Neoadjuvant chemotherapy in combination with nab-paclitaxel and pembrolizumab shows promising pathological complete response rates.
Pembrolizumab (pembro) is the only approved immune checkpoint inhibitor for the neoadjuvant treatment of early triple-negative breast cancer (TNBC). It was introduced in combination with carboplatinum/paclitaxel and anthracycline/cyclophosphamide chemotherapy. Nab-paclitaxel (nP), although not approved, is also effective in TNBC.
A study in the European Journal of Cancer evaluated the efficacy and safety of nP-containing neoadjuvant chemotherapy combined with pembro in patients with TNBC.
Study Population
The study comprised 50 patients with untreated non-metastatic invasive TNBC. The mean patient age was 52.2 years. A total of 39 participants completed the predefined requirement for a per-protocol treatment.
High Complete Response Rate Obtained With Neoadjuvant Chemotherapy Plus nP and Pembro
The primary endpoint was pathological complete response (pCR) with no invasive tumor residuals in the breast or axillary lymph nodes (ypT0/is ypN0). A total of 33 (66%; p=0.02) patients achieved the primary endpoint. Hence, neoadjuvant pembro plus nP followed by epirubicin/cyclophosphamide led to a reasonably high pCR rate of 66%. Out of 39 patients who completed the per-protocol treatment, 28 (71.8%) were reported to have pCR.
Pembro Boost’s Impact on Response Rates and Pd-L1 Expression
Patients who received a pre-chemotherapy single dose of pembro showed a pCR rate of 59.6%, while the patients without the pembro boost showed a pCR rate of 73.9%. Respective pCR rates in the per-protocol population were 65.3% and 81.3%. Out of 46 patients, 32 demonstrated a partial or complete response 6 weeks after starting nP. Clinical response after 6 weeks correlated well with the later achievement of pCR. PD-L1 expression combined positive score (CPS) was assessed in 46 tumor blocks. The pCR rates (ypT0/is ypN0) with a CPS of 0, ≥1, ≥10, and ≥20 were 42.9%, 69.2%, 68.2%, and 80%, respectively.
No New Immune-Related Adverse Events Observed
The relative dose intensity (ratio of administered doses to planned doses) was 89.4% for pembro, 92.6% for nP, 91.1% for epirubicin, and 91.4% for cyclophosphamide in the safety population. All the patients had at least one adverse event (AE), and 64.2% had at least one grade 3/4 AE.
The most common AEs were fatigue, peripheral sensory neuropathy, neutropenia, nausea, and skin reactions. The most common grade 3/4 AEs were neutropenia, fever, and other blood and lymphatic disorders. AEs of special interest were in the expected ranges, with no new safety signals.
Decreased Quality of Life Noted Under Therapy
Quality of life assessment through the EORTC-QLQ-C30 questionnaire showed a drop in the general health scores from 70–75 at the start of therapy to 50–60 by the time of surgery.
Source
Fasching, P. A., Hein, A., Kolberg, H., Häberle, L., Uhrig, S., Rübner, M., Belleville, E., Hack, C. C., Fehm, T., Janni, W., Hartmann, A., Erber, R., Theuser, A., Brucker, S. Y., Hartkopf, A. D., & Untch, M. (2023). Pembrolizumab in combination with nab-paclitaxel for the treatment of patients with early-stage triple-negative breast cancer – A single-arm phase II trial (NeoImmunoboost, AGO-B-041). European Journal of Cancer, 184, 1–9. https://doi.org/10.1016/j.ejca.2023.01.001
