Abstract P2-16-19: Neoadjuvant weekly paclitaxel (wP) and carboplatin (Cb) with trastuzumab (T) and pertuzumab (P) in HER2-positive breast cancer (H+BC): A Brown University oncology group (BrUOG) study
Authors: Lopresti Mary Lorraine , Bian Jessica J. , Sakr Bachir J , Strenger Rochelle S , Legare Robert D. , Fenton Mary Anne , Witherby Sabrina M , Dizon Don S , Pandya Sonali V , Stuckey Ashley R , Edmondson David A , Gass Jennifer S , Emmick Christine M , Graves Theresa A , Cutitar Marlene , Olszewski Adam J , Sikov William M 
Published: March 2020

In H+BC, neoadjuvant chemotherapy (NACT) with dual HER2-targeted therapy achieves high pathologic complete response (pCR) rates, but the most common anthracycline-free regimen, every 3-week docetaxel and Cb with T and P (TCHP), causes significant hematologic and non-hematologic toxicities. We conducted a pilot study to assess the efficacy and toxicity of a weekly anthracycline-free regimen, and to assess whether patients (pts) with a suboptimal response to this regimen benefit from switching to doxorubicin/cyclophosphamide (AC).

Methods

Pts with clinical stage II-III H+BC receive wP 80 mg/m2 and Cb AUC 2 weekly with every 3-week T and P (wPCbTP). Investigators may split the week 1 loading dose of P (840 mg) into two weekly doses, and hold the 2nd dose for early onset toxicity, particularly diarrhea. Pts are restaged after 12 weeks with ultrasound or MRI. Responding pts receive another 6 weeks of wPCbTP, while nonresponders are switched to AC x 4, followed by surgery. Study participation is complete after a 3-month post-op visit. Dose modifications and post-op therapy are at investigator discretion.

Results

Enrollment (30 pts) is complete. Pathologic findings are available for 23 pts; the other 7 are due to undergo surgery by 10/2019. No pts have required switching to AC for suboptimal response at week 12; 2 have been switched for toxicity (1 each for diarrhea and recurrent cytopenias). pCR (T0/isN0) rates are tabulated below:

Pt grouppCR% (95% CI)All18/2378 (56-92) %ER(-)10/1191 (59-100) %ER(+)8/1267 (35-90) %Operable (Stage IIA-IIIA)14/1782 (57-96) %Inoperable (Stage IIIB-C)4/667 (22-96) %

In 23 pts, grade 3/4 toxicities observed include neutropenia (10/2, but no febrile neutropenia), anemia (3/0), thrombocytopenia (1/0), diarrhea (4/1), and 5 cases of grade 2 (but no grade ≥3) peripheral neuropathy. One pt each has required hospitalization for recurrent urinary tract, port site or breast infections while not neutropenic. wP has been dose-reduced for neuropathy after week 12 in 8 pts. Two pts discontinued Cb after hypersensitivity reactions in week 10. Treatment was discontinued during weeks 12-18 in 8 pts. P was held during weeks 1-6 for diarrhea in 5 pts and discontinued before week 12 in 3 pts; splitting the loading dose of P has not substantially reduced the incidence or severity of diarrhea.

Conclusions

Treatment with wPCbTP is associated with a high pCR rate (78%), comparable to those reported with TCHP in multicenter phase II-III trials, and is generally well tolerated, with fewer grade ≥3 toxicities, though diarrhea remains a concern. In some pts, cumulative toxicities make it difficult to continue treatment beyond week 12. Thus far, we have failed to identify a subset of pts in whom to test the efficacy of switching to AC after a suboptimal response to wPCbTP. This regimen appears to be worth exploring further, though we might consider switching to a less toxic regimen, or taking pts with an excellent response to surgery, after week 12. Supported by LifeCycle and the Lura Cook Hull Trust

Citation Format: Mary Lorraine Lopresti, Jessica J. Bian, Bachir J Sakr, Rochelle S Strenger, Robert D. Legare, Mary Anne Fenton, Sabrina M Witherby, Don S Dizon, Sonali V Pandya, Ashley R Stuckey, David A Edmondson, Jennifer S Gass, Christine M Emmick, Theresa A Graves, Marlene Cutitar, Adam J Olszewski, William M Sikov. Neoadjuvant weekly paclitaxel (wP) and carboplatin (Cb) with trastuzumab (T) and pertuzumab (P) in HER2-positive breast cancer (H+BC): A Brown University oncology group (BrUOG) study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-16-19.