Efficacy and safety of the combination of paclitaxel and platinum in advanced thymic carcinoma.
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ABSTRACT:
SUBMITTER: Xu JP
PROVIDER: S-EPMC4773309 | biostudies-other | 2016 Mar
REPOSITORIES: biostudies-other
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Project description:Hepatocellular carcinoma (HCC) is one of the most common leading causes of cancer death worldwide. As most patients are diagnosed with advanced disease, systemic therapy remains the backbone of treatment. In recent years, we have witnessed the transformation of advanced HCC treatment landscapes from single-agent targeted therapies to immunotherapy combinations, with atezolizumab plus bevacizumab becoming the new first-line standard of care with an increase in overall survival, progression-free survival, and objective response rate compared to sorafenib, and a positive impact on quality of life. Although the efficacy and safety of this combination have been confirmed regardless of ethnicity, age, and etiology, only a subgroup of patients seems to benefit the most from this treatment. Currently, predictive serum and tissue biomarkers to select patients who are most likely to respond to atezolizumab plus bevacizumab are lacking. Moreover, the optimal subsequent therapy for patients who progress on first-line atezolizumab plus bevacizumab remains unknown, clinical trials are ongoing, and real-world data are needed to determine the most effective treatment sequence. Importantly, careful evaluation of bleeding risk and preservation of adequate liver function are fundamental to improve patients' prognosis, especially when subsequent treatments are administered.
| S-EPMC10557510 | biostudies-literature
Project description:BackgroundThe current exploratory analysis was performed to evaluate the efficacy and safety of everolimus for treatment of human epidermal growth factor receptor 2-positive (HER2+) advanced breast cancer in the Asian subset of patients in the BOLERO-1 trial.MethodsPostmenopausal women with HER2+ advanced breast cancer, who had not received systemic therapy for advanced disease, were randomized 2:1 to receive everolimus or placebo, plus trastuzumab and paclitaxel. The two primary end points were investigator-assessed progression-free survival (PFS) in the full population and in the hormone receptor-negative (HR-) subpopulation. Secondary end points included assessment of the objective response rate, the clinical benefit rate, and safety.ResultsIn the Asian subset, median PFS was similar in the everolimus (n = 198) and placebo (n = 105) arms in the full analysis set (hazard ratio = 0.82 (95% CI 0.61-1.11)). In the HR- subpopulation, everolimus prolonged median PFS by 10.97 months vs placebo (25.46 vs 14.49 months; hazard ratio = 0.48 (95% CI 0.29-0.79)). In the everolimus arm of the Asian subset, the most common adverse events of any grade were stomatitis (62.2%), diarrhea (48.0%), rash (43.4%) and neutropenia (42.3%). Neutropenia (grade 3: 27.6%; grade 4: 4.6%) and decreased neutrophil count (grade 3: 11.2%; grade 4: 3.6%) were the most frequent grade 3/4 adverse events. Serious adverse events included pneumonia (5.1%), pneumonitis (3.1%), and interstitial lung disease (3.1%). There were three deaths (1.5%) during treatment in the everolimus arm vs none in the placebo arm.ConclusionsThe efficacy and safety of everolimus plus trastuzumab and paclitaxel as first-line treatment for HER2+ advanced breast cancer in the Asian subset was consistent with that reported previously in the overall population.Trial registrationClinicalTrials.gov, NCT00876395 . Registered on 2 April 2009.
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Project description:PurposeWe report efficacy and safety with extended follow-up, and exploratory biomarker analyses from the phase II CheckMate 275 trial to identify biomarkers of response to nivolumab in platinum-resistant metastatic or unresectable urothelial carcinoma (mUC).Patients and methodsPatients received nivolumab 3 mg/kg once every 2 weeks until disease progression, unacceptable toxicity, or other protocol-defined reasons. The primary endpoint was objective response rate (ORR) per blinded independent review committee (BIRC; using RECIST v1.1) in all treated patients and by tumor PD-L1 expression. Key secondary endpoints were progression-free survival (PFS) per BIRC using RECIST v1.1 and overall survival (OS) in all patients and by PD-L1 expression. Exploratory endpoints included safety and biomarker analyses of tumor mutational burden (TMB), PD-L1, and previously identified mutational signatures.ResultsOf 270 treated patients, 139 had evaluable TMB. With 33.7 months' minimum follow-up, ORR per BIRC, median PFS, and median OS [95% confidence interval (CI)] in all treated patients were 20.7% (16.1-26.1), 1.9 months (1.9-2.3), and 8.6 months (6.1-11.3), respectively. No new safety signals were identified. Higher TMB was associated (P < 0.05) with improved ORR [OR (95% CI): 2.13 (1.26-3.60)], PFS [HR: 0.75 (0.61-0.92)], and OS [HR: 0.73 (0.58-0.91)]. TMB combined with PD-L1 better predicted ORR, PFS, and OS than PD-L1 alone. Higher mutational signature 2 score was associated with better OS but did not improve the predictive value of TMB.ConclusionsThese results support the durable antitumor activity of nivolumab and suggest that TMB may enrich for better response in mUC. Future studies of TMB/PD-L1 as biomarkers for response to nivolumab in randomized trials are warranted.See related commentary by Swami et al., p. 5059.
