New Drugs Show Promise in Triple-Negative, HER2-Positive Breast Cancer

With many recent developments in the treatment landscape for breast cancer, a session at the Community Oncology Alliance virtual 2021 conferenceon Thursday reviewed some exciting new data and approvals for triple-negative breast cancer (TNBC) and human epidermal growth factor receptor 2 (HER2)-positive breast cancer.

Presenter Joyce A. O’Shaughnessy, MD, began her discussion with a review of several recent clinical trials in patients with TNBC. First, she said the IMpassion130 trial examined nabpaclitaxel in combination with atezolizumab and found improvements in overall survival (OS). However, she noted that the IMpassion131 trial—which investigated paclitaxel either with or without atezolizumab—showed no improvement in OS when atezolizumab was added.

“We really are a bit flummoxed,” O’Shaughnessy said, adding that there must have been unseen prognostic variables that made the control group overperform so substantially.

Turning her attention to the recent approval of pembrolizumab in combination with chemotherapy for patients with TNBC, O’Shaughnessy said researchers found that 38% of patients had a combined positive score of 10% or more, although they have not yet seen survival data from this study.

Preoperative trials have been ongoing in this patient population, with experts hoping to have approvals for checkpoint inhibitors in addition to preoperative chemotherapy, O’Shaughnessy said. The KEYNOTE-522 study, which is investigating checkpoint inhibitors in preoperative patients, found a 13.6% improvement in pathologic complete response (pCR) in breasts and lymph nodes.

Similarly, O’Shaughnessy said the KEYNOTE-355 study is finding promising data on event-free survival, although the median follow-up for that study is still just 15.5 months. O’Shaughnessy said she is hoping for another interim analysis later in 2021, which could potentially lead to an approval in the preoperative and neoadjuvant setting.

Finally, O’Shaughnessy reviewed the approval of sacituzumab govitecan, a TROP-2 targeted antibody drug conjugate that was approved on April 7. She said clinical trials of this drug showed huge improvements in OS from 6 to 12 months compared to a single-agent chemotherapy.

“This is a marvelous result, and this has been very well utilized now in later tNBC,” O’Shaughnessy said.

Next, O’Shaughnessy reviewed recent developments in the treatment of HER2-positive breast cancer. Tucatinib very selectively inhibits HER2, she said, allowing it to get great brain penetration. The randomized HER2CLIMB trial saw not only improvements in progression-free survival (PFS), but also a surprising improvement in OS with a statistically significant hazard ratio of 0.6, O’Shaughnessy said.

Notably, in patients with brain metastases, O’Shaughnessy said the HER2CLIMB trial saw a 55% reduction in risk of progression or death in the total patient population, potentially allowing clinicians to put off the use of radiation therapy in these patients.

Next, O’Shaughnessy discussed recent research on trastuzumab deruxtecan in heavily pre-treated patients with HER2-positive breast cancer and a median of 6 lines of prior therapy. Investigators found a median PFS of 19 months and a median OS of 24 months, which O’Shaughnessy said is significant.

Finally, the use of neratinib as post-neoadjuvant therapy for patients less than 1 year after treatment with trastuzumab is also showing promise. Investigators have found a 7.4% absolute improvement in invasive disease-free survival at 60 months and a 9.1% improvement in overall survival at 8 years, according to her presentation.

“I think this is a really important option for [estrogen receptor-positive] patients, along with endocrine therapy, to give them every change of remaining progression-free,” O’Shaughnessy concluded.

REFERENCE

O’Shaughnessy J. Managing New Drugs in Breast Cancer: Therapeutic Opportunities and Challenges; April 8, 2021. Presented at: Community Oncology Alliance Virtual 2021 Conference; Accessed April 8, 2021.