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Clinical Trial
. 2024 Jul 1;7(7):e2419966.
doi: 10.1001/jamanetworkopen.2024.19966.

Bone Pain and Survival Among Patients With Metastatic, Hormone-Sensitive Prostate Cancer: A Secondary Analysis of the SWOG-1216 Trial

Georges Gebrael  1 , Yeonjung Jo  1 , Umang Swami  1 , Melissa Plets  2 , Chadi Hage Chehade  1 , Arshit Narang  1 , Shilpa Gupta  3 , Zin W Myint  4 , Nicolas Sayegh  1 , Catherine M Tangen  5 , Maha Hussain  6 , Tanya Dorff  7 , Primo N Lara Jr  8 , Seth P Lerner  9 , Ian Thompson  10 , Neeraj Agarwal  1
Affiliations
Clinical Trial

Bone Pain and Survival Among Patients With Metastatic, Hormone-Sensitive Prostate Cancer: A Secondary Analysis of the SWOG-1216 Trial

Georges Gebrael et al. JAMA Netw Open. .

Abstract

Importance: The presence of bone pain is significantly associated with worse overall survival (OS) in patients with castration-resistant prostate cancer. However, there are few data regarding bone pain and survival outcomes in the context of metastatic, hormone-sensitive prostate cancer (MHSPC).

Objective: To compare survival outcomes among patients with MHSPC by presence or absence of baseline bone pain at diagnosis.

Design, setting, and participants: This post hoc secondary analysis, conducted from September 1 to December 31, 2023, used patient-level data from SWOG-1216, a phase 3, prospective randomized clinical trial that enrolled patients with newly diagnosed MHSPC from 248 academic and community centers across the US from March 1, 2013, to July 15, 2017. All patients in the intention-to-treat population who had available bone pain status were eligible and included in this secondary analysis.

Interventions: In the SWOG-1216 trial, patients were randomized (1:1) to receive either androgen deprivation therapy (ADT) with orteronel, 300 mg orally twice daily (experimental group), or ADT with bicalutamide, 50 mg orally daily (control group), until disease progression, unacceptable toxic effects, or patient withdrawal.

Main outcomes and measures: Overall survival was the primary end point; progression-free survival (PFS) and prostate-specific antigen (PSA) response were secondary end points. Cox proportional hazards regression models were used for both univariable and multivariable analyses adjusting for age, treatment type, Gleason score, disease volume, Zubrod performance status, and PSA level.

Results: Of the 1279 male study participants, 301 (23.5%) had baseline bone pain at MHSPC diagnosis and 896 (70.1%) did not. Bone pain status was unavailable in 82 patients (6.4%). The median age of the 1197 patients eligible and included in this secondary analysis was 67.6 years (IQR, 61.8-73.6 years). Compared with patients who did not experience bone pain, those with baseline bone pain were younger (median age, 66.0 [IQR, 60.1-73.4] years vs 68.2 [IQR, 62.4-73.7] years; P = .02) and had a higher incidence of high-volume disease (212 [70.4%] vs 373 [41.6%]; P < .001). After adjustment, bone pain was associated with shorter PFS and OS. At a median follow-up of 4.0 years (IQR, 2.5-5.4 years), patients with bone pain had median PFS of 1.3 years (95% CI, 1.1-1.7 years) vs 3.7 years (95% CI, 3.3-4.2 years) in patients without initial bone pain (adjusted hazard ratio [AHR], 1.46; 95% CI, 1.22-1.74; P < .001) and OS of 3.9 years (95% CI, 3.3-4.8 years) vs not reached (NR) (95% CI, 6.6 years to NR) in patients without initial bone pain (AHR, 1.66; 95% CI, 1.34-2.05; P < .001).

Conclusions and relevance: In this post hoc secondary analysis of the SWOG-1216 randomized clinical trial, patients with baseline bone pain at MHSPC diagnosis had worse survival outcomes than those without bone pain. These data suggest prioritizing these patients for enrollment in clinical trials, may aid patient counseling, and indicate that the inclusion of bone pain in prognostic models of MHSPC may be warranted.

