No predictive biomarkers found in PALLAS

PAM50 subtype does not predict 5-year invasive disease-free survival (IDFS) nor benefit of adjuvant palbociclib in patients with stage II–III HR-positive/HER2-negative early breast cancer, as was shown by biomarker analysis of the phase 3 PALLAS trial.

The use of CDK4/6 inhibitors combined with endocrine therapy is a standard-of-care for advanced/metastatic HR-positive/HER2-negative breast cancer, supporting the rationale to study CDK4/6 inhibition in the early breast cancer setting. Recently, the phase 3 PALLAS trial (NCT02513394) did not show survival benefit of 2 years of adjuvant palbociclib plus endocrine therapy versus endocrine therapy alone in patients with stage II–III HR-positive/HER2-negative early breast cancer [1]. A protocol-defined biomarker analysis (TRANS-PALLAS) was performed in which genomic subtype (PAM50 intrinsic subtype) from whole-transcriptome RNA sequencing was used for analysis of prediction and prognosis. Dr Daniel Stover (The Ohio State University, OH, USA) presented the outcomes [2].

From the total study population of 5,796 enrolled patients, tumour samples of 1,748 patients (889 in the palbociclib arm, 859 in the placebo arm) were included in TRANS-PALLAS. Risk for 5-year IDFS in the TRANS-PALLAS cohort appeared to be significantly lower relative to the rest of the PALLAS population (P=0.0013).

Based on PAM50 determination, 72.1% of the tumours in the TRANS-PALLAS cohort were luminal A, 2.6% normal, 10.5% luminal B, 4.1% HER2-like, and 3.8% basal-like subtype. Although heterogeneity was observed in 5-year IDFS by PAM50 subtypes (87.1% IDFS in luminal A vs 75.8% IDFS in basal-like subtype), no statistically significant association was observed (P=0.066). Likewise, heterogeneity between PAM50 subtypes was found regarding palbociclib benefit (HR 1.33 in basal-like vs HR 0.25 in HER2-like subtype), but this interaction was also not statistically significant (P=0.145).

Both PAM50 risk of recurrence (ROR) score and PAM50 proliferation score were prognostic for 5-year IDFS. In addition, a potential interaction was observed for PAM50 ROR and PAM50 proliferation score with palbociclib treatment benefit (P=0.051).

Based on these outcomes. Dr Stover concluded that “the biomarker analysis revealed a higher than anticipated percentage of luminal A tumours in the TRANS-PALLAS cohort, indicating a lower-risk distribution of cancers in this population. PAM50 subtype did not appear to be prognostic or predictive for palbociclib benefit.”

1. Gnant M, et al. J Clin Oncol. 2022;40:282-293.
2. Stover D, et al. Protocol-defined biomarker analysis in the PALLAS adjuvant trial (AFT-05; ABCSG-42): Genomic subtype derived from RNA sequencing of HR+/HER2- early breast cancer. Abstract GS03-07, SABCS 2023, 5–9 December, San Antonio, TX, USA.

 

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Posted on 11 January 202411 January 2024