The role of volume of disease for treatment selection in patients with metastatic castration sensitive prostate cancer (mCSPC): A living meta-analysis.

Authors

null

Syed Arsalan Ahmed Naqvi

Mayo Clinic, Phoenix, AZ

Syed Arsalan Ahmed Naqvi , Irbaz Bin Riaz , Huan He , Manal Imran , Jacob Orme , Daniel S Childs , Praful Ravi , Syed A. Hussain , Parminder Singh , Alan Haruo Bryce

Organizations

Mayo Clinic, Phoenix, AZ, Dana-Farber Cancer Institute, Boston, MA, Mayo Clinic Department of Digital Health, Rochester, MN, Dow Medical College, Karachi, Pakistan, Mayo Clinic Department of Pediatric and Adolescent Medicine, Rochester, MN, Mayo Clinic, Rochester, MN, University of Sheffield, Sheffield, United Kingdom

Research Funding

No funding received
None.

Background: Previous evidence suggests that there may be no additional benefit of triplet therapy in low volume disease based on limited data. Therefore, we investigated the efficacy of triplet therapy as compared to docetaxel (D) and androgen pathway inhibitor (API) doublets by volume of disease using the most up to date results from the ARASENS trial. Methods: Phase III randomized controlled trials (RCTs) assessing treatment intensification with API, and/or D in patients with mCSPC were included. Precomputed hazard ratios (HR) with 95% confidence intervals (CI) for OS were pooled using an inverse-variance approach. A DerSimonian-Laird random-effects meta-analysis was conducted to assess the efficacy of triplet therapy compared to D doublet therapy. P-value of interaction was computed to assess difference between high (HV) and low volume (LV) disease subgroups (Pint <0.1 - statistical significance). Additionally mixed treatment comparisons were computed using network meta-analysis (NMA) to assess the comparative effectiveness of triplet therapy compared to API doublets by volume of disease. Results: Pairwise meta-analysis included a total of 3 RCTs (ARASENS, PEACE-1, ENZAMET) with 2518 patients (HV: 1820; LV: 698) as shown. In patients with HV disease, 385 (43%) and 484 (53%) deaths were observed with triplet therapy, and D doublet, respectively. Triplet therapy significantly improved OS as compared to D doublet in HV (HR: 0.73; 95% CI: 0.64-0.84). In patients with LV disease, 73 (20%) and 94 (28%) deaths were observed with triplet therapy, and D doublet, respectively. Triplet therapy significantly improved OS as compared to D doublet in LV (HR: 0.71; 95% CI: 0.52-0.97). There was no statistically significant interaction by volume of disease for triplet therapy vs. D doublet (Pint: 0.86). NMA including 10 clinical trials and over 11500 patients updated as of 13th Feb 2023 showed that in HV mCSPC, triplet therapy was ranked as potentially the most efficacious treatment option and may improve OS compared to API doublet therapy (HR: 0.83; 95% CI: 0.66-1.03). In LV mCSPC, API doublet therapy was ranked as potentially the most efficacious treatment followed by triplet therapy. There was no significant difference between triplet therapy and API doublet therapy (HR: 1.12; 95% CI: 0.74-1.12). Conclusions: These results underscore that triplet therapy may be preferred in mCSPC patients with HV disease whereas API doublet therapy may be preferred in LV disease.

Overall SurvivalAnticipated absolute effects
SubgroupParticipants (trials)Hazard ratio (95% CI)Risk of death with D doubletRisk difference with triplet therapy
Volume of disease
High volume1820 (3 trials)0.73
(0.64 to 0.84)
530 deaths per 1,000106 fewer per 1,000;
(147 fewer to 60 fewer)
Low volume698 (3 trials)0.71
(0.52 to 0.97)
280 deaths per 1,00072 fewer per 1,000;
(123 fewer to 7 fewer)

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Abstract Details

Meeting

2023 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Genitourinary Cancer—Prostate, Testicular, and Penile

Track

Genitourinary Cancer—Prostate, Testicular, and Penile

Sub Track

Prostate Cancer– Advanced/Hormone-Sensitive

Citation

J Clin Oncol 41, 2023 (suppl 16; abstr 5088)

DOI

10.1200/JCO.2023.41.16_suppl.5088

Abstract #

5088

Poster Bd #

182

Abstract Disclosures

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