Bevacizumab plus chemotherapy continued beyond progression in patients with type II endometrial cancer previously treated with bevacizumab plus chemotherapy: A case report.
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ABSTRACT:
SUBMITTER: Sato E
PROVIDER: S-EPMC5530304 | biostudies-other | 2017 Sep
REPOSITORIES: biostudies-other
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Project description:Aims: This study aimed to evaluate the cost-effectiveness of lenvatinib plus pembrolizumab (LP) vs. chemotherapy for patients with previously treated mismatch repair proficient advanced endometrial cancer in China. Methods: A lifetime of partitioned survival Markov was used to evaluate the overall lifetime, total costs, quality adjusted life years (QALYs), and incremental cost effectiveness ratio (ICER) across a 10-years time horizon in the study 309-KEYNOTE-775 clinical trial. Direct costs and utility values were gathered from available literature. The willingness to pay (WTP) was defined at $37,663.26 per QALY. Sensitivity analyses were carried out to determine the model's uncertainty. Results: According to the baseline analysis, the LP group gained 4.02 total life years and 3.13 QALYs for $93,496.69, whereas the chemotherapy group gained 2.86 total life years and 2.24 QALYs for $30,578.04. LP versus chemotherapy resulted in an incremental cost of $62,918.65, with an ICER of $70,962.09/QALY, which was higher than China's WTP threshold ($37,663.26/QALY). The ICERs were most sensitive to the cost of pembrolizumab and the cycle of LP delivered, according to the sensitivity analysis. However, changing the range of those parameters has no influence on the model's results. Conclusion: Our present analysis suggests that LP treatment is not cost-effective for patients with previously treated mismatch repair proficient advanced endometrial cancer. However, LP treatment may be a cost-effective treatment option if the price is reduced.
| S-EPMC9561308 | biostudies-literature
Project description:BackgroundAMP-activated protein kinase (AMPK) has a central role in cellular energy sensing and is activated in preclinical tumour models following anti-vascular endothelial growth factor (VEGF) therapy. The possible predictive or prognostic role of AMPK status in cancer patients treated with anti-VEGF drugs has not been investigated so far.MethodsExpression of components of the AMPK pathway including phosphorylated AMPK (pAMPK), phosphorylated acetyl-Coa carboxylase (pACC) and liver kinase B1 (LKB1) was investigated by immunohistochemistry in 48 colorectal cancers treated with FOLFIRI plus bevacizumab. Correlation between pAMPK and pACC and associations between the AMPK pathway scores and clinico-pathological characteristics were assessed. Overall survival (OS) was estimated through Kaplan-Meier method, whereas hazard ratios were computed to identify prognostic factors.ResultsFourteen patients (29.2%) were included in the pAMPK-negative group (score ?5), whereas 34 patients (70.8%) were included in the pAMPK-positive group (score >5). The Spearman's coefficient for the correlation between pAMPK and pACC scores in primary tumour samples was 0.514 (P=0.0002). Low pAMPK levels were associated with worse OS (P-value 0.0002) but not with PFS, whereas low pACC levels were associated both with worse OS and PFS (P-value 0.0007 and 0.01, respectively).ConclusionsOur findings suggest that high tissue AMPK activation is a prognostic biomarker in this cohort of metastatic colorectal cancer patients.
| S-EPMC4090737 | biostudies-literature
Project description:BackgroundContinuation of bevacizumab plus second-line chemotherapy has significantly improved overall and progression-free survival in patients with metastatic colorectal cancer (mCRC). However, the cost-effectiveness of such high cost therapy is still uncertain in China; so this analysis was performed to evaluate the cost-effectiveness of these treatment options from the Chinese health care system perspective.MethodsA cost-effectiveness analysis was conducted using data from the ML18147 trial (ClinicalTrials.gov identifier NCT00700102) by modeling a partitioned survival model. Main evaluation indicators were quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio (ICER) with a willingness to pay (WTP) threshold of $38,201 per QALY. One-way and probabilistic sensitivity analyses were conducted to assess the robustness and stability of the model. Subgroup and scenario analyses were also performed to make our study more relevant.ResultsBevacizumab plus chemotherapy increased 0.12 QALYs and an incremental cost of $22,761.62 compared with chemotherapy, resulting in an ICER of $188,904.09 per QALY. The model was most sensitive to the utility of progression-free survival and the cost of bevacizumab. Compared with chemotherapy, bevacizumab plus chemotherapy had a 0% cost-effectiveness probability, and no cost-effectiveness in subgroups at the WTP threshold of $38,201 per QALY. The scenario analysis found that bevacizumab biosimilar gained an ICER of $126,397.38 per QALY when assuming the cost of drugs was calculated at the most affordable price.ConclusionsAt the WTP threshold of $38,201 per QALY, continuation of bevacizumab plus chemotherapy is unlikely considered cost-effective for patients after first progression of mCRC.
