N. Engl. J. Med.
Pembrolizumab for Early Triple-Negative Breast Cancer.
Abstract
Background
Previous trials showed promising antitumor activity and an acceptable safety profile associated with pembrolizumab in patients with early triple-negative breast cancer. Whether the addition of pembrolizumab to neoadjuvant chemotherapy would significantly increase the percentage of patients with early triple-negative breast cancer who have a pathological complete response (defined as no invasive cancer in the breast and negative nodes) at definitive surgery is unclear.
Methods
In this phase 3 trial, we randomly assigned (in a 2:1 ratio) patients with previously untreated stage II or stage III triple-negative breast cancer to receive neoadjuvant therapy with four cycles of pembrolizumab (at a dose of 200 mg) every 3 weeks plus paclitaxel and carboplatin (784 patients; the pembrolizumab-chemotherapy group) or placebo every 3 weeks plus paclitaxel and carboplatin (390 patients; the placebo-chemotherapy group); the two groups then received an additional four cycles of pembrolizumab or placebo, and both groups received doxorubicin-cyclophosphamide or epirubicin-cyclophosphamide. After definitive surgery, the patients received adjuvant pembrolizumab or placebo every 3 weeks for up to nine cycles. The primary end points were a pathological complete response at the time of definitive surgery and event-free survival in the intention-to-treat population.
Results
At the first interim analysis, among the first 602 patients who underwent randomization, the percentage of patients with a pathological complete response was 64.8% (95% confidence interval [CI], 59.9 to 69.5) in the pembrolizumab-chemotherapy group and 51.2% (95% CI, 44.1 to 58.3) in the placebo-chemotherapy group (estimated treatment difference, 13.6 percentage points; 95% CI, 5.4 to 21.8; P<0.001). After a median follow-up of 15.5 months (range, 2.7 to 25.0), 58 of 784 patients (7.4%) in the pembrolizumab-chemotherapy group and 46 of 390 patients (11.8%) in the placebo-chemotherapy group had disease progression that precluded definitive surgery, had local or distant recurrence or a second primary tumor, or died from any cause (hazard ratio, 0.63; 95% CI, 0.43 to 0.93). Across all treatment phases, the incidence of treatment-related adverse events of grade 3 or higher was 78.0% in the pembrolizumab-chemotherapy group and 73.0% in the placebo-chemotherapy group, including death in 0.4% (3 patients) and 0.3% (1 patient), respectively.
Conclusions
Among patients with early triple-negative breast cancer, the percentage with a pathological complete response was significantly higher among those who received pembrolizumab plus neoadjuvant chemotherapy than among those who received placebo plus neoadjuvant chemotherapy. (Funded by Merck Sharp & Dohme [a subsidiary of Merck]; KEYNOTE-522 ClinicalTrials.gov number, NCT03036488.).
Related Questions
In a patient with PDL1+ TNBC who has had an excellent response to sacituzumab govitecan + pembrolizumab, would you ever stop the SG and continue the pembro alone?
In ASCENT-04, patients received treatment until disease progression, unacceptable toxicity, withdrawal of consent, or death. Pembrolizumab was administered for a maximum of 35 cycles, which is approximately two years. The strategy of discontinuing SG and continuing pembrolizumab as maintenance thera...
How do you select first-line therapy for PD-L1-positive metastatic TNBC?
At this point, we only have mature data on pembro and SG, and this is the regimen I would use.
Is there evidence supporting the use of nab-paclitaxel in place of paclitaxel in the KEYNOTE-522 neoadjuvant regimen for triple-negative breast cancer, in cases of paclitaxel hypersensitivity?
While I am not aware of any evidence on the specific substitution of nab-paclitaxel for paclitaxel in the KEYNOTE-522 regimen, there is certainly data on the efficacy of nab-paclitaxel in the neoadjuvant setting in a variety of breast cancer subtypes, For example, in the ETNA trial (Gianni et al., P...
What neoadjuvant chemotherapy do you suggest for a rapidly growing triple-negative breast cancer?
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What are your top takeaways in Medical Oncology from SABCS 2024?
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When do you consider the addition of concurrent pembrolizumab to breast irradiation?
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What would be your treatment approach in a premenopausal BRCA2+ patient with cT2N0 grade 2-3, ER negative, PR variably positive (30%; staining weak to high), HER2 negative breast cancer?
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How do you treat a patient with TNBC, BRCA WT, who received KEYNOTE-522 with residual disease post neoadjuvant therapy?
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What systemic therapy would you recommend for axillary recurrence of triple negative secretory breast cancer previously treated with mastectomy alone?
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How do you approach breast RT in a patient with a recent history of ipsilateral thoracic irradiation?
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How would you manage a patient who develops acute stroke during neoadjuvant chemotherapy with KEYNOTE-522 for Stage III triple negative breast cancer?
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How would you manage a left sided triple negative breast cancer with a concurrent left sided locally advanced non-small cell lung cancer?
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Would you consider chemoimmunotherapy (CP-Pembro-AC) in triple negative breast cancer if tumor is not palpable on physical exam?
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What is your approach in treatment of oligometastatic triple negative inflammatory breast cancer?
There isn't one answer partly because "oligometastatic" isn't well-defined or uniform across cases. Given the rarity of inflammatory breast cancer, we don't have a lot of prospective data to guide treatment decisions either. Some have used 5 or fewer lesions as a definition for oligometastatic disea...
How would you treat a patient with TNBC with a residual strongly PR+, ER- breast mass on mastectomy after neoadjuvant KEYNOTE 522 based chemoimmunotherapy?
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Can you safely proceed with breast irradiation during treatment with immunotherapy?
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