Although carboplatin can certainly improve pCR rates, confirmatory studies to evaluate its effect on EFS have yet to be reported. As we consider the results, it is important to note that the neoadjuvant chemotherapy backbone used was not a standard regimen and that adjuvant capecitabine was not allowed. 6 After surgery, all patients received 9 cycles of pembrolizumab irrespective of pCR result. The KEYNOTE-522 study was a registration phase III study evaluating the combination of weekly paclitaxel 1 + carboplatin (AUC1.5 weekly or AUC 5 every 3 weeks) followed by AC every 3 weeks, with or without pembrolizumab in a 2:1 randomization. A pooled analysis demonstrated that the addition of carboplatin improved pCR rates resulting in the incorporation of carboplatin in the subsequent registration study, KEYNOTE-522. The arms that were eventually incorporated into the registration KEYNOTE-522 study (solvent-based paclitaxel was the taxane used) had pCR rates of 25% (carboplatin area under the curve of 2 ) and 50% (carboplatin AUC5) in KEYNOTE-173.

Arms that included nab-paclitaxel with carboplatin had the highest pCR rates (60%–80%). The non–carboplatin-containing arm (the taxane used was nab-paclitaxel) was associated with a pCR rate of 55%. KEYNOTE-173 was a noncomparative multicohort phase I study of pembrolizumab added to various neoadjuvant anthracycline and taxane-based regimens in TNBC. Paclitaxel weekly ×12 Doxorubicin/Cyclophosphamide q2wk ×4 cycles Nab-paclitaxel (weekly) ×12 wk Epirubicin/Cyclophosphamide q2wk ×4 cycles Paclitaxel (weekly)/carboplatin (AUC5 q3wk) q3wk ×4 cycles Nab-paclitaxel (weekly)/carboplatin AUC2 weekly ×2 q3wk, ×8 cycles Nab-paclitaxel (weekly) ×12 wk Doxorubicin/Cyclophosphamide q2wk ×4 cycles Paclitaxel (weekly)/carboplatin (AUC1.5 weekly or AUC5 q3wk) q3wk ×4 cycles Doxorubicin/Cyclophosphamide q3wk ×4 cycles 3, 6, 10– 13 One such study, GeparNUEVO, which evaluated the addition of durvalumab to anthracycline and taxane-based neoadjuvant chemotherapy (with no adjuvant durvalumab prescribed), did not demonstrate a statistically significant improvement in pCR, but did show a clinically and statistically significant improvement in EFS in a planned secondary analysis. A number of studies have been reported since then, with some, but not all, showing improvements in pCR in the ICI-containing arms ( Table 1). 10 In this study, pembrolizumab was added only to weekly paclitaxel, and all patients received dose-dense (every 2 weeks) doxorubicin and cyclophosphamide (AC). The first study to demonstrate potential benefit of the addition of a PD-1 inhibitor to neoadjuvant chemotherapy was the iSPY2 study, in which the pCR rate almost tripled from 22% to 60%. Immune checkpoint inhibitors (ICIs) and specifically PD-1 and PD-L1 inhibitors, have revolutionized cancer care across multiple cancer histologies, and have recently had their first regular approvals in TNBC. This brief report deciphers the available data to provide clinicians guidance to optimize systemic recommendations for patients with early-stage TNBC.Įxperience With Neoadjuvant Chemoimmunotherapy 3, 6 The new approval of the PD-1 inhibitor pembrolizumab in combination with chemotherapy in high-risk early-stage TNBC has brought into question several practical considerations.

7– 9 Recent studies in patients with TNBC that included neoadjuvant chemoimmunotherapy combinations have shown clinically significant improvement in EFS despite no or modest improvements in pCR. 4– 6 Although an improvement in pCR in a registration study can lead to accelerated approval by the FDA, an event-free survival (EFS) benefit must still be demonstrated. 1– 3 For patients who achieve pCR, prognosis is excellent, with recurrence rates typically, ˂10% however, for those who do not achieve a pCR, recurrence rates can approach 50%. Patients with TNBC often present with stage II or III disease and receive neoadjuvant therapy, historically comprising of anthracycline- and taxane-based chemotherapy, which can produce pathologic complete response (pCR) rates of approximately 40%. Although TNBC is a heterogeneous group of breast cancers of distinct phenotypes, there are limited biomarkers to guide distinct treatment of early-stage disease. Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that lacks expression of the estrogen and progesterone receptors (ER and PR, respectively) and expression or amplification of HER2/neu.

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