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A randomized trial involving patients with metastatic prostate cancer whose disease progressed after receipt of docetaxel and hormonal therapy showed that cabazitaxel was superior to an androgen-signaling–targeted agent in extending imaging-based progression-free survival, overall survival, and PSA response.

In the CARD study, cabazitaxel significantly improved radiographic progression-free survival and overall survival versus abiraterone or enzalutamide in patients with metastatic castration-resistant prostate cancer previously treated with docetaxel and the alternative androgen signalling-targeted inhibitor. Here, we report the quality-of-life outcomes from the CARD study. CARD was a randomised, multicentre, open-label, phase 4 study involving 62 clinical sites across 13 European countries. Patients (aged ≥18 years, Eastern Cooperative Oncology Group (ECOG) performance status ≤2) with confirmed metastatic castration-resistant prostate cancer were randomly assigned (1:1) by means of an interactive voice–web response system to receive cabazitaxel (25 mg/m2 intravenously every 3 weeks, 10 mg daily prednisone, and granulocyte colony-stimulating factor) versus abiraterone (1000 mg orally once daily plus 5 mg prednisone twice daily) or enzalutamide (160 mg orally daily). Stratification factors were ECOG performance status, time to disease progression on the previous androgen signalling-targeted inhibitor, and timing of the previous androgen signalling-targeted inhibitor. The primary endpoint was radiographic progression-free survival; here, we present more detailed analyses of pain (assessed using item 3 on the Brief Pain Inventory-Short Form [BPI-SF]) and symptomatic skeletal events, alongside preplanned patient-reported outcomes, assessed using the Functional Assessment of Cancer Therapy—Prostate (FACT-P) questionnaire and the EuroQoL—5 dimensions, 5 level scale (EQ-5D-5L). Efficacy analyses were done in the intention-to-treat population. Pain response was analysed in the intention-to-treat population with baseline and at least one post-baseline assessment of BPI-SF item 3, and patient-reported outcomes (PROs) were analysed in the intention-to-treat population with baseline and at least one post-baseline assessment of either FACT-P or EQ-5D-5L (PRO population). Analyses of skeletal-related events were also done in the intention-to-treat population. The CARD study is registered with ClinicalTrials.gov, NCT02485691, and is no longer enrolling. Between Nov 17, 2015, and Nov 28, 2018, of 303 patients screened, 255 were randomly assigned to cabazitaxel (n=129) or abiraterone or enzalutamide (n=126). Median follow-up was 9·2 months (IQR 5·6–13·1). Pain response was observed in 51 (46%) of 111 patients with cabazitaxel and 21 (19%) of 109 patients with abiraterone or enzalutamide (p<0·0001). Median time to pain progression was not estimable (NE; 95% CI NE–NE) with cabazitaxel and 8·5 months (4·9–NE) with abiraterone or enzalutamide (hazard ratio [HR] 0·55, 95% CI 0·32–0·97; log-rank p=0·035). Median time to symptomatic skeletal events was NE (95% CI 20·0–NE) with cabazitaxel and 16·7 months (10·8–NE) with abiraterone or enzalutamide (HR 0·59, 95% CI 0·35–1·01; log-rank p=0·050). Median time to FACT-P total score deterioration was 14·8 months (95% CI 6·3–NE) with cabazitaxel and 8·9 months (6·3–NE) with abiraterone or enzalutamide (HR 0·72, 95% CI 0·44–1·20; log-rank p=0·21). There was a significant treatment effect seen in changes from baseline in EQ-5D-5L utility index score in favour of cabazitaxel over abiraterone or enzalutamide (p=0·030) but no difference between treatment groups for change from baseline in EQ-5D-5L visual analogue scale (p=0·060). Since cabazitaxel improved pain response, time to pain progression, time to symptomatic skeletal events, and EQ-5D-5L utility index, clinicians and patients with metastatic castration-resistant prostate cancer can be reassured that cabazitaxel will not reduce quality of life when compared with treatment with a second androgen signalling-targeted inhibitor. Sanofi.