| S-EPMC8166422 | biostudies-literature
Project description:BackgroundCurrently there is no standard therapy recommended for second-line treatment for thymic carcinoma. Our study compared multidrug chemotherapy, single-agent chemotherapy, and PD-1 inhibitors in patients diagnosed with advanced thymic carcinoma who had previous platinum-based chemotherapy at the clinic.MethodsThe study included patients with thymic carcinoma who failed first-line platinum-based chemotherapy. Kaplan-Meier methods were applied in the study for estimating the progression-free survival (PFS) and overall survival (OS) curves. Pearson chi-square or Fisher's exact chi-square test was adopted to make comparisons of the objective response rate (ORR) between treatment groups. Cox regression was used for the multivariate analyses in PFS and OS.ResultsAmong the 92 patients enrolled, multidrug chemotherapy was used in 51 (55.4%) patients for second-line therapy. Thirty-six patients (35.9%) received single-agent chemotherapy, and eight patients (8.7%) underwent PD-1 inhibitors. The multidrug chemotherapy group showed better efficacy than the other two groups, with an ORR of 35.3% (p = 0.006). The median PFS of multidrug chemotherapy, single-agent chemotherapy and PD-1 inhibitors were 5.0 months, 3.0 months, and 4.0 months, respectively (p = 0.008). Patients in the multidrug chemotherapy group also showed an advantage in OS in comparison with the other two treatment groups (p = 0.045), with a median OS of 30.4 months. Multivariate analysis showed that second-line treatment was independent factor for both PFS (p = 0.035) and OS (p = 0.037). Grade 3-4 AEs were mostly detected in patients receiving multidrug chemotherapy and were primarily hematologic. Treatment-related mortality was not found in any of the groups.ConclusionsMultidrug chemotherapy had a trend toward a more positive response rate and outcomes in longer survival time than single-agent chemotherapy and PD-1 inhibitors. Multidrug chemotherapy is a choice worth considering for second-line therapy in patients with thymic carcinoma if tolerable.
| S-EPMC9939196 | biostudies-literature
Project description:Background and aimsSystemic combinations have recently brought significant therapeutic benefits for advanced hepatocellular carcinoma (aHCC). To design the most effective combination regimens, a systematic review (PROSPERO ID: CRD42022321949) was conducted to evaluate the efficacy and safety of systemic combinations on aHCC.MethodsWe retrieved all the studies from PubMed, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), and China National Knowledge Infrastructure (CNKI) using the Medical Subject Headings (MeSH) terms until December 21, 2022. The effect indicators (hazard ratio [HR], relative risk [RR], and median) were pooled by a fixed- or random-effects model. A subgroup analysis was conducted according to types and specific therapies.ResultsIn total, 88 eligible studies were selected from 7249 potential records. Each kind of combination treatment (chemotherapy plus chemotherapy, targeted plus immune checkpoint inhibitor (ICI) therapy, targeted plus chemotherapy, and targeted plus targeted therapy) had a better objective response rate (ORR) in patients with aHCC, compared to the monotherapy mostly with sorafenib (RR: 1.57 [1.44-1.71]; I 2 = 30%). Of those, targeted plus ICI therapy showed better therapeutic efficiency in overall survival (median: 15.02 [12.67-17.38]), progression-free survival (median: 7.08 [6.42-7.74]), and ORR (RR: 1.81 [1.55-2.13]), compared to the monotherapy. Specifically, Atezo plus Beva showed all those benefits. Our pooled result showed all the combinations had increased ≥3 Grade treatment-related adverse events (TrAEs), with an RR of 1.25 [95% CI: 1.15-1.36], compared to the monotherapy.ConclusionThe systemic combinations, especially targeted plus ICI therapy, including Atezo plus Beva, significantly improve clinical outcomes but increase side effects in patients with aHCC. Future trials should concentrate on improvement in therapeutic efficiency and reduction of toxicity of targeted plus ICI therapy.Systematic review registrationhttps://www.crd.york.ac.uk/prospero, identifier CRD42022321949.
