Impact of progression at baseline and on-treatment progression events in three large prostate cancer trials.

There is a discussion about the optimal timing to initiate or switch treatment in metastatic castration-resistant prostate cancer (mCRPC). This post hoc analysis of 3 large trials for men with mCRPC examined the influence of the type of progression at initiation of first-line chemotherapy, as well as the type of progression during treatment, on treatment outcomes.

Data from the phase III studies VENICE (n = 1224), TAX327 (n = 1006) and FIRSTANA (n = 1168) were used as independent data sets. Type of progression was defined as follows: prostate-specific antigen (PSA) only (group 1), radiological (±PSA) (group 2) or pain (±PSA, ± radiological) progression (group 3). The impact of baseline type of progression on overall survival (OS) was evaluated in multivariate Cox regression analysis with backward elimination, stratified for the Eastern Cooperative Oncology Group performance score and treatment arm.

The median OS (arms combined) from treatment initiation in VENICE was 28.6, 26.3 and 16.9 months for G1, G2 and G3, respectively (hazard ratio: 1.14 [95% confidence interval {CI}: 0.92-1.41%] in G2 and 2.13 [95% CI: 1.75-2.59%] in G3 compared with G1). Multivariate analysis (arms combined) showed that pain progression at baseline was an independent predictor of poor OS. Similar findings were observed in the TAX327 and FIRSTANA data sets. During treatment, pain or radiological progression preceded PSA progression in ~55% of the patients. The retrospective characteristic of this study is a limitation.

The type of progression at baseline strongly predicts OS in men with mCRPC treated with first-line chemotherapy. During treatment, pain and/or radiological progression preceded PSA progression as the first progression event in ~55% of the patients. This finding has the prospect to be incorporated in clinical guidelines and to be practice changing because it implies the need for regular imaging and not to rely on PSA progression alone.

European journal of cancer (Oxford, England : 1990). 2019 Dec 11 [Epub ahead of print]

Debbie G Robbrecht, Nicolas Delanoy, Ian F Tannock, Bertrand Tombal, Mario Eisenberger, Karim Fizazi, Oliver Sartor, Florence Mercier, Stephane Oudard, Ronald de Wit

Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands. Electronic address: ., Medical Oncology, European Georges Pompidou Hospital, Paris, France. Electronic address: ., Medical Oncology, Princess Margaret Cancer Centre, Toronto, Ontario, CA, USA. Electronic address: ., Urology, Cliniques Universitaires St. Luc, Brussels, Belgium. Electronic address: ., Medical Oncology, Johns Hopkins Sidney Kimmel Cancer Center, Baltimore, USA. Electronic address: ., Department of Cancer Medicine, Gustave Roussy Institute, Villejuif, France. Electronic address: ., Medicine and Urology, Tulane Cancer Center, New Orleans, LA, USA. Electronic address: ., Stat Process, Sanofi, Paris, France. Electronic address: ., Medical Oncology, European Georges Pompidou Hospital, Paris, France. Electronic address: ., Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands. Electronic address: .

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