ABSTRACT
BACKGROUND: The studies IMvigor 210 cohort 2 and IMvigor211 evaluated the efficacy of atezolizumab in patients with locally advanced or metastatic urothelial cancer (mUC) upon progression to platinum-based chemotherapy worldwide. Yet, the real impact of this drug in specific geographical regions is unknown. MATERIALS AND METHODS: We combined individual-level data from the 131 patients recruited in Spain from IMvigor210 cohort 2 and IMvigor211 in a pooled analysis. Efficacy and safety outcomes were assessed in the overall study population and according to PD-L1 expression on tumour-infiltrating immune cells. RESULTS: Full data were available for 127 patients; 74 (58%) received atezolizumab and 53 (42%) chemotherapy. Atezolizumab patients had a numerically superior median overall survival although not reaching statistical significance (9.2 months vs 7.7 months). No statistically significant differences between arms were observed in overall response rates (20.3% vs 37.0%) or progression-free survival (2.1 months vs 5.3 months). Nonetheless, median duration of response was superior for the immunotherapy arm (non-reached vs 6.4 months; p = 0.005). Additionally, among the responders, the 12-month survival rates seemed to favour atezolizumab (66.7% vs 19.9%). When efficacy was analyzed based on PD-L1 expression status, no significant differences were found. Treatment-related adverse events of any grade occurred more frequently in the chemotherapy arm [46/57 (81%) vs 44/74 (59%)]. CONCLUSION: Patients who achieved an objective response on atezolizumab presented a longer median duration of response and numerically superior 12 month survival rates when compared with chemotherapy responders along with a more favorable safety profile. PD-L1 expression did not discriminate patients who might benefit from atezolizumab.
Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Antineoplastic Agents/therapeutic use , Carcinoma, Transitional Cell/drug therapy , Ureteral Neoplasms/drug therapy , Urethral Neoplasms/drug therapy , Urinary Bladder Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal, Humanized/adverse effects , Antineoplastic Agents/adverse effects , B7-H1 Antigen/metabolism , Carcinoma, Transitional Cell/metabolism , Carcinoma, Transitional Cell/mortality , Carcinoma, Transitional Cell/secondary , Cohort Studies , Female , Humans , Lymphocytes, Tumor-Infiltrating/metabolism , Male , Middle Aged , Progression-Free Survival , Spain , Survival Rate , Treatment Outcome , Ureteral Neoplasms/metabolism , Ureteral Neoplasms/mortality , Ureteral Neoplasms/pathology , Urethral Neoplasms/metabolism , Urethral Neoplasms/mortality , Urethral Neoplasms/pathology , Urinary Bladder Neoplasms/metabolism , Urinary Bladder Neoplasms/mortality , Urinary Bladder Neoplasms/pathologyABSTRACT
Neuroendocrine neoplasms (NENs) are considered a heterogeneous and rare entity. Its natural history is influenced by multiple clinicopathological characteristics, which guide the management of these patients. The development of molecular biology reveals that the PI3K-AKT-mTOR pathway plays a relevant role in tumorigenesis and progression of NENs. Mammalian target of rapamycin (mTOR) inhibitors, targeted agents that block this pathway, has improved outcomes in neuroendocrine tumors (NETs). Different therapeutic approaches, such as somatostatin analogs, chemotherapy, peptide receptor radionuclide therapy, and targeted agents, have shown benefits in the treatment of NETs. However, there are not any established prognostic or predictive biomarkers to select the best therapy option to individualize treatment. Although a relation between alterations in the PI3K-AKT-mTOR pathway and clinical outcomes has not been found, these anomalies are considered attractive biomarkers. Additional molecular analysis should be integrated in future clinical trials' design to identify potential predictive or prognostic biomarkers.