Refining who gets the ‘kitchen sink’
Dr. Arteaga highlighted two trials focused on the immune checkpoint inhibitor pembrolizumab.
The phase 3 KEYNOTE-522 study led to the approval of neoadjuvant pembrolizumab plus chemotherapy for early-stage triple-negative breast cancer (TNBC) in July 2021. At this year’s SABCS, researchers will present new data from KEYNOTE-522 (abstract GS1-01), representing final results from the trial’s event-free survival (EFS) outcome.
Previously, investigators reported a statistically significant and clinically meaningful improvement in EFS. These data suggest “that deploying immunotherapy early before surgery ... may be curative in some patients,” Dr. Arteaga said. The new data will allow the “robustness and consistency” of the earlier findings to be assessed.
But, he added, this is a “tough” treatment, which includes five drugs. “It’s the kitchen sink, and not everybody needs the kitchen sink. It’s important to refine these findings. Some patients may not need pembrolizumab, but some do.”
The second trial exploring pembrolizumab – KEYNOTE-355 (abstract GS1-02) – mirrors KEYNOTE-522 but in patients with previously untreated locally recurrent inoperable or metastatic TNBC whose tumors expressed PD-L1.
Previously, investigators reported that pembrolizumab combined with chemotherapy showed statistically significant improvements in overall survival and PFS compared to placebo plus chemotherapy. At the 2021 SABCS, researchers will provide final study results, including outcomes in subgroups of patients by additional combined positive score cutoffs.
Metformin trial: ‘This is it’
Dr. Arteaga highlighted CCTGMA.32 (abstract GS1-08), a phase 3 randomized, placebo-controlled adjuvant trial of the diabetes drug metformin versus placebo in early breast cancer. Results of the primary efficacy analysis of the trial will be presented at the meeting.
The Canadian-led study seeks to determine if metformin can decrease breast cancer cell growth and work with cancer therapies to prevent disease recurrence. The study design calls for patients to take twice-daily oral metformin or placebo pills for up to 5 years in the absence of disease progression.
The primary outcome of the 3,500-plus patient trial is invasive disease-free survival in hormone receptor (ER and PgR) negative and positive (ER and/or PgR) subgroups.
“Metformin has actually been associated with improved survival [in breast cancer] in patients on chemotherapy. But we don’t know exactly how,” he said. “There’s never been a head-to-head comparison in the adjuvant setting [before]. This is it.”
TKI for breast cancer with brain mets
The SABCS codirector spotlighted an updated overall survival analysis of the randomized phase 3 PHOEBE trial (abstract GS3-02).
Previous research confirmed the superiority of pyrotinib, a novel TKI targeting HER1, HER2, and HER4, over lapatinib when given in combination with capecitabine in HER2-positive metastatic breast cancer.
In the United States, the lapatinib-capecitabine combination is “mostly used” in patients with HER2 metastatic disease and brain metastases who also undergo stereotactic radiation, Dr. Arteaga said.
This use has continued despite groundbreaking results from the HER2CLIMB trial, featuring the TKI tucatinib, he said.
As reported last year, adding tucatinib to trastuzumab and capecitabine in patients with HER2-positive breast cancer and brain metastases increased median overall survival from 12 months to 18.1 months. The results were called the first of their kind at that time.
The pyrotinib study may matter to American clinicians because pyrotinib is used mostly in China, not the United States, and this analysis suggests that pyrotinib could be part of the armamentarium in the United States, alongside tucatinib.
TKIs are like Coke and Pepsi, Dr. Arteaga said: “Similar but not identical.” Therefore, it is worth taking a look at the new study, he said. “There may be some benefit in having more than one [TKI] in the therapeutic armamentarium.”
Dr. Arteaga receives or has received grant support from Pfizer and Lilly and serves or has served in a scientific advisory role with Novartis, Lilly, TAIHO Oncology, Daiichi Sankyo, Merck, AstraZeneca, OrigiMed, Immunomedics, ARVINAS, Sanofi, Athenex, and the Susan G. Komen Foundation. He also holds minor stock options from Provista.
A version of this article first appeared on Medscape.com.