The clinical impact of bone scan (BS) flare with enzalutamide (ENZA) in men with metastatic castration-resistant prostate cancer (mCRPC).
Armstrong, AJ; Al-Adhami, M; Lin, P; Parli, T; Sugg, J; Steinberg, JL; TOMBAL, BF; Sternberg, CN; De Bono, JS; Scher, HI; Beer, TM
Published in: Journal of Clinical Oncology
183 Background: Current PCWG3 guidelines for men with mCRPC define BS progression during therapy as requiring confirmation of new bone lesions that develop over time with additional new lesions. New unconfirmed BS lesions may reflect slow progression or a favorable osteoblastic reaction called a “BS flare” that can be misinterpreted as radiographic progression and lead to premature therapy discontinuation. The prevalence and clinical impact of BS flare is unknown for ENZA. Methods: We analyzed the association of BS flare with clinical outcomes and quality of life (QoL) in a retrospective analysis of two phase 3 trials of men with mCRPC treated with ENZA after (AFFIRM n = 1199) and before (PREVAIL n = 1717) docetaxel. Early and late BS flare was defined as new lesions on the first posttreatment BS (weeks 9-13) or subsequent BS, respectively, that were not confirmed to meet progression criteria on the next BS, while also requiring responding/stable PSA and soft-tissue disease. Results: Unconfirmed BS lesions were observed in 22% and 25% of stable/responding men receiving ENZA in AFFIRM and PREVAIL, respectively. Most BS flares were early, but late flares (week 17 or later) were seen in 2% and 13% of men, respectively. Unconfirmed BS lesions (early or late) had no impact on OS (HR 0.87; 95% CI 0.62-1.21) or rPFS (HR 0.91; 95% CI 0.58-1.44) in PREVAIL, but were associated with worse OS (HR 2.26; 95% CI 1.55-3.30) and rPFS (HR 1.73; 95% CI 1.33-2.26) in AFFIRM. Soft-tissue responses and PSA declines were more prominent in chemo-naïve men with unconfirmed BS lesions, which also had no impact on QoL or pain deterioration in either setting. Conclusions: BS flare occurred in ≈25% of responding men with mCRPC receiving ENZA and was not associated with adverse outcomes in chemo-naïve men. Our findings support the importance of avoiding premature treatment discontinuation in the presence of unconfirmed new BS lesions in the first 4 months of therapy. Worse outcomes associated with unconfirmed lesions in men post docetaxel illustrate the need for improved functional bone imaging in mCRPC and broader patient assessment to decide on treatment continuation. Clinical trial information: NCT00974311; NCT01212991.
