Q-TWiST analysis of patients with metastatic castrate naive prostate cancer treated by androgen deprivation therapy with or without docetaxel in the randomised phase III GETUG-AFU 15 trial

• Published in: European journal of cancer (1990) 2017-10, Vol.84, p.27-33
• Main Authors: Marino, P., Sfumato, P., Joly, F., Fizazi, K., Oudard, S., Culine, S., Habibian, M., Boher, J.-M., Gravis, G.
• Format: Article
• Language: English
• Subjects: Androgen Antagonists - adverse effects; Androgen Antagonists - therapeutic use; Antineoplastic Agents, Hormonal - adverse effects; Antineoplastic Agents, Hormonal - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Cancer; Castration; Chemotherapy; Clinical trials; Decision making; Deprivation; Disease Progression; Docetaxel; France; Humans; Kaplan-Meier Estimate; Male; Medical treatment; Metastases; Metastatic prostate cancer; Neoplasm Metastasis; Patients; Prostate cancer; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - mortality; Prostatic Neoplasms - pathology; Q-TWiST; Quality-Adjusted Life Years; Quality-adjusted survival; Risk Factors; Survival; Taxoids - adverse effects; Taxoids - therapeutic use; Time Factors; Toxic diseases; Toxicity; Tradeoffs; Treatment Outcome; Tumor Burden
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2017.07.008

Early chemotherapy has recently become a new standard of care for patients with metastatic castrate-naive prostate cancer (mCNPC). The survival benefit is evident in patients with high-volume disease, but less clear in those with low-volume disease. Here, we assessed the trade-offs between toxicity and survival using a Quality-adjusted Time Without Symptoms of disease and Toxicity of treatment (Q-TWiST) analysis. This analysis was performed from the data of the Genito-Urinary Oncology Group (GETUG)-AFU 15 phase III trial evaluating the benefits of docetaxel (D) combined with androgen deprivation therapy (ADT) versus ADT alone in 385 mCNPC patients. Overall survival was partitioned into three periods, namely toxic phase of treatment (TOX), time before progression without toxicity (TWIST), and progression (PROG). These health states were weighted according to patients' utility to determine quality-adjusted survival times. In threshold analyses, utility for TOX and PROG were varied from 0 to 1. A better quality-adjusted survival was found in the ADT + D arm when the utility for PROG and TOX states were ≤0.2 and ≥ 0.8, respectively. When the utility for PROG was 0.4 or more, ADT + D and ADT alone yielded similar quality-adjusted survival. When patients were stratified into high-volume versus low-volume disease, we found a significant Q-TWiST benefit in favour of the ADT + D arm only for high-volume patients when the utility for PROG was less than 0.35, while we found no benefit in low-volume disease patients, whatever the coefficients tested. Early docetaxel may provide significant quality-adjusted survival benefits for patients with mCNPC, especially those with high-volume disease, depending on the values assigned to the times spent in the toxicity phase and after PROG. The Q-TWiST methodology is a useful tool for decision-making regarding trade-offs between survival, PROG and toxicity. •We assessed quality-adjusted survival in patients with metastatic prostate cancer.•The quality-adjusted survival benefits are depending on the utilities of the toxicity and progression health states.•The quality-adjusted survival benefit of docetaxel was not observed for patients with low-volume disease.•The Quality-adjusted Time Without Symptoms or Toxicity (Q-TWiST) method is useful in cancer clinical trials.