Atezolizumab Versus Chemotherapy in Patients with Platinum-treated Locally Advanced or Metastatic Urothelial Carcinoma: A Long-term Overall Survival and Safety Update from the Phase 3 IMvigor211 Clinical Trial.

Atezolizumab is an anti-PD-L1 immune checkpoint inhibitor recommended for the treatment of locally advanced or metastatic urothelial carcinoma (mUC) after prior platinum-containing chemotherapy, regardless of PD-L1 status, among other treatment settings. We conducted a long-term follow-up to the exploratory analysis of overall survival (OS) and safety for the IMvigor211 intent-to-treat (ITT) population. Patients with mUC and disease progression during or following platinum-based chemotherapy were randomised 1:1 to receive atezolizumab 1200 mg or chemotherapy (vinflunine 320 mg/m2, paclitaxel 175 mg/m2, or docetaxel 75 mg/m2 according to investigator choice) intravenously every 3 wk. Although the primary analysis did not demonstrate statistically significant longer OS for patients receiving atezolizumab versus chemotherapy, updated OS showed long-term durable remission. With a median of 33 mo of follow-up, the 24-mo OS rate was 23% with atezolizumab and 13% with chemotherapy. Safety findings were consistent with the primary analysis, with no new signals detected. Chemotherapy-treated patients experienced more grade 3/4 treatment-related adverse events (AEs; 43% vs 22%) and more AEs leading to treatment discontinuation (18% vs 9%). Atezolizumab-treated patients experienced more AEs of special interest (35% vs 20%), which tended to be grade 1-2. Our findings support the use of atezolizumab in platinum-treated patients with mUC regardless of PD-L1 status. PATIENT SUMMARY: We report follow-up results from a study of an immunotherapy treatment, atezolizumab, in patients with bladder cancer who had already received platinum-containing chemotherapy. This analysis compared the effectiveness of atezolizumab with chemotherapy over 2.5 years after starting treatment. The results show that patients who received atezolizumab lived longer and had manageable side effects compared with patients who received chemotherapy. This trial is registered at ClinicalTrials.gov as NCT02302807.

Atezolizumab in Platinum-treated Locally Advanced or Metastatic Urothelial Carcinoma: Outcomes by Prior Number of Regimens.

BACKGROUND: Patients with metastatic urothelial carcinoma (mUC) who progress after platinum-based chemotherapy have had few treatment options and uniformly poor outcomes. Atezolizumab (anti-programmed death-ligand 1) was approved in the USA for cisplatin-ineligible and platinum-treated mUC based on IMvigor210, a phase 2, single-arm, two-cohort study. OBJECTIVE: To evaluate the efficacy and safety of atezolizumab by the number of prior lines of systemic therapy in patients with pretreated mUC. DESIGN, SETTING, AND PARTICIPANTS: IMvigor210 enrolled 315 patients with mUC with progression during or following platinum-based therapy at 70 international sites between May 2014 and November 2014. Key inclusion criteria included age ≥18 yr, creatinine clearance ≥30ml/min, and Eastern Cooperative Oncology Group performance status 0-1, with no limit on prior lines of treatment. INTERVENTION: Patients in this cohort received atezolizumab 1200mg intravenously every 3 wk until loss of clinical benefit. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Centrally assessed Response Evaluation Criteria In Solid Tumors v1.1 objective response rate (ORR), median duration of response, overall survival (OS), and adverse events were evaluated by prior treatment. Potential differences between subgroups were evaluated using log-rank (for OS) and chi-square (for ORR and adverse events frequencies) testing. RESULTS AND LIMITATIONS: Three hundred and ten patients were efficacy and safety evaluable (median follow-up, 21 mo). Objective responses and prolonged OS occurred across all prespecified subgroups; median duration of response was not reached in most subgroups. In patients without prior systemic mUC therapy (first-line subgroup), ORR was 25% (95% confidence interval: 14-38), and median OS was 9.6 mo (95% confidence interval: 5.9-15.8). No significant differences in efficacy or toxicity by therapy line were observed. CONCLUSIONS: Atezolizumab demonstrated comparable efficacy and safety in previously treated patients with mUC across all lines of therapy evaluated. PATIENT SUMMARY: We investigated effects of previous treatment in patients with metastatic urothelial carcinoma that progressed after platinum-based therapy. Atezolizumab was active and tolerable no matter how many treatment regimens patients had received. ClinicalTrials.gov, NCT02108652.

Home telehealth and hospital readmissions: a retrospective OASIS-C data analysis.

Technology holds potential to improve the quality of healthcare delivery. The use of remote patient monitoring, or telehealth (TH), has been widely adopted by many home care agencies to facilitate early identification of disease exacerbation, particularly for patients with chronic diseases such as heart failure. TH has been successfully used to improve symptom detection and potentially reduce rehospitalization rates. Quantifying program effectiveness through data analysis is a critical step for program improvement, resource allocation, and future strategic planning. Using the Outcome and Assessment Information Set-C database, a retrospective analysis was conducted examining 22 months of heart failure patient data from one home care agency in southern California. Seventy patients receiving TH were compared to patients who received usual home care nursing services. No major differences in baseline socio-demographics were found between the 2 groups. While receiving home healthcare services, the non-TH patients had a 21% all-cause hospital readmission rate, compared to the home TH patients with a 10% all-cause readmission rate. Statistical differences were found between groups on the variables of fall risk, vision, smoking, shortness of breath, the ability to bathe and take oral meds, along with having been discharged from a skilled nursing facility in the last 2 weeks. These results indicate that aggregate data analysis is useful in providing insight into program effectiveness. This study suggests TH programs have the potential to reduce the burden associated with rehospitalizations in the heart failure population.

