Preliminary safety and efficacy results of pertuzumab in combination with trastuzumab and taxane therapy in patients with HER2-positive metastatic breast cancer in the PERUSE study

Preliminary data of the worldwide, single-arm phase IIIb PERUSE study showed that the safety and efficacy of first-line pertuzumab in combination with trastuzumab and a taxane of investigator’s choice for HER2-positive metastatic breast cancer are in agreement with the results of the phase III CLEOPATRA study.¹ Although the data are premature, the median progression-free survival (PFS) for all combinations was 21.2 months. Across the three groups, median PFS in the docetaxel group was 19.7 months, in the paclitaxel group 24.7 months, and in the nab-paclitaxel group 18.1 months. Compared to pertuzumab+trastuzumab plus docetaxel, the combination of pertuzumab+trastuzumab plus paclitaxel or nab-paclitaxel led to numerically fewer febrile neutropenia events. The incidence of peripheral neuropathy was numerically higher in patients who received pertuzumab, trastuzumab plus paclitaxel compared to patients who received the combination plus docetaxel or nab-paclitaxel.

In the randomised phase III CLEOPATRA study, the combination of pertuzumab, trastuzumab and docetaxel significantly improved progression-free survival (PFS) and overall survival (OS) in patients with HER2-positive metastatic breast cancer (MBC).^2,3 Based on these findings, the combination has been approved as first-line therapy for HER2-positive MBC. PERUSE is an ongoing, open-label, single-arm, multicentre, phase IIIb study designed to assess the safety and efficacy of first-line pertuzumab in combination with trastuzumab and the investigator’s choice of taxane in patients with HER2-positive locally recurrent (LR) or MBC.

The safety/intent-to-treat (ITT) population of the PERUSE study includes 1,436 patients at data cut-off (April 1^st, 2016), of whom all received pertuzumab, and 1,429 patients received a taxane. The initial taxane selected by the investigator was docetaxel (N=775), paclitaxel (N=589), and nab-paclitaxel (N=65). Patients could cross over between taxanes during the study. The median age was 54 years. Overall, 64% of patients had hormone receptor-positive disease, and 75% had visceral disease at screening. The median treatment duration was 16.1 months for pertuzumab and 16.0 months for trastuzumab. The median duration of treatment with docetaxel, paclitaxel, or nab-paclitaxel was 3.8, 4.2, and 3.9 months, respectively. Most patients discontinued treatment because of disease progression (pertuzumab 45.8%; trastuzumab 46.2%; taxane 15.1%), adverse events (pertuzumab 8.1%; trastuzumab 7.3%; taxane 15.7%), or other reasons (pertuzumab 4.2%; trastuzumab 4.5%; taxane 24.5%).

After a median follow-up of 17.2 months, the most common treatment related adverse events (TEAEs) of any grade were diarrhoea (67.1%), alopecia (47.5), nausea (33.7%), fatigue (30.7%), and asthenia (28.3%). Serious TEAEs were reported in 34.2% of the total safety population, including 36.4% of patients who received docetaxel, 31.4% who received paclitaxel, and 32.2% who received nab-paclitaxel. The overall incidence of grade ≥3 TEAEs in the PERUSE study was generally similar or lower than observed in the pertuzumab arm of the CLEOPATRA study.

Of the grade ≥3 TEAEs selected on the basis of the most common grade ≥3 AEs observed in the CLEOPATRA study was neutropenia more common among patients who received docetaxel (14.2%) compared to those who received paclitaxel (5.3%) or nab-paclitaxel (1.5%). The incidence of febrile neutropenia was 10.5% in the docetaxel group, 1.2% in the paclitaxel group, and 0% in the nab-paclitaxel group. The incidence of peripheral neuropathy, on the other hand, was more common in the paclitaxel group (2.5%) compared to the docetaxel (1.3%), and nab-paclitaxel group (0%). Fatigue and diarrhoea were comparable between the treatment arms. Additionally, left ventricular dysfunction rates observed in the PERUSE study were low and in line with left ventricular dysfunction rates in the pertuzumab arm of the CLEOPATRA study (0.8% versus 1.2%, respectively).^1,2 Preliminary PFS findings for all combinations were consistent with those seen in the CLEOPATRA study of pertuzumab+trastuzumab+docetaxel. Median PFS in the ITT population was 21.2 months, with a median PFS of 19.7 months, 24.7 months, and 18.1 months in the docetaxel, paclitaxel, and nab-paclitaxel group, respectively.

In conclusion, the combination of pertuzumab plus trastuzumab plus a taxane of investigator’s choice in the PERUSE study had an efficacy and safety that was comparable to the efficacy and safety findings of pertuzumab in combination with trastuzumab and docetaxel in the CLEOPATRA study. The PERUSE study is still ongoing and the presented analysis is only preliminary. The final analysis will be expected in 2020.

References

1. Bachelot T, Puglisi F, Ciruelos E, et al. Preliminary safety and efficacy of first-line pertuzumab combined with trastuzumab and taxane therapy for HER2-positive locally recurrent/metastatic breast cancer (PERUSE). San Antonio Breast Cancer Symposium 2016, abstract P4-21-04.
2. Baselga J, Cortés J, Kim SB, et al. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med 2012;366:109-19.
3. Swain SM, Baselga J, Kim SB, et al. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med 2015;372:724-34.