| S-EPMC10807607 | biostudies-literature
Project description:BackgroundBevacizumab improves outcome for most recurrent glioblastoma patients, but the duration of benefit is limited and survival after initial bevacizumab progression is poor. We evaluated bevacizumab continuation beyond initial progression among recurrent glioblastoma patients as it is a common, yet unsupported practice in some countries.MethodsWe analysed outcome among all patients (n=99) who received subsequent therapy after progression on one of five consecutive, single-arm, phase II clinical trials evaluating bevacizumab regimens for recurrent glioblastoma. Of note, the five trials contained similar eligibility, treatment and assessment criteria, and achieved comparable outcome.ResultsThe median overall survival (OS) and OS at 6 months for patients who continued bevacizumab therapy (n=55) were 5.9 months (95% confidence interval (CI): 4.4, 7.6) and 49.2% (95% CI: 35.2, 61.8), compared with 4.0 months (95% CI: 2.1, 5.4) and 29.5% (95% CI: 17.0, 43.2) for patients treated with a non-bevacizumab regimen (n=44; P=0.014). Bevacizumab continuation was an independent predictor of improved OS (hazard ratio=0.64; P=0.04).ConclusionThe results of our retrospective pooled analysis suggest that bevacizumab continuation beyond initial progression modestly improves survival compared with available non-bevacizumab therapy for recurrent glioblastoma patients require evaluation in an appropriately randomised, prospective trial.
| S-EPMC3493761 | biostudies-literature
Project description:Panitumumab and bevacizumab have been widely used in combination with chemotherapy for patients with wild type RAS metastatic colorectal cancer (mCRC). Whether panitumumab or bevacizumab was the optimal option remained controversial. Thus, we conducted a meta-anaylsis to evaluate chemotherapy plus panitumumab (C?+?P) versus chemotherapy plus bevacizumab (C?+?B) in wild type RAS mCRC. Electronic databases including PubMed, Embase, and Web of Science, Cochrane Library, ClinicalTrials.gov, were searched. This meta-analysis estimated the progression-free survival (PFS), overall survival (OS), overall response rate (ORR) and adverse events (AEs). Three randomized controlled trials with a total number of 577 patients were included. In wild type RAS population, PFS [hazard ratio (HR)?=?0.96; 95% confidence interval (CI), 0.76 to 1.15] and OS (HR?=?0.90; 95% CI, 0.54 to 1.27) and ORR [relative ratio (RR)?=?2.06; 95% CI, 0.86 to 4.90] appeared similar between the two treatments, the incidence of AEs slightly increased (RR?=?1.16; 95% CI 1.08 to 1.26). In conclusion, there was insufficient evidence to precisely conclude that combination treatment of C?+?P had an improved efficacy compared with C?+?B. Further large-scale and better-designed clinical trials are still needed to evaluate the combination treatment of C?+?P in patients with wild type RAS mCRC.
| S-EPMC5764984 | biostudies-literature
Project description:The activation of lymphocytes by gefitinib treatment has been described. In this phase II pilot trial, we explored the possible synergism between IL-2 and gefitinib for non-small cell lung cancer (NSCLC) treatment. From September, 2003, to November, 2006, 70 consecutive patients with advanced, progressive NSCLC, previously treated with chemotherapy, received oral gefitinib 250 mg daily. The first 39 patients received gefitinib alone (G group). The other 31 also received subcutaneous IL-2 (GIL-2 group): 1 MIU/m2 (Million International Unit/m2)twice a day on Days 1 and 2, once a day on Days 3, 4, 5 every week for four consecutive weeks with a four-week rest period. Median follow-up was 25.2 months. Grade 3-4 toxicity of gefitinib was represented by skin rash (7%), asthenia/anorexia (6%) and diarrhea (7%); patients treated with IL-2 showed grade 2-3 fever (46%), fatigue (21%) and arthralgia (13%). In the GIL-2 group and G-group, we respectively observed: an overall response rate of 16.1% (6.4% complete response) and 5.1% (only partial response); a disease control rate of 41.9% and 41%; a median time to progression of 3.5 (CI 95% = 3.2-3.8) and 4.1 (CI 95% = 2.6-5.7) months; a median overall survival of 20.1 (CI 95% = 5.1-35.1) and 6.9 (CI 95% = 4.9-8.9) months (p = 0.002); and an actuarial one-year survival rate of 54% and 30%. Skin toxicity (p < 0.001; HR = 0.29; CI 95% = 0.16-0.54) and use of IL-2 (p < 0.001; HR = 0.33; CI 95% = 0.18-0.60) were independently associated with improvement of survival. In this consecutive, non-randomized, series of advanced NSCLC patients, the use of IL-2 increased the efficacy of gefitinib.
