Prognostic factors for regorafenib treatment in patients with refractory metastatic colorectal cancer: A real-life retrospective multi-center study

Regorafenib, an oral multikinase inhibitor, has improved survival in metastatic colorectal cancer (mCRC) patients who have progressed on standard therapies. Our study aimed to evaluate prognostic factors influencing regorafenib treatment and assess the optimal dosing regimen in a real-life setting. We retrospectively analysed 263 patients with mCRC from multiple medical oncology clinics in Turkey. Treatment responses and prognostic factors for survival were evaluated using univariate and multivariate analysis. Of the patients, 120 were male, and 143 were female; 28.9% of tumors were located in the rectum. RAS mutations were present in 3.0% of tumors, while BRAF, K-RAS, and N-RAS mutations were found in 3.0%, 29.7%, and 25.9% of tumor tissues, respectively. Dose escalation was preferred in 105 (39.9%) patients. The median treatment duration was 3.0 months, with an objective response rate (ORR) of 4.9%. Grade ≥ 3 treatment-related toxicity occurred in 133 patients, leading to discontinuation, interruption, and modification rates of 50.6%, 43.7%, and 79.0%, respectively. Median progression-free survival (PFS) and overall survival (OS) were 3.0 and 8.1 months, respectively. RAS/RAF mutation (hazard ratio [HR] 1.5, 95% confidence interval [CI] 1.1-2.3; P = 0.01), pretreatment carcinoembryonic antigen (CEA) levels (HR 1.6, 95% CI 1.1-2.3; P = 0.008), and toxicity-related treatment interruption or dose adjustment (HR 1.6, 95% CI 1.1-2.4; P = 0.01) were identified as independent prognostic factors for PFS. Dose escalation had no significant effect on PFS but was associated with improved OS (P < 0.001). Independent prognostic factors for OS were the initial TNM stage (HR 1.3, 95% CI 1.0-1.9; P = 0.04) and dose interruption/adjustment (HR 0.4, 95% CI 0.2-0.9; P = 0.03). Our findings demonstrate the efficacy and safety of regorafenib. Treatment line influences the response, with dose escalation being more favorable than adjustment or interruption, thus impacting survival

Atezolizumab in patients with metastatic urothelial carcinoma who have progressed after first-line chemotherapy: Results of real-life experience

Genitourinary Cancers Symposium of the American-Society-of-Clinical-Oncology (ASCO) -- FEB 13-15, 2020 -- San Francisco, CAWOS: 000529525900480[No abstract available]Amer Soc Clin Onco

Atezolizumab in Patients with Metastatic Urothelial Carcinoma Who Have Progressed After First-line Chemotherapy: Results of Real-life Experiences

Background: Atezolizumab (ATZ) has demonstrated antitumor activity and manageable safety in previous studies in patients with locally advanced or metastatic platinum resistant urothelial carcinoma. Objective: To compare the real-life experience and data of clinical trials on ATZ treatment in metastatic urothelial carcinoma. Design, setting, and participants: Patients with urothelial cancer treated with ATZ after progression on first-line chemotherapy from an expanded access program were retrospectively studied. Data of patients were obtained from their files and hospital records. Safety was evaluated for patients treated with at least one cycle of ATZ. Outcome measurements and statistical analysis: The primary endpoint was objective response rate (ORR). The secondary endpoints are overall survival (OS), progression-free survival (PFS), duration of response, and safety profile of patients. Kaplan-Meier methods were used to calculate median follow-up and estimate PFS and OS. Results and limitations: Data of 115 enrolled patients were analyzed. Most of the patients (92.3%, n = 106) had received chemotherapy regimen only once prior to ATZ. The median follow-up duration was 23.5 mo. The complete response rate, partial response rate, and ORR were 8.7% (n = 10), 20.0% (n = 23), and 28.7% (n = 33), respectively. The median duration of response was 20.4 mo (95% confidence interval [CI], 6.47-28.8). Of the 33 patients who responded to treatment, 60% (n = 20) had an ongoing response at the time of the analysis. PFS and OS with ATZ were 3.8 mo (95% CI, 2.25-5.49) and 9.8 mo (95% CI, 6.7-12.9), respectively. All-cause and any-grade adverse events were observed in 113 (98%) patients. Of the patients, 64% experienced a treatment-related adverse event of any grade and 24 (21.2%) had a grade 3-4 treatment-related adverse event. Limitations of the study included its retrospective design, and determination of treat-ment response based on clinical notes and local radiographic studies. Conclusions: In these real-life data, ATZ was effective and well tolerated in patients with metastatic urothelial carcinoma who have progressed with platinum-based first-line chemotherapy. ATZ is an effective and tolerable treatment for patients with locally advanced or metastatic platinum-resistant urothelial carcinoma in our study, similar to previously reported trials. Patient summary: Atezolizumab is effective and well-tolerated in patients with meta-static urothelial cancer who progressed with first-line chemotherapy, consistent with the outcomes of the previous clinical trials in this setting. (c) 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved