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Project description:BackgroundAlterations in hedgehog signaling are implicated in the pathogenesis of basal-cell carcinoma. Although most basal-cell carcinomas are treated surgically, no effective therapy exists for locally advanced or metastatic basal-cell carcinoma. A phase 1 study of vismodegib (GDC-0449), a first-in-class, small-molecule inhibitor of the hedgehog pathway, showed a 58% response rate among patients with advanced basal-cell carcinoma.MethodsIn this multicenter, international, two-cohort, nonrandomized study, we enrolled patients with metastatic basal-cell carcinoma and those with locally advanced basal-cell carcinoma who had inoperable disease or for whom surgery was inappropriate (because of multiple recurrences and a low likelihood of surgical cure, or substantial anticipated disfigurement). All patients received 150 mg of oral vismodegib daily. The primary end point was the independently assessed objective response rate; the primary hypotheses were that the response rate would be greater than 20% for patients with locally advanced basal-cell carcinoma and greater than 10% for those with metastatic basal-cell carcinoma.ResultsIn 33 patients with metastatic basal-cell carcinoma, the independently assessed response rate was 30% (95% confidence interval [CI], 16 to 48; P=0.001). In 63 patients with locally advanced basal-cell carcinoma, the independently assessed response rate was 43% (95% CI, 31 to 56; P<0.001), with complete responses in 13 patients (21%). The median duration of response was 7.6 months in both cohorts. Adverse events occurring in more than 30% of patients were muscle spasms, alopecia, dysgeusia (taste disturbance), weight loss, and fatigue. Serious adverse events were reported in 25% of patients; seven deaths due to adverse events were noted.ConclusionsVismodegib is associated with tumor responses in patients with locally advanced or metastatic basal-cell carcinoma. (Funded by Genentech; Erivance BCC ClinicalTrials.gov number, NCT00833417.).
| S-EPMC5278761 | biostudies-literature
Project description:BACKGROUND:Thymoma and thymic carcinoma are rare thymic epithelial tumors. We investigated the efficacy of first-line gemcitabine and cisplatin (GP) chemotherapy versus gemcitabine and cisplatin chemotherapy combined with the anti-angiogenic drug endostar (GP + E) in advanced thymoma and thymic carcinoma. METHODS:The records of 45 patients with invasive metastatic thymomas or thymic carcinomas treated with GP as first-line therapy between August 2008 and July 2017 at the Department of Respiratory Medicine, Peking University Cancer Hospital and Institute were retrospectively reviewed. RESULTS:Eighteen patients (75%) in the GP + E group achieved a partial response and six (25%) had stable disease. In GP only group, nine (42.8%) patients achieved a partial response, 11 (52.4%) had stable disease, and one (4.8%) had progressive disease. The GP + E group had a significantly higher overall response rate (75% vs. 42.9%; P = 0.028), and median progression-free survival (PFS) and overall survival (OS) of 19 and 76 months, respectively. In the GP only group, median PFS and OS were 16 and 29 months, respectively. PFS and OS were not significantly different between the groups. CONCLUSIONS:GP has moderate efficacy and could represent a suitable first-line therapy for thymic carcinoma and thymoma. Chemotherapy combined with endostar could improve the overall response rate, but did not prolong PFS or OS.
| S-EPMC6312837 | biostudies-other
Project description:Purpose Seribantumab is a fully human immunoglobulin G2 monoclonal antibody that binds to human epidermal growth factor receptor (HER) 3 (ErbB3), blocking heregulin (HRG) -mediated ErbB3 signaling and inducing ErbB3 receptor downregulation. This open-label randomized phase II study evaluated progression-free survival (PFS) with seribantumab in combination with once-per-week paclitaxel compared with paclitaxel alone in patients with platinum-resistant or -refractory ovarian cancer. A key secondary objective was to determine if any of five prespecified biomarkers predicted benefit from seribantumab. Patients and Methods Patients with platinum-resistant or -refractory epithelial ovarian, fallopian tube, or primary peritoneal cancer were randomly assigned at a ratio of two to one to receive seribantumab plus paclitaxel or paclitaxel alone. Patients underwent pretreatment core needle biopsy; archival tumor samples were also obtained to support biomarker analyses. Results A total of 223 patients were randomly assigned (seribantumab plus paclitaxel, n = 140; paclitaxel alone, n = 83). Median PFS in the unselected intent-to-treat population was 3.75 months with seribantumab plus paclitaxel compared with 3.68 months with paclitaxel alone (hazard ratio [HR], 1.027; 95% CI, 0.741 to 1.425; P = .864). Among patients whose tumors had detectable HRG mRNA and low HER2 (n = 57 [38%] of 151 with available biomarker data), increased treatment benefit was observed in those receiving seribantumab plus paclitaxel compared with paclitaxel alone (PFS HR, 0.37; 95% CI, 0.18 to 0.76; P = .007). The HR in patients not meeting these criteria was 1.80 (95% CI, 1.08 to 2.98; P = .023). Conclusion The addition of seribantumab to paclitaxel did not result in improved PFS in unselected patients. Exploratory analyses suggest that detectable HRG and low HER2, biomarkers that link directly to the mechanism of action of seribantumab, identified patients who might benefit from this combination. Future clinical trials are needed to validate this finding and should preselect for HRG expression and focus on cancers with low HER2 levels.
