But sometimes the takeaways are less clear-cut and more controversial, like whether to change practice on the basis of the results of phase 3, placebo-controlled, randomized KEYNOTE 522 trial (ClinicalTrials.gov identifier: NCT03036488).3 According to Dr Wisinski, the KEYNOTE 522 trial is currently the “most-debated” study from SABCS 2019.
First presented at SABCS, a preplanned interim analysis of the KEYNOTE 522 trial showed that for patients with triple-negative breast cancer (TNBC), adding pembrolizumab to neoadjuvant chemotherapy may have a clinical benefit according to the coprimary endpoints of pathological complete response (pCR) and event-free survival (EFS).
Patients who received neoadjuvant chemotherapy with pembrolizumab had a higher pCR rate than patients who received neoadjuvant chemotherapy with placebo (64.8% vs 51.2%), a difference that was statistically significant (P =.00055). However, although patients who received neoadjuvant chemotherapy with pembrolizumab had a higher EFS at a median follow-up of 15.5 months than patients who received neoadjuvant chemotherapy with placebo (91.3% vs 85.3%), the difference was not yet statistically significant at the time of the presentation. Further follow-up would likely be needed to make a solid conclusion either way.
Session panelist Nadia Harbeck, MD, PhD, Ludwig Maximilian University of Munich, Germany, who was involved in the trial, said that results “could” change practice and “probably will” once there is approval — but she cautioned that the trial is ongoing and oncologists should wait for approval. Pembrolizumab is not currently approved in the United States for patients with TNBC.
Speaking broadly about immunotherapy data reported at SABCS, Dr Harbeck advised against off-label use of “any” immunotherapy or “any” chemotherapy based solely on just the hope that it will work for patients with TNBC. “We should take the evidence-based regimens,” she emphasized.
According to Dr Kaklamani, to have a dialogue about the results of KEYNOTE 522 is exactly why this type of conference session was created.
But, “the results are not completely final at this point,” she observed. Also, adding pembrolizumab to neoadjuvant chemotherapy increases not only the toxicity of the regimen, but also the cost of the treatment.
The interim analysis showed the patients who received neoadjuvant chemotherapy with pembrolizumab had a higher incidence of any-grade immune-mediated adverse events (32.1% vs 10.8%), grade 3 through grade 5 immune-mediated adverse events (12.0% vs 1.0%), and drug discontinuation (6.5% vs 0.8%) compared with patients who received neoadjuvant chemotherapy with placebo.
On the other hand, the reality is this is a population of patients that tends to have poor outcomes and needs more therapeutic options. “When a patient comes to you and she’s 25 years old and she has a large triple-negative breast cancer with positive lymph nodes, you want to do the best you can for her to not have a recurrence of her disease,” said Dr Kaklamani. “If the KEYNOTE data suggest that [adding pembrolizumab] might be the case, then you want to act on it.”
“That’s kind of a debate that we have every day in clinic: We have data that we may not be able to be ready to act on, but our patients are here,” said Dr Kaklamani. “They’re not going to wait — cancer doesn’t wait.”
- Piccart M, Procter M, Fumagalli D, et al. Interim overall survival analysis of APHINITY (BIG 4-11): A randomized multicenter, double-blind, placebo-controlled trial comparing chemotherapy plus trastuzumab plus pertuzumab versus chemotherapy plus trastuzumab plus placebo as adjuvant therapy in patients with operable HER2-positive early breast cancer. Oral presentation at: 2019 San Antonio Breast Cancer Symposium; December 10-14, 2019; San Antonio, TX. Abstract GS1-04.
- Tolaney SM, Trippa L, Barry W, et al. TBCRC 033: A randomized phase II study of adjuvant trastuzumab emtansine (T-DM1) vs paclitaxel (T) in combination with trastuzumab (H) for stage I HER2-positive breast cancer (BC) (ATEMPT). Oral presentation at: 2019 San Antonio Breast Cancer Symposium; December 10-14, 2019; San Antonio, TX. Abstract GS1-05.
- Schmid P, Park YH, Marta Ferreira M, et al. Keynote-522 study of pembrolizumab + chemotherapy vs placebo + chemotherapy as neoadjuvant treatment, followed by pembrolizumab vs placebo as adjuvant treatment for early triple-negative breast cancer: Pathologic complete response in key subgroups. Oral presentation at: 2019 San Antonio Breast Cancer Symposium; December 10-14, 2019; San Antonio, TX. Abstract GS3-03.