Early Chemo Linked to Improved PFS in High-Volume Metastatic Prostate Cancer

Patients with high-volume, castration-naïve metastatic prostate cancer may have superior progression-free survival (PFS) outcomes when treated with early docetaxel, according to findings published online in the European Journal of Cancer.

Using the Quality-adjusted Time Without Symptoms of disease and Toxicity of treatment (Q-TWiST) method, investigators also determined that the benefits associated with androgen deprivation therapy (ADT) plus docetaxel outweighed the risks associated with the treatment.

In 7-year follow-up results from the GETUG-AFU 15 trial conducted by the French Genito-Urinary Oncology Group, PFS was 35.05 months for patients assigned to ADT plus docetaxel compared with 27.08 months for ADT alone (P = .0078). Mean overall survival (OS) was not statistically different in the 2 arms (54.30 vs 51.26 months; P = 0.33).

“Early chemotherapy may provide significant Q-TWiST benefits in patients with [castration-naïve metastatic prostate cancer], especially those with high-volume disease, depending on the relative values associated with time spent with toxicity and after progression,” first author Patricia Marino PhD, Institut Paoli-Calmettes, Marseille, France, and coinvestigators wrote.

“The benefit of docetaxel was not observed for patients with low-volume disease. Reinforcing patient-physician communication about the treatment and its toxicity is important to help [in] making decisions, and further studies are needed to better quantify quality-adjusted survival,” added Marino et al.

From October 2004 through December 2008, researchers enrolled 193 patients in the ADT-alone arm and 192 in the ADT/docetaxel arm at 29 centers in France and 1 in Belgium. Among 385 total patients, 183 (48%) were classified as the high-volume subgroup and 202 patients (52%) were classified as low-volume.

As noted by Marino et al, ADT/docetaxel has become the first-line standard of care for patients with castration-naïve metastatic prostate cancer. However, some patients, especially those with low-volume disease, do not enjoy a survival benefit with the combination. Even for patients who do respond to treatment, physicians need a way to determine the ideal risk/benefit ratio because docetaxel is associated with well-known toxicities, including neutropenia, leukopenia, neurological toxic effects, and diarrhea.

Marino et al employed the. Q-TWIST to help physicians balance risk versus benefit. The method was specifically designed to quantify the risk/benefit trade-off by integrating these outcomes into a single outcome measure based on the assumption that patients with no symptoms have a better health-related quality of life than those with disease-related symptoms and/or treatment-related toxicity.

The Q-TWiST method separates OS time into 3 periods corresponding to different health states, usually the toxic phase of treatment (TOX), the time before progression without toxicity (TWIST), and the time after progression (PROG). These mean durations are then weighted to determine quality-adjusted survival times.

Investigators considered TWIST to be the patient’s best health state (twist = 1). By way of comparison, utox and uprog reflected the value of time spent in TOX and PROG relative to the TWIST state.

Patients in the combination arm spent more time in TOX (1.26 vs 0 months; P <.0001). Only chemotherapy-related toxicity was recorded for this analysis, so patients in the combination arm also spent significantly more time in TWiST compared with those assigned to ADT alone (33.79 vs 27.08 months; P = .0248) but less time in PROG (19.25 vs 24.18 months; P = .0394).

Q-TWiST duration was longer in the combination arm when u_twist = 1, u_tox = 0.5, and u_prog = 0.5, but the difference was not statistically significant (44.05 vs 39.17 months; P = .0819).

Sensitivity analysis showed that ADT/docetaxel was superior for all combinations of u_tox and u_prog, and all advantages associated with the treatment combination were found to be statistically significant. Investigators concluded that whatever the value of u_tox, the difference between Q-TWiST significantly favored ADT/docetaxel at all values of uprog lower than 0.4.

Marino P, Sfumato P, Joly F, et al. 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. Eur J Cancer. 2017;84:27-33. doi:10.1016/j.ejca.2017.07.008.