Background: In the PROSELICA phase III trial (NCT01308580), cabazitaxel 20 mg/m2 (CABA20) was non-inferior to cabazitaxel 25 mg/m2 (CABA25) in mCRPC patients previously treated with docetaxel (DOC). The present post hoc analysis evaluates how the type of progression at randomization affected outcomes. Methods: Progression type at randomization was defined as follows: PSA progression only (PSA-p; no radiological progression (RADIO-p), no pain), RADIO-p (±PSA-p, no pain), or pain progression (PAIN-p, ±PSA-p, ±RADIO-p). Relationships between progression type and overall survival (OS), radiological progression-free survival (rPFS), and PSA response (confirmed PSA decrease ≥ 50%) were analyzed. Results: All randomized patients (n = 1200) had received prior DOC, and 25.7% had received prior abiraterone or enzalutamide. Progression type at randomization was evaluable in 1075 patients (PSA-p = 24.4%, RADIO-p = 20.8%, PAIN-p = 54.8%). Pain progression was associated with clinical and biological features of aggressive disease. Median OS from CABA initiation or date of mCRPC diagnosis, all arms combined, was shorter in the PAIN-p group than in the RADIO-p or the PSA-p groups (12.0 versus 16.8 and 18.4 months, respectively, p < 0.001). In multivariate analysis, all arms combined, PAIN-p was an independent predictor of poor OS (HR = 1.44, p < 0.001). PSA response, rPFS, and OS were numerically higher with CABA25 versus CABA20 in patients with PAIN-p. Conclusions: This post hoc analysis of the PROSELICA phase III study shows that pain progression at initiation of CABA in mCRPC patients previously treated with DOC is associated with a poor prognosis. Disease progression should be carefully monitored, even in the absence of PSA rise.

BACKGROUNDPredictive biomarkers to guide chemotherapy decisions for metastatic castration-resistant prostate cancer (mCRPC) are lacking. Preclinical studies indicate that circulating tumor cell (CTC) studies of chromosomal instability (CTC-CIN) can predict taxane resistance.METHODSThe CARD trial randomized individuals with mCRPC progressing within a year of treatment with an androgen receptor pathway inhibitor (ARPI; enzalutamide or abiraterone acetate plus prednisolone/prednisone) to cabazitaxel or the alternative ARPI. As a preplanned biomarker analysis, CTCs were isolated from blood samples obtained at baseline, cycle 2, and the end of treatment. Associations between baseline CTC and CTC-CIN counts with imaging-based progression-free survival (ibPFS), overall survival (OS), time to prostate-specific antigen (PSA) progression, RECIST 1.1 objective response rate (ORR), and PSA50 response rate were assessed. RESULTSHigh baseline CTC-CIN counts significantly associated with worse OS after adjustment for confounding variables (median OS, 15.3 vs. 8.9 months; univariate HR, 2.16; 95% CI, 1.52-3.06; P < 0.001; multivariate HR, 1.56; 95% CI, 1.01-2.43; P = 0.047). Detectable CTC-CIN counts at baseline may predict a lack of ibPFS and OS benefit when comparing cabazitaxel with ARPI. CONCLUSIONThis preplanned analysis of biomarker data from the CARD trial confirms that CTC-CIN counts are a clinically useful prognostic and predictive biomarker of taxane resistance in mCRPC. Detectable CTC-CIN at baseline defines a patient subpopulation with unmet clinical needs in which alternative therapeutics should be tested.TRIAL REGISTRATIONClinicalTrials.gov number NCT02485691.FUNDINGFunded by Sanofi and Epic Sciences.

Aflibercept plus FOLFIRI prolongs overall survival (OS) in patients with metastatic colorectal cancer after the failure of oxaliplatin-containing therapy. QoLiTrap prospectively evaluated the quality of life (QoL) and effectiveness of this regimen in daily clinical practice, according to RAS status, sex, and prior targeted therapy, especially epidermal growth factor receptor inhibitors (EGFR-I). The primary endpoint was the percentage of patients whose EORTC QLQ-C30 global health status (GHS) improved or reduced by <5% from baseline during the first 12 weeks of therapy. Secondary endpoints included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. One thousand two hundred and seventy-seven patients were treated with aflibercept plus FOLFIRI and 872 were evaluable for QoL. GHS improved or decreased by <5% in 40.3% of cases. The ORR was 20.8%, the median PFS was 7.8 months (95% confidence interval (CI), 7.3–8.3), and the median OS was 14.4 months (95% CI, 13.1–18.1). After prior EGFR-I, the ORR was 23.7%, median PFS was 9.4 months (95% CI, 6.5–12.9), and median OS was 17.4 months (95% CI, 10.5–33.7). The safety profile was consistent with previously reported data. Aflibercept plus FOLFIRI given in daily practice maintained QoL in mCRC patients, was associated with a high objective tumor response, and retained its activity regardless of sex, RAS status, and prior EGFR-I therapy.