Trial registration: ClinicalTrials.gov Identifier: NCT01809691.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Swami reported receiving personal fees from Astellas, Exelixis, Seattle Genetics, Imvax, Sanofi, AstraZeneca, and Gilead; grants from Janssen, Exelixis, and Astellas/Seattle Genetics; and personal fees from Pfizer outside the submitted work. Dr Gupta reported receiving grants from Bristol-Myers Squibb, Merck, EMD Sorono, Exelixis, Pfizer, Seattle Genetics, Moderna, Flare Therapeutics, Roche, Novartis, Tyra Biosciences, QED, and Gilead; personal fees from Bristol-Myers Squibb, Gilead, Seattle Genetics, and Astellas for speaking; and personal fees from Merck, Bristol-Myers Squibb, Gilead, Bayer, Sanofi, and Foundation Medicine for consulting outside the submitted work. Dr Hussain reported receiving grants (contracts with Northwestern University for clinical trials) from Arvinas, Bayer, and AstraZeneca during the conduct of the study; honoraria from Bayer, Novartis, Tango, and Convergent for serving on advisory boards; and honoraria for educational lectures or programs from MJH Life Sciences, Research to Practice, AstraZeneca, Academic CME, and Bayer outside the submitted work. Dr Dorff reported receiving consulting or advisory fees from Janssen, Bayer, and Sanofi outside the submitted work. Dr Lerner reported receiving consulting fees from Aura Biosciences, Protara, Verity, and Ferring; personal fees from BMS, AstraZeneca, UroGen, Pfizer, C2i Genomics, Surge Therapeutics, and Vaxxion for consulting; honoraria from Grand Rounds Urology and UroToday; grants from Aura Biosciences, Surge Therapeutics, Genentech, Ferring/FKD, Vaxxion, JBL, and QED Therapeutics for clinical trials, all outside the submitted work; and having a patent for The Cancer Genome Atlas subtype classifier for bladder cancer. Dr Agarwal reported receiving drug support from Takeda during the conduct of the study; receiving honoraria for consulting before May 2021 from Astellas, AstraZeneca, AVEO, Bayer, Bristol-Myers Squibb, Calithera, Clovis, Eisai, Eli Lilly, EMD Serono, Exelixis, Foundation Medicine, Genentech, Gilead, Janssen, Merck, MEI Pharma, Nektar, Novartis, Pfizer, Pharmacyclics, and Seattle Genetics; and receiving research funding during his lifetime (to his institution) from Arnivas, Astellas, AstraZeneca, Bavarian Nordic, Bayer, Bristol Meyers Squibb, Calithera, Celldex, Clovis, CRISPR Therapeutics, Eisai, Eli Lilly, EMD Serono, Exelixis, Genentech, Gilead, GlaxoSmithKline, Immunomedics, Janssen, Lava, Medivation, Merck, Nektar, Neoleukin, NewLink Genetics, Novartis, ORIC, Pfizer, Prometheus, Rexahn, Roche, Sanofi, Seattle Genetics, Takeda, and Tracon. No other disclosures were reported.

Figures

Figure.
Figure.. Kaplan-Meier Estimates of Overall Survival (OS) and Progression-Free Survival (PFS) by Bone Pain in the Overall Population
Dashed lines indicate the median time participants experienced OS or PFS; shading represents 95% CIs.
See this image and copyright information in PMC

References

    1. Agarwal N, Tangen CM, Hussain MHA, et al. . Orteronel for metastatic hormone-sensitive prostate cancer: a multicenter, randomized, open-label phase III trial (SWOG-1216). J Clin Oncol. 2022;40(28):3301-3309. doi:10.1200/JCO.21.02517 - DOI - PMC - PubMed
    1. Gebrael G, Fortuna GG, Sayegh N, Swami U, Agarwal N. Advances in the treatment of metastatic prostate cancer. Trends Cancer. 2023;9(10):840-854. doi:10.1016/j.trecan.2023.06.009 - DOI - PubMed
    1. Bienz M, Saad F. Management of bone metastases in prostate cancer: a review. Curr Opin Support Palliat Care. 2015;9(3):261-267. doi:10.1097/SPC.0000000000000157 - DOI - PubMed
    1. Halabi S, Vogelzang NJ, Kornblith AB, et al. . Pain predicts overall survival in men with metastatic castration-refractory prostate cancer. J Clin Oncol. 2008;26(15):2544-2549. doi:10.1200/JCO.2007.15.0367 - DOI - PubMed
    1. Oudard S, Banu E, Medioni J, et al. . What is the real impact of bone pain on survival in patients with metastatic hormone-refractory prostate cancer treated with docetaxel? BJU Int. 2009;103(12):1641-1646. doi:10.1111/j.1464-410X.2008.08283.x - DOI - PubMed

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