Neoadjuvant Anthracycline-Free Regimen Achieves pCR With Less Toxicity in HER2+ Breast Cancer


Pertuzumab (Perjeta), trastuzumab (Herceptin), and nab-paclitaxel used as neoadjuvant therapy (NT) in patients with HER2-positive locally advanced breast cancer showed comparable pathologic complete response (pCR) with docetaxel, carboplatin, trastuzumab, and pertuzumab (TCHP) with less toxicities, according to data presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting.

“This anthracycline-free regimen which included nab[-paclitaxel] achieved great pCR rate of 64.4% in patients [with HER2-positive breast cancer] with fewer treatment-related toxicities,” the investigators wrote in about their findings. “The pCR rate is comparable with [TCHP] therapy in NT setting, but without the treatment-associated toxicities. This suggests we may be able to safely avoid anthracyclines and carboplatin for NT in [these] patients.”

There were 45 patients with biopsy-confirmed HER2-positive locally advanced breast cancer or inflammatory breast cancer enrolled in this phase 2, prospective, open-label trial (NCT01730833). All patients were treated with 6 cycles of NT: pertuzumab given at 840 mg as the loading dose, then 420 mg intravenously on day 1 every 21 days; trastuzumab given at 4 mg/kg loading dose, then 2 mg/kg weekly; and nab-paclitaxel given intravenously at 100 mg/m2 weekly. Patients were evaluated every 3 months for 4 years, then every 6 months the fifth year, and per standard of care every year after.

After a median follow-up of 50 months (95% CI, 32.3-55.6), the median treatment cycles completed was 6, although 4 patients had 1 or more cycles delayed and 32 had 1 or more cycles modified. Out of the 45 patients, 29 (64%) achieved pCR. The 5-year disease-free survival (DFS) rate for these patients was 96.3% (95% CI, 76.5%-99.5%) and the overall survival (OS) rate at 5 years was 94.1% (95% CI, 65.0%-99.1%).

In the 16 patients (36%) without pCR, the 5-year DFS rate was 74.3% (95% CI, 39.1%-91.0%). The 5-year OS rate in those without pCR was 93.3% (95% CI, 61.3%-99.0%). The OS rate at 5 years in the overall population was 94.1% (95% CI, 77.6%-98.5%).

Of the 29 patients who were estrogen and progestogen receptor (ER/PR) negative, 15 (52%) achieved pCR. Fourteen of the 29 ER/PR–positive patients (48%) achieved pCR.

Although pCR may predict improved DFS and OS, that was not the case in this trial. The improved pCR did not translate to DFS benefit according to the investigators.

This phase 2 trial was comparing the anthracycline-free regimen to the NeoSphere trial (NCT00545688) of neoadjuvant pertuzumab and trastuzumab in patients with HER2-positive breast cancer. In NeoSphere, the pCR rate was 39.3%, which needed to be matched or surpassed for this study to be successful. Since the exact method point estimate for the pCR rate was 64.4% (95% CI, 0.49-0.78; P < .001), this ruled out the NeoSphere response rate.

The most common grade 3 treatment-related adverse events (TRAEs) in 2 or more patients included hypertension at 16%, anemia at 9%, and diarrhea, alanine aminotransferase, fatigue, and rash all at 4%. There was 1 instance of grade 4 toxicity with dyspnea. The most common grade 2 TRAEs were anemia at 24% and hypertension and fatigue both at 22%. Three patients (7%) needed granulocyte colony stimulating factor support for neutropenia.

At initial evaluation, there were 20 patients with ER/PR­–negative disease and 25 with ER/PR–positive disease. None of the patients had prior radiation therapy. The most common tumor stage at baseline was stage II in 67% of patients, then stage III in 31%, and stage I in 2%. All of the patients had infiltrating ductal carcinoma. There were 24 post-menopausal patients (53%), 18 pre-menopausal (40%), 2 peri-menopausal (4%), and 1 patient (2%) with menopausal status not applicable.

The median age on this trial was 56 years (range, 31-78). The majority of patients were Hispanic (42%) or non-Hispanic white (38%). Sixteen percent of patients were Asian, 2% were African American, and 2% had unknown race or ethnicity. Most patients had an ECOG performance status of 0 (62%) and the rest had a performance status of 1 (38%).


Lavasani SM, Yost SE, Frankel PH, et al. Phase II prospective open label study of neoadjuvant pertuzumab, trastuzumab, and nab-paclitaxel in patients with HER-2 positive advanced breast cancer. J Clin Oncol. 2021;39(suppl 15):583. doi:10.1200/JCO.2021.39.15_suppl.583

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