| S-EPMC4276955 | biostudies-other
Project description:PurposeAtezolizumab, bevacizumab, carboplatin, and paclitaxel (ABCP) demonstrated survival benefit versus bevacizumab, carboplatin, and paclitaxel (BCP) in chemotherapy-naïve nonsquamous non-small-cell lung cancer (NSCLC). We present safety and patient-reported outcomes (PROs) to provide additional information on the relative impact of adding atezolizumab to chemotherapy with and without bevacizumab in nonsquamous NSCLC.MethodsPatients were randomly assigned to receive atezolizumab, carboplatin, and paclitaxel (ACP), ABCP, or BCP. Coprimary end points were overall survival and investigator-assessed progression-free survival. The incidence, nature, and severity of adverse events (AEs) were assessed. PROs, a secondary end point, were evaluated using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-Core 30 and EORTC QLQ-Lung Cancer 13.ResultsOverall, 400 (ACP), 393 (ABCP), and 394 (BCP) patients were safety evaluable (ie, intention-to-treat population that received one or more doses of any study treatment). More patients had grade 3/4 treatment-related AEs during the induction versus maintenance phase (ACP, 40.5% v 8.2%; ABCP, 48.6% v 21.2%; BCP, 44.7% v 11.1%). During induction, the incidence of serious AEs (SAEs) was 28.3%, 28.5%, and 26.4% in the ACP, ABCP, and BCP arms, respectively. During maintenance, SAE incidences were 20.0%, 26.3%, and 13.0%, respectively. Completion rates of the PRO questionnaires were > 88% at baseline and remained ≥ 70% throughout most study visits. Across arms, patients on average reported no clinically meaningful worsening of global health status or physical functioning scores through cycle 13. Patients across arms rated common symptoms with chemotherapy and immunotherapy similarly.ConclusionABCP seems tolerable and manageable versus ACP and BCP in first-line nonsquamous NSCLC. Treatment tolerability differed between induction and maintenance phases across treatment arms. PROs reflect a minimal treatment burden (eg, health-related quality of life, symptoms) with each regimen.
| S-EPMC7392741 | biostudies-literature
Project description:LESSONS LEARNED:RAS- or BRAF-mutated metastatic colorectal cancers (mCRCs) progressing after first-line treatment have a poor prognosis.European and U.S. guidelines include the multikinase inhibitor regorafenib as a standard option for second-line therapy and beyond, based on the results of the randomized phase III CORRECT trial demonstrating improvement in survival.Although stopped prematurely for failing to accrue, the PREVIUM trial, the first prospective interventional study exploring regorafenib as second-line treatment for patients with mCRC bearing RAS or BRAF mutations, failed to demonstrate clinical activity in the population analyzed. BACKGROUND:Patients with RAS- or BRAF-mutated (mut) metastatic colorectal cancer (mCRC) progressing on first-line bevacizumab plus 5-FU/irinotecan/oxaliplatin (FOLFOXIRI) have a poor prognosis. We aimed to assess the efficacy and safety of regorafenib in this population. METHODS:Regorafenib was administered daily for 3 weeks of each 4-week cycle until disease progression or other reason. The primary endpoint was 6-month progression-free survival (PFS). RESULTS:KRAS, NRAS, or BRAF was mutated in mCRC samples in 60%, 20%, and 13% of patients, respectively. Median time from initial diagnosis of metastases to the start of regorafenib and treatment duration was 13.8 months and 7 weeks, respectively. Reasons for discontinuation included disease progression (80%), investigator decision (13%), and adverse events (AEs; 7%). Seven patients (47%) required dose reduction, mostly for asthenia (43%). The most common regorafenib-related grade 3 AEs were asthenia (33%), dysphonia (13%), and hypertension (13%) (Table 1). There were no grade 4 toxicities. No patient was progression-free at 6 months. Median PFS, time to progression (TTP), and overall survival (OS) were 2.2, 2.0, and 3.3 months, respectively. CONCLUSION:Although stopped prematurely for failing to accrue, in the population analyzed, regorafenib failed to demonstrate clinical activity in KRAS- or BRAF-mutated mCRC with progression following first-line with FOLFOXIRI plus bevacizumab, although tolerability was acceptable. Our trial suggests that exploring regorafenib efficacy in an earlier line of therapy should not be undertaken without better population refinement.
