(UroToday.com) On the first day of the American Society for Clinical Oncology (ASCO) Genitourinary Cancer Symposium 2022, Poster Session A focused on the care of patients with prostate cancer. Dr. Sayegh presented a poster assessing associations between tumor mutational burden (TMB, as quantified by mutations per megabase) and treatment outcomes. In particular, the authors highlighted that the most clinically useful biomarkers provide predictively, not just prognostic information. Thus, following approval of pembrolizumab for patients with metastatic castration-resistant prostate cancer (mCRPC), the authors sought to assess treatment class-specific outcomes for patients receiving Immune Checkpoint Inhibitor (ICPI) therapy, as compared to taxane chemotherapy, by tumor mutational burden.
To do so, the authors performed a retrospective analysis of the association of genomic data with clinical variables and outcomes in cohort of patients with mCRPC treated between January 2011 and April 2021. Longitudinal de-identified clinical data were obtained from the electronic health records of approximately 280 U.S. academic or community-based cancer clinics, curated via technology-enabled abstraction by Flatiron Health and linked to genomic testing by Foundation Medicine (FoundationOne or FoundationOne CDx assays). Using this large dataset, the authors identified 45 patients (14 with TMB ≥ 10, 31 with TMB < 10) who received single-agent anti-PD1 axis ICPI and 696 (30 with TMB ≥ 10, 666 with TMB < 10) who received single-agent taxanes. Treatment allocation was performed at the discretion of the treating physician without randomization. Using propensity score weighting to account for between-group imbalances, the authors assed the time to next therapy (TTNT) and overall survival (OS).
Among the 741 patients included in the analysis, the median age was 70 (IQR: 64 – 76), the median PSA was 79.4 (IQR: 19.0 – 254), 108 (18.8%) were ECOG 2+, and 644 (86.9%) had received prior systemic treatments for mCRPC. Patients in the two treatment groups had comparable pre-therapy age, PSA, hemoglobin, alkaline phosphatase, prior second generation novel hormonal therapy use, and prior opioid use. However, patients receiving ICPI, as compared to taxanes, had higher ECOG scores (0, 1, 2+ respectively 13.9%, 55.6%, 30.6% vs. 29.4%, 52.6%, 18.8%, p = 0.057), and greater prior taxane use (73.3% vs. 53.7%, p = 0.01). Further, those patients receiving ICPI had higher TMB (median 3.5, IQR: 1.7 – 15 vs. median 2.5, IQR 1.3 – 3.8, p < 0.001),
Among patients with evaluable PSA response, TMB was not associated with a differential PSA response among those who received taxane chemotherapy.
In contrast, among those who received ICPI, PSA responses were more pronounced among those with high TMB.
The time to next treatment was significantly worse among patients with low TMB (<10) who received ICPI as compared to taxane chemotherapy (median 2.4 vs. 4.1 months; HR: 2.7, 95%CI: 1.7 – 4.0, p < 0.001). In contrast, for those patients with TMB ≥ 10, ICPI was associated with a longer time to next treatment compared to taxane use (median 8.0 vs. 2.4 months; HR: 0.37, 95%CI: 0.15 – 0.87, p = 0.022). A similar pattern emerged for overall survival with numerically worse OS among patients with low TMB who received ICPI (median 4.2 vs. 6.0 months, HR: 1.08; 95%CI: 0.68– 1.7, p = 0.73) but longer OS among those with high TMB who received ICPI (median 19.9 vs. 4.2 months; HR: 0.23, 95%CI: 0.10 – 0.57, p = 0.0085).
In addition to TMB, the authors assessed for high microsatellite instability (MSI-H). This was less common (n=22) than high TMB (N=44), though 20 patients had both. Treatment interactions with TMB ≥ 10 (TTNT: p < 0.001, OS: p = 0.021) were stronger than MSI-H (TTNT: p = 0.0038, OS: p = 0.080).
Thus, the authors conclude that TMB may be a predictive biomarker to inform the choice if ICPI, rather than taxane chemotherapy, for patients with mCRPC with TMB ≥ 10.Presented by: Nicolas Sayegh MD, Huntsman Cancer Institute-University of Utah Health Care, Salt Lake City, UT