Analysis of dermatologic events in vemurafenib-treated patients with melanoma.

BACKGROUND: Vemurafenib has been approved for the treatment of patients with advanced BRAF(V600E)-mutant melanoma. This report by the Vemurafenib Dermatology Working Group presents the characteristics of dermatologic adverse events (AEs) that occur in vemurafenib-treated patients, including cutaneous squamous cell carcinoma (cuSCC). METHODS: Dermatologic AEs were assessed from three ongoing trials of BRAF(V600E) mutation-positive advanced melanoma. Histologic central review and genetic characterization were completed for a subset of cuSCC lesions. RESULTS: A total of 520 patients received vemurafenib. The most commonly reported AEs were dermatologic AEs, occurring in 92%-95% of patients. Rash was the most common AE (64%-75% of patients), and the most common types were rash not otherwise specified, erythema, maculopapular rash, and folliculitis. Rash development did not appear to correlate with tumor response. Photosensitivity occurred in 35%-63% of patients, and palmar-plantar erythrodysesthesia (PPE) occurred in 8%-10% of patients. The severity of rash, photosensitivity, and PPE were mainly grade 1 or 2. In all, 19%-26% of patients developed cuSCC, mostly keratoacanthomas (KAs). The majority of patients with cuSCC continued therapy without dose reduction after resection. Genetic analysis of 29 cuSCC/KA samples demonstrated HRAS mutations in 41%. CONCLUSIONS: Dermatologic AEs associated with vemurafenib treatment in patients with melanoma were generally manageable with supportive care measures. Dose interruptions and/or reductions were required in <10% of patients.

Improved survival with vemurafenib in melanoma with BRAF V600E mutation.

BACKGROUND: Phase 1 and 2 clinical trials of the BRAF kinase inhibitor vemurafenib (PLX4032) have shown response rates of more than 50% in patients with metastatic melanoma with the BRAF V600E mutation. METHODS: We conducted a phase 3 randomized clinical trial comparing vemurafenib with dacarbazine in 675 patients with previously untreated, metastatic melanoma with the BRAF V600E mutation. Patients were randomly assigned to receive either vemurafenib (960 mg orally twice daily) or dacarbazine (1000 mg per square meter of body-surface area intravenously every 3 weeks). Coprimary end points were rates of overall and progression-free survival. Secondary end points included the response rate, response duration, and safety. A final analysis was planned after 196 deaths and an interim analysis after 98 deaths. RESULTS: At 6 months, overall survival was 84% (95% confidence interval [CI], 78 to 89) in the vemurafenib group and 64% (95% CI, 56 to 73) in the dacarbazine group. In the interim analysis for overall survival and final analysis for progression-free survival, vemurafenib was associated with a relative reduction of 63% in the risk of death and of 74% in the risk of either death or disease progression, as compared with dacarbazine (P<0.001 for both comparisons). After review of the interim analysis by an independent data and safety monitoring board, crossover from dacarbazine to vemurafenib was recommended. Response rates were 48% for vemurafenib and 5% for dacarbazine. Common adverse events associated with vemurafenib were arthralgia, rash, fatigue, alopecia, keratoacanthoma or squamous-cell carcinoma, photosensitivity, nausea, and diarrhea; 38% of patients required dose modification because of toxic effects. CONCLUSIONS: Vemurafenib produced improved rates of overall and progression-free survival in patients with previously untreated melanoma with the BRAF V600E mutation. (Funded by Hoffmann-La Roche; BRIM-3 ClinicalTrials.gov number, NCT01006980.).

Addition of bevacizumab to bolus fluorouracil and leucovorin in first-line metastatic colorectal cancer: results of a randomized phase II trial.

PURPOSE: Bevacizumab, a monoclonal antibody against vascular endothelial growth factor, increases survival when combined with irinotecan-based chemotherapy in first-line treatment of metastatic colorectal cancer (CRC). This randomized, phase II trial compared bevacizumab plus fluorouracil and leucovorin (FU/LV) versus placebo plus FU/LV as first-line therapy in patients considered nonoptimal candidates for first-line irinotecan. PATIENTS AND METHODS: Patients had metastatic CRC and one of the following characteristics: age > or = 65 years, Eastern Cooperative Oncology Group performance status 1 or 2, serum albumin < or = 3.5 g/dL, or prior abdominal/pelvic radiotherapy. Patients were randomly assigned to FU/LV/placebo (n = 105) or FU/LV/bevacizumab (n = 104). The primary end point was overall survival. Secondary end points were progression-free survival, response rate, response duration, and quality of life. Safety was also assessed. RESULTS: Median survival was 16.6 months for the FU/LV/bevacizumab group and 12.9 months for the FU/LV/placebo group (hazard ratio, 0.79; P = .16). Median progression-free survival was 9.2 months (FU/LV/bevacizumab) and 5.5 months (FU/LV/placebo); hazard ratio was 0.50; P = .0002. Response rates were 26.0% (FU/LV/bevacizumab) and 15.2% (FU/LV/placebo) (P = .055); duration of response was 9.2 months (FU/LV/bevacizumab) and 6.8 months (FU/LV/placebo); hazard ratio was 0.42; P = .088. Grade 3 hypertension was more common with bevacizumab treatment (16% v 3%) but was controlled with oral medication and did not cause study drug discontinuation. CONCLUSION: Addition of bevacizumab to FU/LV as first-line therapy in CRC patients who were not considered optimal candidates for first-line irinotecan treatment provided clinically significant patient benefit, including statistically significant improvement in progression-free survival.