ASCO GU 2020: Correlative Measures of Tumor Response in the Phase II GALAHAD Study

San Francisco, CA ( Approximately 50% of patients with metastatic castration-resistant prostate cancer (mCRPC) cannot be assessed for response using RECIST criteria highlighting a need for additional endpoints for early indication of clinical benefit. Circulating tumor cells (CTCs) are easily accessible, reflect tumor biology, and could measure treatment response beyond imaging and PSA. CTC0 (drop in CTC count to 0) and CTC conversion (drop from more than to less than 5 CTCs in 7.5 ml of blood) have both been demonstrated to correlate with overall survival in mCRPC.

GALAHAD is a phase 2 study of niraparib in men with mCRPC and bi-allelic DNA damage repair (DDR) defects. Men were required to have progressed on/after at least one line of taxane-based chemotherapy and one line of androgen receptor targeting therapy. No prior treatment with a PARP inhibitor of platinum-based chemotherapy was allowed. CTCs were collected at baseline and subsequent follow-up timepoints. In this analysis, investigators analyzed CTC correlative data in the BRCA1/2 altered patients from the GALAHAD cohort.

CTC conversion was seen in 49% of overall participants. CTC0 and CTC conversion (as shown below) were early indicators of response and were associated with longer time on therapy in patients with measurable or non-measurable disease.


Further, CTC0 and CTC conversion were both associated with longer overall survival.


CTC0 and CTC conversion was also associated with greater reduction in PSA:


The authors concluded that:

  • CTC0 and CTC conversion should be considered as a valid endpoint regardless of measurable or non-measurable disease in mCRPC
  • CTC0 and CTC conversion occur early in treatment and could serve as a surrogate endpoint for long-term benefit to support accelerated drug development in patients with mCRPC

Presented by: Dr. Matthew R. Smith is Director of the Genitourinary Oncology Program at Massachusetts General Hospital Cancer Center and an Associate Professor of Medicine at Harvard Medical School

Written by: Jacob Berchuck, MD, Medical Oncology Fellow at the Dana-Farber Cancer Institute (Twitter: @jberchuck) at the 2020 Genitourinary Cancers Symposium, ASCO GU #GU20, February 13-15, 2020, San Francisco, California
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