Experience from Turkish centers participating in the Early Access Program (EAP): Preliminary real-world safety data of nivolumab (nivo) combined with ipilimumab (ipi) in pre-treated advanced melanoma patients

Objective: We aimed to evaluate the safety of nivolumab + ipilimumab (nivo + ipi) in advanced melanoma patients who had relapsed after ≥1 line of systemic treatment in a real-world setting. Methods: Adult patients with advanced melanoma who had progressed after ≥1 line of systemic treatment were eligible for nivo 1 mg/kg + ipi 3 mg/kg Q3W × 4, followed by nivo 3 mg/kg Q2W until progression, or unacceptable toxicity for up to 24 months in the Early Access Program (EAP) in Turkey. Treatment-related adverse events (TRAEs) were recorded and analyzed. Results: Forty patients who received at least one dose of nivo + ipi were included. Median number of doses (Nivo + ipi and nivo alone) were 4 with a median follow-up of 19 weeks. Thirty patients (75%) were alive and 24 patients (60%) were on treatment. TRAEs of any grade and grade 3–4 occurred in 53% and 20% of the patients, respectively. One patient died due to TRAEs (colitis and diarrhea) after the second dose of nivo + ipi. Median times to onset and resolution of TRAEs were 6 and 3 weeks, respectively. Eleven patients (28%) discontinued treatment for reasons other than TRAEs. TRAEs of any grade led to discontinuation in 5 patients (13%). Most of the TRAEs were reversible when managed with available guidelines. Discussion: Safety profile of N + I was found to be consistent with early reports. Increased experience with the management of TRAEs of immunotherapies, short follow-up and ≥2 line real-world setting may account for lower TRAEs rates. Long-term follow is needed. Keywords: Nivolumab, Ipilimumab, Immunotherapy, Melanom

Real-Life Analysis of Efficacy and Safety of Everolimus Plus Exemestane in Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor-2-Negative Metastatic Breast Cancer Patients: A Turkish Oncology Group (TOG) Study

© 2021 Taylor & Francis Group, LLC.Purpose: This study evaluated the efficacy and safety of everolimus (EVE) plus exemestane (EXE) in hormone-receptor positive (HR+), human epidermal growth factor receptor-2-negative (HER2−) metastatic breast cancer (MBC) patients in real-life settings. Methods: Overall, 204 HR+, HER2− MBC patients treated with EVE + EXE after progressing following prior endocrine treatment were included. Overall survival (OS) and progression-free survival (PFS) and safety data were analyzed. Results: The objective response rate, median PFS, and median OS were 33.4%, 8.9 months, and 23.4 months, respectively. Multivariate analysis revealed that negative progesterone receptor status was a significant determinant of poor treatment response (p = 0.035) and PFS (p = 0.024). The presence of bone-only metastasis was associated with better treatment response (p = 0.002), PFS (p < 0.001), and OS (p = 0.001). Conclusion: We confirmed the favorable efficacy and safety profile of EVE + EXE for HR+, HER − MBC patients

Is there any prognostic significance in pleural involvement and/or effusion in patients with ALK-positive NSCLC?

PurposeAnaplastic lymphoma kinase (ALK) mutations occurs in approximately 3-5% of patients with non-small cell lung cancer (NSCLC). Pleural involvement/effusion is common in ALK-positive patients with NSCLC at baseline. The aim of the study was to evaluate the characteristics of ALK-positive patients who have Ple-I/E.MethodsIn this multicenter study, patients with ALK-positive NSCLC who have Ple-I/E were retrospectively analyzed. Clinical and demographic characteristics of the disease, response rates, median progression-free survival (PFS), and overall survival (OS) were evaluated in 362 ALK-positive patients with NSCLC.ResultsOf the patients, 198 (54.7%) were male. The median age at the time of diagnosis was 54 (range 21-85) years. All patients' histology was adenocarcinoma (100%). At baseline, 57 (15.7%) patients had Ple-I/E. There was no association between Ple-I/E and gender, lung metastasis, or distant lymphadenopathy (LAP) metastasis. The frequencies of liver, brain, and bone metastases were significantly higher in ALK-positive patients without Ple-I/E compared to those with Ple-I/E (respectively 18.2% vs 4.8%, p = 0.008; 19.1% vs 4.8%, p = 0.001; 20.6% vs 8.9%, p = 0.002). The median PFS was longer in ALK-positive patients who had Ple-I/E (18.7 vs 10.6 months, p = 0.017). Similarly, the median OS was longer in ALK-positive patients who had Ple-I/E (44.6 vs 22.6 months, p = 0.051).ConclusionBrain, liver, and bone metastases were lower in ALK-positive patients with Ple-I/E. Patients presented with Ple-I/E were prone to have better PFS and OS