Different Taxanes, Similar Outcomes in Advanced HER2-Positive Breast Cancer

Final results from a routine-practice comparison of taxane agents showed that the drugs offered comparable safety and efficacy in advanced HER2-positive breast cancer.

Median progression-free survival (PFS) was about 21 months and median overall survival (OS) was 65 months with dual anti-HER2 therapy and was similar among patients who received paclitaxel or docetaxel, as well as a small number of patients treated with nab-paclitaxel (Abraxane). Safety and other endpoints were similar between treatment groups and consistent with those of the CLEOPATRA study, which compared trastuzumab plus pertuzumab (Perjeta) versus trastuzumab alone in addition to docetaxel.

The results provide reassurance that the dual anti-HER2 regimen is safe and effective when paired with a clinician’s choice of taxane, reported David Miles, MD, of Mount Vernon Cancer Centre in Northwood, England, and co-authors in Annals of Oncology.

“Final results from PERUSE complement the pivotal CLEOPATRA phase III trial results, demonstrating the generalizability of the findings to a routine clinical practice setting and the broader applicability of the results to alternative taxane backbones, particularly paclitaxel,” the authors wrote.

“These results add to the existing body of evidence and reinforce the role of dual HER2 blockade with pertuzumab and trastuzumab in combination with a taxane as the standard-of-care first-line regimen for HER2-positive locally relapsed or metastatic breast cancer,” they added.

The PERUSE trial addressed a question that lingered in the aftermath of CLEOPATRA, which demonstrated the superiority of dual anti-HER2 therapy plus docetaxel versus trastuzumab and docetaxel in advanced HER2-positive breast cancer: Could oncologists and their patients expect similar outcomes with a different taxane?

Investigators on six continents enrolled 1,436 patients with inoperable locally recurrent/metastatic HER2-positive breast cancer, all of whom received pertuzumab and trastuzumab. The choice of taxane was left to the treating physicians, and 588 patients initially received paclitaxel. Nab-paclitaxel was the taxane of choice in 65 cases, and the rest of the patients received docetaxel. The primary endpoint was safety, and PFS and OS were key secondary endpoints.

Grade ≥3 adverse events (AEs) occurred in 61% of patients and were attributed to pertuzumab in 20% of cases, trastuzumab in 17%, and the taxane in 36%. The most commonly reported events were neutropenia (10%) and diarrhea (8%). Consistent with existing clinical evidence, grade ≥3 neutropenia occurred more often with docetaxel (15%) than with paclitaxel (5%) or nab-paclitaxel (2%).

AEs led to discontinuation of pertuzumab in 10% of cases, trastuzumab in 9%, and the taxane in 20%. Heart failure and decreased ejection fraction were the most common reasons for discontinuation of pertuzumab and trastuzumab, whereas peripheral neuropathy, peripheral sensory neuropathy, and paresthesia accounted for the most taxane discontinuations.

After a median follow-up of 5.7 years, median PFS was 19.4 months in the docetaxel group, 23.2 months with paclitaxel, and 19.2 months with nab-paclitaxel. Median OS was 66.5 months with docetaxel, 64.0 months with paclitaxel, and 70.9 months with nab-paclitaxel.

In CLEOPATRA, the median PFS was 18.7 months and the median OS was 56.5 months among patients randomized to dual anti-HER2 therapy.

Although PERUSE was not designed to compare outcomes across the three taxane groups, “the choice of taxane did not seem to affect the survival outcomes,” noted authors of an accompanying editorial. Beyond the taxane issue, the trial demonstrated the transferability of the CLEOPATRA results to routine clinical practice.

“The patients enrolled in the PERUSE study better mirror those treated in our daily clinical practice,” said Elie Rassy, MD, and Barbara Pistilli, MD, of Gustave Roussy Cancer Institute in Villejuif, France.

In contrast to CLEOPATRA, PERUSE enrolled more patients who had received adjuvant or neoadjuvant trastuzumab and more patients who had hormone receptor-positive disease and received maintenance endocrine therapy. Previous exposure to anti-HER2 therapy was associated with shorter PFS and OS, consistent with “real-life evidence.”

PERUSE left some questions unresolved, Rassy and Pistilli continued. Potential differences in long-term quality-of-life effects among the taxanes remain undetermined. Additionally, the relevance of the findings to newer therapies that are being used more often, such as trastuzumab-emtansine (T-DM1; Kadcyla) have yet to be examined.