Efficacy of Αtezolizumab-Βevacizumab in BCLC-C cirrhotic patients with hepatocellular carcinoma according to the type of disease progression, the type of BCLC-C and liver disease severity.

PURPOSE: The aim of our study was to evaluate, under real-life conditions, survival of patients with advanced HCC (BCLC-C), either initially presenting in that stage or migrating from BCLC-A to BCLC-C within 2 years after curative LR/RFA, treated either with Atezolizumab-Bevacizumab or TKIs. METHODS: Sixty-four cirrhotic patients with advanced HCC, who either initially presented as BCLC-C and were treated with Atezo-Bev (group A, N = 23) or TKIs (group B, N = 15) or who migrated from BCLC-A to BCLC-C stage within 2 years after LR/RFA and were either treated with Atezo-Bev (group C, N = 12) or TKIs (group D, N = 14), were retrospectively evaluated. RESULTS: The four groups were comparable for all baseline parameters (demographics/platelets/liver disease etiology/diabetes/varices/Child-Pugh stage/ALBI grade) except for CPT score and MELD-Na. Using Cox-regression analysis, we observed that survival of group C after systemic treatment onset was significantly higher compared to group A (HR 3.71, 1.20-11.46, p = 0.02) and presented a trend to statistical significance when compared to group D (HR 3.14, 0.95-10.35, p = 0.06), adjusted for liver disease severity scores. When all BCLC-C patients classified as such due to PS only were excluded from the study, a trend for the same survival benefit in group C was shown, even in the most difficult-to-treat population with extrahepatic disease or macrovascular invasion. CONCLUSION: Cirrhotic patients with advanced HCC initially diagnosed in BCLC-C, exhibit the worst survival irrespective of treatment schedule, whereas patients progressing to BCLC-C following disease recurrence after LR/RFA, seem to mostly benefit from Atezo-Bev, even patients with extrahepatic disease and/or macrovascular invasion. Liver disease severity seems to drive survival of these patients.

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 < 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.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.