KEY TAKEAWAYS
- The phase 3 CLEOPATRA study assessed the relationship between survival outcomes and initial tumoral response to the combination of D+T+P in metastatic HER2-positive BC.
- The trial’s primary objective was to evaluate the OS of pts. PFS was the secondary objective.
- The study suggested that an early complete radiological response to the D+T+P treatment results in longer overall and progression-free survival than partial or stable responses.
The standard initial treatment for metastatic HER2-positive breast cancer, as per the CLEOPATRA trial, involves using docetaxel (D) in combination with trastuzumab and pertuzumab (T+P). But, not all patients (pts) experience the same level of benefit from this therapy. The study investigated the relationship between survival outcomes and the initial tumor response to D+T+P.
Researchers conducted an exploratory analysis of the CLEOPATRA trial using data retrieved from the Vivli database (ID:00007856). The primary purpose was to evaluate the overall survival (OS) of pts receiving treatment with D+T+P based on their response to the initial tumor assessment conducted at nine weeks. The secondary objective was to examine progression-free survival (PFS). Responses were categorized as complete (CR), partial (PR), or stable (SD), following RECIST 1.0 criteria, as assessed through central review as per the original trial. Patients who did not undergo the first tumor assessment were excluded from the analysis. A log-rank test was conducted to compare the Kaplan-Meier survival curves, and uni- and multivariate analyses were conducted. The study applied the Extended Cox Regression Model for any potential guarantee-time bias.
The D+T+P arm of the study included 362 out of 402 pts; 12.7% (46/362) achieved CR, 67.1% (243/362) had PR, and 20.2% (73/362) had SD. Within the CR group, 47.8% of pts had de novo disease (61.3% in PR, 43.8% in SD, p=0.015 based on Fisher’s exact test), 69.6% of the CR group had visceral disease (83.3% in PR and 67.1% in SD (p=0.005). 60.9% of the CR group was HR negative (51.9% in PR and 49.3% in SD, showing no significant difference). Following a median follow-up of 4.1 years, pts in the CR group exhibited longer PFS compared to those in the PR or SD groups (log-rank p<0.001) and a longer OS compared to the PR or SD groups (median OS not reached in the CR group), 57.3 mos (interquartile range 32.1-NR) in the PR group, and 43.4 mos (interquartile range 22-103.5) in the SD group (p=0.002). A multivariate analysis demonstrated that a high body mass index was associated with improved OS in the SD group (HR=0.93, 95% CI 0.88-0.99, p=0.023), while an ECOG score of ≥1 was associated with worse OS in the PR group (HR=1.66, 95% CI 1.17-2.36, p=0.005). The survival benefit of CR was similar in both HR-negative and HR-positive tumors (p=NS).
The study concluded that achieving an early radiological CR with D+T+P results in extended OS and PFS, but no distinction is observed compared to PR and SD groups.
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT00567190
Debien, V., Agostinetto, E., Bruzzone, M., Ceppi, M., Molinelli, C., Martins Branco, D., Jacobs, F., Nader Marta, G., Lambertini, M., de Azambuja, E. THE IMPACT OF INITIAL TUMOR RESPONSE TO DOCETAXEL, TRASTUZUMAB, AND PERTUZUMAB ON SURVIVAL OUTCOMES OF PATIENTS WITH HER2+ METASTATIC BREAST CANCER: AN EXPLORATORY ANALYSIS OF THE CLEOPATRA TRIAL. Annals of Oncology (2023) 8 (1suppl_4): 101223-101223. 10.1016/esmoop/esmoop101223
