KEY TAKEAWAYS
- The TATEN phase II trial aimed to assess the efficacy, safety, and potential predictive biomarkers of pembro+ paclitaxel in HR+/HER2-negative, PAM50 nonluminal, ABC patients.
- The primary endpoint was ORR.
- The results showed safe and promising efficacy in CDK4/6i resistant HR+/HER2- ABC, but premature enrollment termination was attributed to funding and pembro supply constraints.
In HR+/HER2-negative breast cancer, PAM50 non-luminal tumors, such as HER2-enriched (HER2-E) and Basal-like subtypes, exhibit elevated expression of proliferation and immune-related genes, along with increased tumor infiltrating lymphocytes. This suggests a potential benefit from immunotherapy in this specific subset.
Aleix Prat and his research team designed the first study that aimed to evaluate the efficacy, safety, and correlative analysis of the combination of pembrolizumab (pembro) and paclitaxel in patients with HR+/HER2-negative, PAM50 non luminal advanced breast cancer (ABC).
The study included patients meeting key criteria of progression after CDK4/6 inhibitors, measurable disease, no prior ABC chemotherapy, ECOG 0-1, and non-luminal metastatic disease by PAM50. Participants received pembrolizumab (200 mg every 3 weeks from cycle 1) with paclitaxel (80 mg/m2 weekly from cycle 2). The primary endpoint was RECIST V1.1-based overall response rate (ORR) in the evaluable population. Secondary endpoints encompassed progression-free survival (PFS), clinical benefit rate (CBR), safety, and predictive biomarkers.
Employing a Simon two-stage design, Stage I success required ≥6 of 15 patients achieving a partial or complete response (CR), leading to recruitment of up to 46 evaluable patients for a target ORR ≥41%. Metastatic biopsies from pre-screening were analyzed for tumor-infiltrating lymphocytes (TILs) and a 192-gene panel, including PDL1 and PD1 expressions.
Of 132 screened tumors, 27 (20%) were identified as PAM50 non-luminal. Non-luminal tumors exhibited a trend towards higher PDL1 expression (P=0.090) and TILs (P=0.084) compared to luminal tumors, with no significant difference observed for PD1 (P=0.850). Among the 20 recruited patients (Stage I+II), 18 were evaluable. Baseline characteristics included a median age of 55 years, 55% with ECOG 0, 22% with de novo metastatic breast cancer (MBC), and 72.2% with visceral disease.
About 13 patients (72.2%) discontinued treatment due to progressive disease, 3 (16.6%) due to toxicity, and 2 (11.1%) were still on treatment. ORR was 61.1% (11 of 18 95% CI 35.7-82.7), CBR was 88.9% (16 of 18 95% CI 65.3-98.6), and median PFS was 8.3 months (95% CI 7.3 – 14.1).
Treatment-related adverse events (TRAEs) occurred in 95% of patients (any grade), with 45% experiencing G3 TRAEs. No G4 or G5 TRAEs were reported. Gene expression analysis for all patients revealed associations between PFS and luminal A signature (P=0.049), as well as luminal genes PGR (P=0.028) and RRAGA (P=0.038) indicating worse outcomes. Conversely, the pan-leucocyte receptor CD84 (P=0.028) was associated with better PFS.
The combination of pembrolizumab and paclitaxel demonstrates safety and promising efficacy in HR+/HER2- advanced breast cancer with CDK4/6 inhibitor resistance and a PAM50 non luminal subtype. Despite meeting stage II criteria, premature enrollment cessation resulted from insufficient funding and pembrolizumab supply.
Further correlative analyses will be presented at the conference. Research was funded by SOLTI Breast Cancer Research Group.
Source: https://atgproductions.net/atgclients/sabcs/2023_SABCS_Abstract_Report-12-1-23_Compressed.pdf
Clinical Trial: https://clinicaltrials.gov/study/NCT04251169
Prat A, Conte B, Brasó-Maristany F et al. (2023) ‘’Solti-1716 TATEN phase II trial: Targeting non-Luminal disease by PAM50 with pembrolizumab and paclitaxel in Hormone Receptor-positive/HER2-negative advanced breast cancer (ABC).’’ Presented at SABCS 2023 (PO1-06-02).
