracted Research (Terminated, Jul 1, 2022), Writing assistance (Terminated, Jul 1, 2022); AstraZeneca: Contracted Research (Ongoing), Writing assistance (Ongoing); Daiichi/Sankyo: Contracted Research (Ongoing); Exact Sciences: Consulting Fees (e.g., advisory boards) (Ongoing); F. Hoffman-La Roche Ltd: Contracted Research (Ongoing); Genentech: Contracted Research (Ongoing), Writing assistance (Ongoing) HDB: Non-relevant disclosures: Talks/honoraria, Genentech. J-FB: Honoraria/speaker’s fee: Roche, Exact Sciences, Merck, AstraZeneca; Advisory boards or speakers’ bureaus: Pfizer, Novartis, Merck. AstraZeneca, Lilly, Roche; Funded grants or clinical trials: Institutional PI, clinical trial: Roche, Merck, Lilly, Novartis, Pfizer, Bristol Myers Squibb, AstraZeneca (also Steering Committee). AMB: Consultant for Astra-Zeneca, Roche, Puma, Seattle Genetics, Macrogenics, Daiichi Sankyo. SMS: Grants/contracts: Genentech/Roche, Kailos Genetics, BCRF; Consulting fees: Roche/Genentech, Molecular Therapeutics; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events: Genentech/Roche, Daiichi Sankyo; Support for attending meetings and/or travel: Genentech/Roche travel to Boston 11/2019; Participation on a Data Safety Monitoring Board or Advisory Board: DSMB AstraZeneca; Ad Board: AstraZeneca, Daiichi Sankyo, Exact Sciences, Biotheranostics, Natera, Merck, Silverback Therapeutics, Athenex, Lilly; Scientific Advisory Board: Inivata. Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid: NSABP Vice chairman; CCF, ASCO Director; Receipt of equipment, materials, drugs, medical writing, gifts or other services: Third-party writing: Genentech/Roche and AstraZeneca. EPM: Genentech/Roche, Exact Sciences, Merck: Consultant, Speaker’s Bureau; Biotheranostics, Puma Biotechnology, Agendia, AstraZeneca: Consultant. All other authors have no other potential COIs to report.

Declarations

Conflict of interest The authors had full access to all the data and had final responsibility for the decision to submit for publication.

Figures

Fig. 1
Fig. 1
Kaplan–Meier estimates of recurrence-free interval by treatment arms: NSABP B-41. a Overall, b Among hormone receptor-positive patients, c Among hormone receptor-negative patients
Fig. 2
Fig. 2
Kaplan–Meier estimates by treatment arms: NSABP-B-41. a Overall survival, b Event-free survival
Fig. 3
Fig. 3
Kaplan-Meier estimates by pCR status: NSABP B-41. a Recurrence-free interval, b Overall survival, c Event-free survival
See this image and copyright information in PMC

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