Patients with HER2-positive, early breast cancer who respond to 2 cycles of neoadjuvant pertuzumab plus trastuzumab may benefit from continuing with a chemotherapy-free regimen, according to initial results of the phase 2 pherGAIN trial published in The Lancet Oncology.

The study authors noted that neoadjuvant dual blockade of HER2 results in pathologic complete response (pCR) rates of up to 36.3%, which provides rationale for chemotherapy de-escalation strategies. The present study was designed to evaluate the use of metabolic response to neoadjuvant dual blockade for chemotherapy de-escalation among patients with HER2-positive, early breast cancer.

The open-label, phase 2 pherGAIN trial ( Identifier: NCT03161353) included 71 patients randomly assigned to receive docetaxel plus carboplatin, trastuzumab, and pertuzumab and 285 patients randomly assigned to receive dual HER2 blockade alone with pertuzumab plus trastuzumab. Letrozole or tamoxifen were added to the dual blockade group if patients had hormone receptor–positive disease.

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After 2 cycles of treatment, ¹⁸F-FDG-PET was performed. All patients who received chemotherapy plus HER2 blockade continued their regimen regardless of the results.

Patients receiving dual blockade without chemotherapy continued with the same regimen if they had achieved a response. Patients who did not respond were switched to 6 cycles of chemotherapy plus dual HER2 blockade.

All patients underwent surgery 2 to 6 weeks after their final neoadjuvant dose and continued with adjuvant pertuzumab plus trastuzumab.

Overall, 81% of patients responded to treatment, and 93% proceeded to surgery, including 89% of patients who received chemotherapy plus HER2 blockade and 94% of patients in the HER2 blockade-only arm.

The study’s coprimary endpoints are the proportion of responders with pCR in the dual blockade group and 3-year invasive disease-free survival.

The pCR endpoint was met, with 37.9% of ¹⁸F-FDG-PET responders to dual HER2 blockade achieving pCR compared with 25.9% of ¹⁸F-FDG-PET nonresponders (P =.068).

The pCR rate was 57.7% in the chemotherapy-HER2 blockade group and 35.4% in the dual HER2 blockade-only group (P <.0001).

Drug-related serious adverse events (AEs) occurred in 28% of patients who received chemotherapy plus HER2 blockade and 4% of patients who received only HER2 blockade. AEs led to treatment discontinuation in 4% of the chemotherapy arm and less than 1% of the non-chemotherapy arm. 

“Depending on the forthcoming results for the 3-year invasive disease-free survival endpoint, this strategy might be a valid approach to select patients not requiring chemotherapy,” the study authors concluded.

Disclosures: This research was supported by F Hoffmann-La Roche. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Pérez-García JM, Gebhart G, Borrego MR, et al. Chemotherapy de-escalation using an ¹⁸F-FDG-PET-based pathological response-adapted strategy in patients with HER2-positive early breast cancer (PHERGain): a multicentre, randomised, open-label, non-comparative, phase 2 trial. Lancet Oncol. Published online May 18, 2021. doi:10.1016/S1470-2045(21)00122-4