| S-EPMC5562430 | biostudies-literature
Project description:To evaluate the safety and efficacy of combining yttrium-90 radioembolization (Y90-RE) with immune checkpoint inhibitor therapy, consecutive advanced unresectable hepatocellular carcinoma (HCC) patients treated between 2016 and 2022 with atezolizumab/bevacizumab or nivolumab within three-months pre- and post-Y90-RE were retrospectively evaluated. Tumor response and treatment-related clinical/laboratory adverse events (AE) were assessed at 1 and 6 months, as well as differences in clinical and laboratory variables and median overall survival (OS) from initial treatment (whether it was Y90-RE or systemic therapy) between the two cohorts. A total of 19 patients (10 atezolizumab/bevacizumab; 9 nivolumab), comprising 84% males with median age 69 years, met the inclusion criteria. Compared to the atezolizumab/bevacizumab group, there were less males (100% vs. 67%; p = 0.02) and more ECOG ≥ 2 patients in the nivolumab group (0% vs. 33%; p = 0.02). Baseline characteristics or incidence of 6-month post-treatment any-grade AE (60% vs. 56%; p = 0.7), grade ≥ 3 AE (0% vs. 11%; p = 0.3), objective response (58% total, 60% vs. 56%; p = 0.7), and complete response (16% total; 10% vs. 22%; p = 0.8) were similar between the atezolizumab/bevacizumab and the nivolumab cohorts. Median OS was 12.9 months for the whole cohort, 16.4 months for nivolumab, and 10.7 months for atezolizumab/bevacizumab. Among patients with advanced unresectable HCC, the utilization of Y90-RE concurrently or within 90 days of nivolumab or atezolizumab/bevacizumab immunotherapy, appears to be well-tolerated and with a low incidence of severe AE.
| S-EPMC10742675 | biostudies-literature
Project description:BACKGROUND:Thymic carcinomas (TCs) are rare aggressive tumors with no standard first-line treatment. This study was conducted to determine the optimal chemotherapy regimen for advanced TC. METHODS:This retrospective study included 67 patients treated for stage IV TC in 2006-2015. The primary endpoints were the objective response rate (ORR) and progression-free survival (PFS) with different chemotherapy regimens. Multivariate Cox regression analysis was used to identify factors associated with PFS, including metastatic status, radiotherapy post-chemotherapy, primary lesion resection before chemotherapy, and chemotherapy regimen. RESULTS:A total of 36 patients received a paclitaxel-platinum regimen, 31 received a gemcitabine-platinum regimen, 14 underwent primary lesion resection, and 33 underwent radiotherapy. ORR was 31% (11/36) and 29% (9/31) in the paclitaxel-platinum and gemcitabine-platinum groups, respectively (P = 0.890). Median PFS, one-year PFS rate, and two-year PFS rate were 7.0 months, 26%, and 6% with paclitaxel-platinum treatment and 12 months, 48%, and 24% with gemcitabine-platinum treatment (log-rank P = 0.030). Median PFS, one-year PFS rate, and two-year PFS rate were 18.0 months, 57%, and 33% with surgical resection and 7.3 months, 31%, and 7% without resection (log-rank P = 0.030). Median PFS, one-year PFS rate, and two-year PFS rate were 13.0 months, 52%, and 20% with radiotherapy and 4.3 months, 22%, and 7% without radiotherapy (log-rank P = 0.001). In multivariate analysis, metastatic status (hazard ratio [HR], 0.33, P = 0.004), surgical resection (HR, 0.32; P = 0.004), and radiotherapy (HR, 0.32; P < 0.001) were associated with superior PFS. CONCLUSIONS:Both gemcitabine-platinum and paclitaxel-platinum regimens were efficacious for advanced TC. Primary lesion resection and radiotherapy may also benefit selected patients.
| S-EPMC6825903 | biostudies-other