(UroToday.com) The 2023 American Society of Clinical Oncology (ASCO) annual meeting held in Chicago, IL between June 2nd and June 6th was host to a prostate, testicular, and penile cancers poster session. Dr. Ryan Phillips presented an analysis of the NRG Oncology/RTOG 0521 phase III trial evaluating the benefit of adding docetaxel to definitive radiotherapy based on basal-luminal subtyping of localized, high-risk prostate cancer patients.
Prior studies have demonstrated that basal/luminal subtyping predicts a differential treatment response to androgen suppression of high-risk prostate cancer, based on results of the NRG-GU-TS006, whereby patients with basal subtype prostate cancer appeared to benefit the most from longer durations of ADT, compared to those with the luminal subtype who did not confer such a benefit.1 Conversely, analysis of the CHAARTED trial in the mHSPC disease space has demonstrated that patients with luminal subtype prostate cancers derive the greatest benefit from treatment intensification with chemotherapy. In this study, Dr. Phillips and colleagues evaluated whether basal-luminal subtyping predicts differential responses to chemotherapy addition in the setting of high-risk prostate cancer treated with radiotherapy plus ADT within the NRG/RTOG 0521 trial.
In accordance with a pre-specified and approved NCI analysis plan, the investigators obtained available NRG biobank biopsy specimens from patients enrolled in the NRG/RTOG 0521 phase III trial, which randomized patients to radiotherapy plus long-term ADT, with or without adjuvant chemotherapy.2 The highest-grade tumors were profiled on clinical-grade whole-transcriptome arrays (Veracyte, San Diego, CA). Basal-luminal subtypes were generated using a 215-gene PCa subtyping classifier (PSC), a second generation PAM50 basal-luminal model. Cox regression modeling was used to evaluate the associations between basal-luminal subtyping (luminal proliferating [LP] and non-LP) and overall survival (OS) and metastasis-free survival (MFS), whereas Fine and Gray modeling was used to evaluate the outcome of distant metastasis. Analyses were performed by treatment arm, and the multivariable models were adjusted for age and trial risk stratification.
Of the 183 samples available for analysis (91 from control and 92 from the chemotherapy arm), 52 (28%) were classified as LP subtype. The median follow-up for OS was 9.9 years. No significant differences in clinical or pathological variables were observed between LP and non-LP subtypes.
On multivariable analysis, the investigators did not detect any significant LP subtype-by-chemotherapy treatment interaction but observed evidence of non-proportional hazards (Grambsch-Therneau test, p<0.05). In unselected patients, the 5- and 10-year OS restricted mean survival time (RMST) difference between the arms was 0.9 (95% CI: -1.5 to 3.4, p=0.46) and 5.7 months (95% CI: -2.5 to 13.9, p=0.17), respectively. Stratifying by tumor subtype, the RMST difference at 5 years was:
- LP: 3.8 months (95% CI: 0.3 to 7.2, p=0.03)
- Non-LP: -0.2 months (95% CI: -3.4 to 2.9, p=0.89)
The RMST difference at 10 years by subtype was:
- LP: 13.7 months (95% CI: -0.2 to 27.5, p=0.053)
- Non-LP: 2.5 months (95% CI: -7.6 to 12.5, p=0.63)
Dr. Philips concluded that luminal-basal subtyping of prostate cancer tissue, using pre-treatment biopsy samples from a Phase 3 trial cohort of localized high-risk men, demonstrated differential responses to docetaxel chemotherapy. Similar to results from the CHAARTED trial of metastatic disease, luminal proliferating tumors may derive greater benefit from addition of chemotherapy. Validation of these findings may enable effective earlier use of chemotherapy in men with PCa.
Presented by: Ryan Phillips, MD, Ph.D., Assistant Professor, Department of Radiation Oncology, Mayo Clinic, Rochester, MN
Written by: Rashid Sayyid, MD, MSc – Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @rksayyid on Twitter during the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago, IL, Fri, June 2 – Tues, June 6, 2023.
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