Cabazitaxel shows a consistently greater survival benefit compared to mitoxantrone in patients with mCRPC

Cel. Niniejsza analiza — wtórna do badania TROPIC — ma na celu ocenę czasu przeżycia całkowitego (overall survival, OS) po zastosowaniu kabazytakselu w podgrupach chorych, u których od początku nie uzyskano odpowiedzi na docetaksel (D) i odstawiono docetaksel D z powodu progresji choroby, oraz u chorych, u których uzyskano początkowo odpowiedź na D, lecz u których wystąpiła progresja nowotworu w czasie < 3 miesiące od ostatniej dawki D. U takich pacjentów uzyskanie korzyści z ponownego leczenia D jest mało prawdopodobne, dlatego też potrzebują oni nowych opcji terapeutycznych, takich jak kabazytaksel. Metody. Z 755 chorych z przerzutami raka gruczołu krokowego opornego na kastrację (metastatic castration-resistant prostate cancer, mCRPC), włączonych do badania TROPIC, u 362 (47,9%) nie zaobserwowano początkowej odpowiedzi na D i przerwano jego podawanie. U 155 (20,5%) — w ocenie badacza — obserwowano początkowo od­powiedź na leczenie D, lecz wystąpiła progresja w czasie < 3 miesiące od ostatniej dawki D, a 238 (31,5%) nie należało do żadnej z tych podgrup. Wszystkich pacjentów zrandomizowano do grup otrzymujących kabazytaksel w dawce 25 mg/m2 lub mitoksantron w dawce 12 mg/m2 podawanych dożylnie co 3 tygodnie oraz prednizon, przyjmowany doustnie w dawce 10 mg/dzień. Wyniki. W każdej z podgrup mediana czasu przeżycia całkowitego (OS) dla chorych otrzymujących kabazytaksel była zawsze większa niż w grupie otrzymującej mitoksantron. Największą korzyść wydłużenia czasu przeżycia całkowitego w porównaniu z grupą otrzymującą mitoksantron obserwowano w podgrupie chorych, u których początkowo zaob­serwowano odpowiedź na D, a następnie progresję w czasie < 3 miesiące od ostatniej dawki D {mediana 15,7 miesiąca w porównaniu z 11,6 miesiąca, współczynnik ryzyka HR (hazard ratio) 0,52; 95% przedział ufności CI (confidence interval) [0,35–0,76]}. Mediana czasu przeżycia wolnego od progresji była także znacząco lepsza w tej podgrupie w porównaniu z grupą otrzymującą mitoksantron (2,6 miesiąca w porównaniu z 1,4 miesiąca, HR 0,66 (0,48–0,91). Wniosek. Kabazytaksel w skojarzeniu z prednizonem wykazuje konsekwentnie korzystniejsze działanie na czas prze­życia w porównaniu z leczeniem mitoksantronem w skojarzeniu z prednizonem w każdej z podgrup, w szczególności u chorych, u których zaobserwowano odpowiedź na D zastosowany w pierwszej linii i u których doszło do progresji w czasie < 3 miesiące od ostatniej dawki D, a także u chorych bez początkowej odpowiedzi na D, którzy przerwali jego przyjmowanie w celu kontroli progresji choroby.Aim. This sub analysis of TROPIC study evaluates overall survival (OS) under cabazitaxel in patients who had no initial response to docetaxel (D ) and discontinued D for disease progression and those who initially responded to D but experienced disease progression < 3 months since last D dose. These patients are believed unlikely to benefit from D re-treatment and need new treatment options such as cabazitaxel. Methods. Of the 755 patients with metastatic castration-resistant prostate cancer (mCRPC) enrolled in TROPIC study, 362 (47.9%) had no initial response to D and discontinued it for disease progression, 155 (20.5%) had an initial response to D therapy according to investigator judgment but progressed < 3 months since last D dose and 238 (31.5%) did not belong to these two subgroups. All patients were randomized to receive cabazitaxel 25 mg/m2 or mitoxantrone 12 mg/m2 both every 3 weeks and prednisone 10 mg per os daily. Results. Median OS with cabazitaxel was consistently longer than with mitoxantrone in all subgroups. The highest survival benefit versus mitoxantrone was observed for patients who initially responded to D and then progres­sed < 3 months since last D dose (median OS 15.7 versus 11.6 months, Hazard ratio (HR) 0.52 [95% CI 0.35–0.76]). Median PFS was also significantly improved in the latter subgroup compared to mitoxantrone (2.6 versus 1.4 months, HR 0.66 [0.48–0.91]). Conclusion. Cabazitaxel plus prednisone consistently shows a greater survival benefit compared to mitoxantrone plus prednisone whatever the subgroup considered, including responders to first-line D who progressed < 3 months since last D and pts without initial response to D who discontinued it for disease progression

Pain Progression at Initiation of Cabazitaxel in Metastatic Castration-Resistant Prostate Cancer (mCRPC): A Post Hoc Analysis of the PROSELICA Study.

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 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

Cabazitaxel versus abiraterone or enzalutamide in metastatic castration-resistant prostate cancer: post hoc analysis of the CARD study excluding chemohormonal therapy for castrate-naive disease.

Background In the CARD study (NCT02485691), cabazitaxel significantly improved clinical outcomes versus abiraterone or enzalutamide in patients with metastatic castration-resistant prostate cancer previously treated with docetaxel and the alternative androgen-signalling-targeted inhibitor. However, some patients received docetaxel or the prior alternative androgen-signalling-targeted inhibitor in the metastatic hormone-sensitive (mHSPC) setting. Therefore, the CARD results cannot be directly translated to a Japanese population.Methods Patients (N = 255) received cabazitaxel (25 mg/m2 IV Q3W, prednisone, G-CSF) versus abiraterone (1000 mg PO, prednisone) or enzalutamide (160 mg PO) after prior docetaxel and progression ≤12 months on the alternative androgen-signalling-targeted inhibitor. Patients who received combination therapy for mHSPC were excluded (n = 33) as docetaxel is not approved in this setting in Japan.Results A total of 222 patients (median age 70 years) were included in this subanalysis. Median number of cycles was higher for cabazitaxel versus androgen-signalling-targeted inhibitors (7 versus 4). Clinical outcomes favoured cabazitaxel over abiraterone or enzalutamide including, radiographic progression-free survival (rPFS; median 8.2 versus 3.4 months; P < 0.0001), overall survival (OS; 13.9 versus 11.8 months; P = 0.0102), PFS (4.4 versus 2.7 months; P < 0.0001), confirmed prostate-specific antigen response (37.0 versus 14.4%; P = 0.0006) and objective tumour response (38.9 versus 11.4%; P = 0.0036). For cabazitaxel versus androgen-signalling-targeted inhibitor, grade ≥ 3 adverse events occurred in 55% versus 44% of patients, with adverse events leading to death on study in 2.7% versus 5.7%.Conclusions Cabazitaxel significantly improved outcomes including rPFS and OS versus abiraterone or enzalutamide and are reflective of the Japanese patient population. Cabazitaxel should be considered the preferred treatment option over abiraterone or enzalutamide in this setting

Real-World Evaluation of Quality of Life, Effectiveness, and Safety of Aflibercept Plus FOLFIRI in Patients with Metastatic Colorectal Cancer: The Prospective QoLiTrap Study.

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 &amp;lt;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 &amp;lt;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