Etirinotecan pegol does not prolong survival when compared with physician’s choice of chemotherapy in patients with breast cancer and brain metastases, according to results of the phase 3 ATTAIN trial published in JAMA Oncology.1

“The study results, although not positive, represent the largest published trial dedicated to this understudied population of patients with breast cancer and brain metastases and may help inform future research,” the researchers wrote.

The researchers conducted the ATTAIN trial because results from a subanalysis of the phase 3 BEACON study suggested that etirinotecan pegol may provide an overall survival (OS) benefit for patients with stable, pretreated brain metastases.2 


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The ATTAIN trial (ClinicalTrials.gov Identifier: NCT02915744) included 178 patients with metastatic breast cancer and stable, pretreated brain metastases. All patients had experienced disease progression while receiving chemotherapy in the metastatic setting.

The patients were randomly assigned to receive etirinotecan pegol (n=92) or physician’s choice of chemotherapy (n=86). Physicians’ choice treatments included eribulin (n=34), vinorelbine (n=17), gemcitabine (n=16), nab-paclitaxel (n=7), paclitaxel (n=5), ixabepilone (n=4), and docetaxel (n=3).

Baseline characteristics were well balanced between the treatment arms. Most patients had hormone receptor-positive and HER2-negative disease (45% in the etirinotecan pegol arm and 46% in the physician’s choice arm) or triple-negative disease (40% in both arms). Most patients had received at least 4 prior treatment regimens (88% in the etirinotecan pegol arm and 91% in the physician’s choice arm). 

There was no significant difference in OS between the treatment arms. The median OS was 7.8 months with etirinotecan pegol and 7.5 months with physician’s choice chemotherapy (hazard ratio [HR], 0.90; 95% CI, 0.61-1.33; P =.60). The 6-month OS rates were 63.4% and 62.1%, respectively. The 12-month OS rates were 32.7% and 31.2%, respectively.

Overall, the median progression-free survival (PFS) was 2.1 months with etirinotecan pegol and 1.9 months with physician’s choice (HR, 0.59; 95% CI, 0.38-0.91; P =.02). 

Among patients with central nervous system (CNS) metastases, the median PFS was 3.9 months with etirinotecan pegol and 3.3 months with physician’s choice (HR, 0.59; 95% CI, 0.33-1.05; P =.07). Among patients without CNS metastases, the median PFS was 2.8 and 1.9 months, respectively (HR, 0.72; 95%CI, 0.45-1.16; P =.18)

Treatment discontinuation due to adverse events (AEs) occurred more frequently with etirinotecan pegol than with physician’s choice — 10% and 1.3%, respectively. The most common grade 3 or higher AEs in the etirinotecan pegol group were diarrhea (13.3%), neutropenia (7.8%), and fatigue (6.7%).

Serious treatment-related AEs occurred in 20% of patients treated with etirinotecan pegol and 11.7% of patients who received physician’s choice chemotherapy. There were 3 deaths due to AEs in the etirinotecan pegol arm and none in the physician’s choice arm.

“The phase 3 ATTAIN randomized clinical trial did not replicate the positive OS benefit of treatment with etirinotecan pegol compared with chemotherapy in patients with breast cancer and BM [brain metastasis] that was observed in BEACON, emphasizing the need to closely mirror the original trial design in confirmatory studies,”  the researchers wrote. 

They added that these results “highlight the importance of confirming findings from subgroup analyses.”

Disclosures: This study was funded by Nektar Therapeutics. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

References

1. Tripathy D, Tolaney SM, Seidman AD, et al. Treatment with etirinotecan pegol for patients with metastatic breast cancer and brain metastases. Final results from the phase 3 ATTAIN randomized clinical trial. JAMA Oncol. Published online May 12, 2022. doi:10.1001/jamaoncol.2022.0514

2. Cortés J, Rugo HS, Awada A, et al. Prolonged survival in patients with breast cancer and a history of brain metastases: Results of a preplanned subgroup analysis from the randomized phase III BEACON trial. Breast Cancer Res Treat. 2017;165(2):329-341. doi:10.1007/s10549-017-4304-7