The underlying premise of a recently initiated national clinical trial, is that following pathologic complete response to an abbreviated neoadjuvant regimen in human epidermal growth factor receptor 2 (HER2)-positive breast cancer, de-escalation of adjuvant therapy is potentially appropriate. However, the viability of de-escalation, as practically applied in the clinical setting considering the acceptability to patients and providers, has not been formally scrutinized and evaluated.
To determine the feasibility of de-escalated adjuvant therapy to trastuzumab plus pertuzumab only in patients with pathologic complete response following neoadjuvant paclitaxel + trastuzumab + pertuzumab, Adrienne G. Waks of the Dana-Farber Cancer Institute, Boston, MA, and colleagues conducted a single-arm pilot trial. Patients were deemed eligible for the study if they had a diagnosis of clinical anatomic stage II-III treatment-naïve HER2-positive breast cancer.
All participants received 12 doses of paclitaxel weekly, and 4 doses of trastuzumab plus pertuzumab every 3 weeks, and in cases of surgical delay, up to 6 doses were allowed. The primary objective was to assess adherence to protocol-specified antibody doublet therapy (trastuzumab plus pertuzumab only, without cytotoxic chemotherapy) in the adjuvant setting among participants with pathologic complete response following neoadjuvant paclitaxel + trastuzumab + pertuzumab. Trastuzumab emtansine was not considered cytotoxic chemotherapy. De-escalation would be deemed infeasible if the true rate of adherence to trastuzumab + pertuzumab only were less than 80% among participants with pathologic complete response to paclitaxel + trastuzumab + pertuzumab. Questionnaires were administered and records were examined to evaluate patients’ and physicians’ decision-making about adjuvant systemic therapy following pathologic complete response and nonpathologic complete response.
These participants were 99% female, with a median age of 50 years (range, 24-78 years). Eighty-six percent had stage II, 14% stage III tumors, and 32% were considered estrogen receptor–negative and progesterone receptor–negative. During neoadjuvant paclitaxel + trastuzumab + pertuzumab treatment, no patients’ cancer progressed. An incomplete clinical response following paclitaxel + trastuzumab + pertuzumab was experienced by 5 participants and were classified as nonpathologic complete response and were omitted from further analyses. At the time of analysis, 93 patients were evaluable for response to neoadjuvant therapy. Overall pathologic complete response rate was 55%; 10%, 28%. Of the 51 patients who had pathologic complete response to paclitaxel + trastuzumab + pertuzumab, 40 had verified data available regarding adjuvant chemotherapy receipt. Data for 39 of 40 patients (97.5%) who had pathologic complete response (did not receive adjuvant cytotoxic chemotherapy, met the trial’s prespecified primary end point thus declaring this a feasible approach), although data remain pending for 11 patients with pathologic complete response. Of the 30 patients who did not have a pathologic complete response to paclitaxel + trastuzumab + pertuzumab, approximately an equal number of patients received (14/30) and did not receive (16/30) adjuvant cytotoxic chemotherapy. For patients, the most commonly cited reasons for nonreceipt of adjuvant cytotoxic chemotherapy, despite residual disease at surgery, were having a plan for adjuvant trastuzumab emtansine alone (67% of patients), good response to preoperative chemotherapy (38% of patients), and plan for adjuvant hormonal therapy (24% of patients). Physicians’ most common reason cited for nonadministration of adjuvant chemotherapy, despite residual disease at surgery, was simply a plan for adjuvant trastuzumab emtansine reported by 81% of physicians. There were no breast cancer recurrences in the median 10.2 months of follow-up.
The investigators suggested that de-escalation of adjuvant cytotoxic chemotherapy among patients who experience pathologic complete response in stage II-III (early stage) HER2-positive breast cancer appears to be an acceptable approach for both patients and physicians. A significant number of patients with residual disease did not receive adjuvant cytotoxic chemotherapy, with the most common reason cited by patients and treating physicians being a plan for adjuvant trastuzumab emtansine. There were no breast cancer recurrences, with the brief follow-up.
In the ongoing national CompassHER2-pCR trial, the long-term efficacy of this approach will be determined more resolutely.
Source: Waks AG, Desai NV, Li T, et al. The DAPHNE trial: a feasibility study of chemotherapy de-escalation based on response to neoadjuvant paclitaxel-HP (THP) in HER2-positive breast cancer. Presented at: 2020 San Antonio Breast Cancer Symposium, December 8-11, 2020. Abstract PD3-05.