| S-EPMC6291325 | biostudies-literature
Project description:BackgroundStage III or IVA endometrial cancer carries a significant risk of systemic and locoregional recurrence.MethodsIn this randomized phase 3 trial, we tested whether 6 months of platinum-based chemotherapy plus radiation therapy (chemoradiotherapy) is associated with longer relapse-free survival (primary end point) than six cycles of combination chemotherapy alone in patients with stage III or IVA endometrial carcinoma. Secondary end points included overall survival, acute and chronic toxic effects, and quality of life.ResultsOf the 813 patients enrolled, 736 were eligible and were included in the analysis of relapse-free survival; of those patients, 707 received the randomly assigned intervention (346 received chemoradiotherapy and 361 received chemotherapy only). The median follow-up period was 47 months. At 60 months, the Kaplan-Meier estimate of the percentage of patients alive and relapse-free was 59% (95% confidence interval [CI], 53 to 65) in the chemoradiotherapy group and 58% (95% CI, 53 to 64) in the chemotherapy-only group (hazard ratio, 0.90; 90% CI, 0.74 to 1.10). Chemoradiotherapy was associated with a lower 5-year incidence of vaginal recurrence (2% vs. 7%; hazard ratio, 0.36; 95% CI, 0.16 to 0.82) and pelvic and paraaortic lymph-node recurrence (11% vs. 20%; hazard ratio, 0.43; 95% CI, 0.28 to 0.66) than chemotherapy alone, but distant recurrence was more common in association with chemoradiotherapy (27% vs. 21%; hazard ratio, 1.36; 95% CI, 1.00 to 1.86). Grade 3, 4, or 5 adverse events were reported in 202 patients (58%) in the chemoradiotherapy group and 227 patients (63%) in the chemotherapy-only group.ConclusionsChemotherapy plus radiation was not associated with longer relapse-free survival than chemotherapy alone in patients with stage III or IVA endometrial carcinoma. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT00942357.).
| S-EPMC6948006 | biostudies-literature
Project description:The addition of bevacizumab to chemotherapy has demonstrated efficacy as a first-line treatment for non-small cell lung cancer (NSCLC). Whether this combination is effective as a salvage treatment for patients with NSCLC remains unclear. The present retrospective study was designed to compare the efficacy and safety of chemotherapy plus bevacizumab with chemotherapy alone as a third-line, or continuing, treatment for patients with NSCLC. Between January 2011 and June 2016, a total of 38 patients with stage IV NSCLC who had received chemotherapy plus bevacizumab subsequent to failure of ?2 prior regimens were matched with 38 patients who had received chemotherapy alone using propensity score matching from a dataset of 165 patients. The variables that were analyzed included age, sex, smoking history, histology, epithelial growth factor receptor mutation status, number of prior regimens and type of chemotherapy regimen. Univariate and multivariate analyses were used to evaluate the prognostic factors for survival outcomes and tumor response, and toxicity analyses were performed. The objective response rate (ORR) and disease control rate (DCR) were improved in patients who underwent chemotherapy-bevacizumab treatment compared with chemotherapy alone (ORR, 23.7 vs. 5.3%, P<0.001; DCR, 65.8 vs. 31.6%, P<0.001). Progression-free survival was prolonged in the chemotherapy-bevacizumab group compared with the chemotherapy-alone group (median, 3.9 vs. 2.2 months; HR, 0.54; 95% CI, 0.32-0.89, P=0.014). Incidence of ?grade 3 adverse events was low and similar across the groups. The combination of chemotherapy and bevacizumab is a potentially effective and safe alternative salvage treatment for patients with NSCLC who have not received bevacizumab treatment previously.
| S-EPMC5844063 | biostudies-literature