Targeted Treatment of HER2-Positive Breast Tumors – Updates from ESMO 2020 Congress

Dual Anti-HER2 Blockade in Combination with Chemotherapy

Based on the results of the CLEOPATRA clinical trial, the combination therapy of trastuzumab, pertuzumab, and docetaxel is used as a standard 1st line treatment in patients with HER2⁺ locally advanced or metastatic breast tumor. The single-arm clinical trial PERUSE evaluated the efficacy and safety of the combination of trastuzumab and pertuzumab with a taxane of the treating physician's choice. The final results of this study were presented at the congress. Patients with inoperable HER2⁺ locally advanced or metastatic disease received dual anti-HER2 therapy with docetaxel (54%), paclitaxel (41%), or nab-paclitaxel (5%) until disease progression or unacceptable toxicity.

PERUSE Study Results

A total of 1,436 patients with a median age of 54 years were treated, with a median follow-up time of 69 months. The observed safety profile and treatment efficacy were consistent with the conclusions of the CLEOPATRA study. The median progression-free survival (PFS) for the entire cohort of patients reached 20.7 months (95% confidence interval [CI] 18.9−23.1), and the median overall survival (OS) was 65.3 months (95% CI 60.9−70.9). The median PFS for the docetaxel-treated subgroup was 19.4 months (95% CI 16.9−22.1), patients treated with paclitaxel achieved a PFS of 23.2 months (95% CI 19.6−22.1), and in the nab-paclitaxel group, it was 19.2 months (95% CI 11.7−37.1).

Grade ≥ 3 adverse events were observed in 61% of patients, most commonly neutropenia or diarrhea. Due to adverse events, it was necessary to discontinue pertuzumab therapy in 10% of patients, trastuzumab in 9%, and chemotherapy in 20% of patients.

From Clinical Trials to Real-World Practice

An observational study conducted in 18 Italian hospitals utilized data from all 347 patients treated with the trastuzumab/pertuzumab/taxane combination since pertuzumab entered the market. The chosen taxane was docetaxel in 60% of cases and paclitaxel in 40%. The achieved objective response rate (ORR) to treatment was 77% with a median PFS of 26.9 months (95% CI 20-33.8). The safety profile was in line with available data.

Conclusion

The final results of the PERUSE study and data from real-world clinical practice support the use of the trastuzumab + pertuzumab + taxane combination in the 1st line treatment of locally advanced or metastatic HER2⁺ breast cancer. Paclitaxel appears to be a valid alternative to docetaxel treatment.

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Sources:
1. Miles D. W., Ciruelos E. M., Schneeweiss A. et al. Final results from PERUSE, a global study of pertuzumab (P), trastuzumab (H) and investigator’s chosen taxane as first-line therapy for HER2-positive locally recurrent/metastatic breast cancer (LR/mBC). Ann Oncol 2020; 31 (suppl_4): S348−S395, doi: 10.1016/annonc/annonc268. Available at: https://oncologypro.esmo.org/meeting-resources/esmo-virtual-congress-2020/final-results-from-peruse-a-global-study-of-pertuzumab-p-trastuzumab-h-and-investigator-s-chosen-taxane-as-first-line-therapy-for-her2-positi
2. Garrone O., Giarratano T., Michelotti A. et al. From the CLEOPATRA study to real life: Final results from the G.O.N.O. SUPER trial. Ann Oncol 2020; 31 (suppl_4): S348−S395, doi: 10.1016/annonc/annonc268. Available at: https://oncologypro.esmo.org/meeting-resources/esmo-virtual-congress-2020/from-the-cleopatra-study-to-real-life-final-results-from-the-g.o.n.o.-super-trial