Fabrice André, MD, PhD
Fabrice André, MD, PhD, Professor of Medical Oncology at the Gustave Roussy Cancer Center, Villejuif, France, and Chairman of the Biomarker Group at UNICANCER, provided comments on the stage IIA cohort of the PALLAS trial. “The key message from PALLAS1 is there is no signal for efficacy of palbociclib in stage IIA breast cancer. The second message is the 4-year distant relapse–free survival was 95%,” he said.
“Two main questions arise from this presentation: What criteria should a drug meet when we make the decision to move it to the adjuvant setting (was palbociclib ready?)? What are the next research topics and how should we address them in patients with early-stage breast cancer?”
According to Dr. André, there were “convincing” data to justify studying palbociclib in the adjuvant setting, including “robust” progression-free survival results in PALOMA-22 in endocrine-sensitive or -naive patients and prior observations that palbociclib given shortly before surgery may reduce Ki67 levels. On the other hand, compliance in the adjuvant setting “can be less than anticipated,” and the mechanism of action of this class of drugs has not been well established. Additionally, palbociclib failed to improve overall survival in the metastatic setting.3
Steps to Improve Future Adjuvant Trials
“The failure of PALLAS has provided some suggestions to further improve trials in the adjuvant setting,” Dr. André said. They include the following steps:
- Better explore the efficacy of the drug in preoperative or adjuvant circulating tumor DNA (ctDNA)-driven phase II trials before moving to phase III adjuvant trials
- Characterize the mechanism of action before moving to the adjuvant setting
- Monitor compliance, dose reduction, and treatment discontinuation more closely
- Find the optimal duration of adjuvant treatment; de-escalation of treatment in early disease is important to patients.
Dr. André further emphasized the need to select only those patients at high risk for treatment. “The 4-year disease-free survival rate of 95% means the relapse rate is too low to develop drugs in the whole population of patients with stage IIA disease,” he reasoned. For this purpose, he maintained, current genomic tests and ctDNA are not accurate enough to be cost-effective in this setting. “We need to move to technology driven by artificial intelligence as a tool for selecting patients for more complex testing,” he suggested. “We need to enter a new era for patient stratification. What’s the risk, and can we decrease treatment duration?”
DISCLOSURE: Dr. André reported personal financial relationships with Novartis, Roche, GlaxoSmithKline, and AstraZeneca.
REFERENCES
1. DeMichele A, Dueck AC, Hlauschek D, et al: Adjuvant palbociclib in ER+ breast cancer (PALLAS Trial ABCSG-42/AFT-05/PrE0109/BIG-14-13): A preplanned analysis of the stage IIA cohort. ASCO Plenary Series. Abstract 390216. Presented October 18, 2022.
2. Finn RS, Martin M, Rugo HS, et al: Palbociclib and letrozole in advanced breast cancer. N Engl J Med 375:1925-1936, 2016.
3. Finn RS, Rugo HS, Dieras VC, et al: Overall survival with first-line palbociclib plus letrozole versus placebo plus letrozole in women with estrogen receptor–positive/human epidermal growth factor receptor 2–negative advanced breast cancer: Analyses from PALOMA-2. 2022 ASCO Annual Meeting. Abstract LBA1003. Presented June 4, 2022.
