Efficacy and safety of anlotinib plus XELOX regimen as first-line therapy for mCRC: a single-arm, multicenter, phase II study (ALTER-C-001)
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SUBMITTER: Song B
PROVIDER: S-EPMC10505961 | biostudies-literature | 2023 Jan
REPOSITORIES: biostudies-literature
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Project description:BackgroundThere is no consensus on whether triplet regimen is better than doublet regimen in the first-line treatment of advanced gastric cancer (AGC). We aimed to compare the efficacy and safety of oxaliplatin plus capecitabine (XELOX) and epirubicin, oxaliplatin, plus capecitabine (EOX) regimens in treating AGC.MethodsThis phase III trial enrolled previously untreated patients with AGC who were randomly assigned to receive the XELOX or EOX regimen. The primary endpoint was non-inferiority in progression-free survival (PFS) for XELOX as compared with EOX on an intention-to-treat basis.ResultsBetween April 10, 2015 and August 20, 2020, 448 AGC patients were randomized to receive XELOX (n = 222) or EOX (n = 226). The median PFS (mPFS) was 5.0 months (95% confidence interval [CI] = 4.5-6.0 months) in the XELOX arm and 5.5 months (95% CI = 5.0-6.0 months) in the EOX arm (hazard ratio [HR] = 0.989, 95% CI = 0.812-1.203; Pnon-inferiority = 0.003). There was no significant difference in median overall survival (mOS) (12.0 vs. 12.0 months, P = 0.384) or objective response rate (37.4% vs. 45.1%, P = 0.291) between the two groups. In patients with poorly differentiated adenocarcinoma and liver metastasis, the EOX arm had a significantly longer mOS (P = 0.021) and a trend of longer mPFS (P = 0.073) than the XELOX arm. The rate of grade 3/4 adverse events (AEs) was 42.2% (90/213) in the XELOX arm and 72.5% (156/215) in the EOX arm (P = 0.001). The global health-related quality of life (QoL) score was significantly higher in the XELOX arm than in the EOX arm during chemotherapy.ConclusionsThis non-inferiority trial demonstrated that the doublet regimen was as effective as the triplet regimen and had a better safety profile and QoL as a first-line treatment for AGC patients. However, the triplet regimen might have a survival advantage in patients with poorly differentiated adenocarcinoma and liver metastasis.
| S-EPMC9017757 | biostudies-literature
Project description:BackgroundCurrently, the need for new therapeutic strategies involving programmed cell death protein-1 (PD-1) monoclonal antibodies in the second-line setting of small cell lung cancer (SCLC) is urgent. This study aimed to evaluate the efficacy and safety of anlotinib plus penpulimab as a second-line treatment for patients with SCLC who progressed after first-line platinum-based chemotherapy.MethodsThis study included the patients from Cohort 4 of a single-arm, open-label, multicenter, phase II clinical trial. A safety run-in phase was performed under anlotinib (10/12 mg quaque die [QD], days 1-14) plus penpulimab (200 mg intravenously [IV], day 1) in a 21-day cycle, followed by the formal trial in which the patients received anlotinib (12 mg QD, days 1-14) plus penpulimab (200 mg IV, day 1) in a 21-day cycle. The primary endpoint of the safety run-in phase was safety. The primary endpoint of the formal trial phase was the objective response rate (ORR).ResultsFrom April 28, 2020, to November 24, 2020, 21 patients were enrolled from 11 hospitals, including 2 in the safety run-in phase and 19 in the formal trial phase. In the formal trial phase, the ORR was 42.1% (8/19; 95% confidence interval [CI]: 17.7-66.6%). The median progression-free survival was 4.8 months (95% CI: 2.9-11.3 months), and the median overall survival was 13.0 months (95% CI: 4.6-not applicable [NA] months). The incidence of ≥grade 3 treatment-related adverse events (TRAEs) was 52.4% (11/21), and the incidence of treatment-related serious adverse events (AEs) was 28.6% (6/21). Two AE-related deaths occurred. The most common AEs were hypertension (57.1%, 12/21), hypothyroidism (42.9%, 9/21), and hypertriglyceridemia (38.1%, 8/21).ConclusionsIn patients with SCLC who progressed after first-line platinum-based chemotherapy, the second-line anlotinib plus penpulimab treatment demonstrates promising anti-cancer activity and a manageable safety profile, which warrants further investigation.Trial registrationNo. NCT04203719, https://clinicaltrials.gov/.
| S-EPMC11447333 | biostudies-literature
Project description:PurposeSimvastatin has demonstrated anti-tumor activity in preclinical studies via tumor cell senescence, apoptosis, and anti-angiogenesis. This phase II trial evaluated the efficacy and toxicity profile of conventional XELOX and bevacizumab chemotherapy plus simvastatin in metastatic colorectal cancer patients (MCRC).Materials and methodsPatients with MCRC received first-line XELOX in 3-week treatment cycles of intravenous oxaliplatin 130 mg/m2 plus bevacizumab 7.5 mg/kg (day 1), followed by oral capecitabine 1,000 mg/m2 twice daily (day 1-14). Simvastatin 80 mg tablets were taken orally once daily every day during the period of chemotherapy. The primary endpoint was progression-free survival (PFS). Secondary endpoints were response rate, duration of response, overall survival (OS), time to progression, and toxicity.ResultsFrom January 2014 to April 2015, 60 patients were enrolled and 55 patients were evaluable for tumor response. The median follow-up duration was 30.1 months (range, 28.5 to 31.7 months). The median PFS was 10.4 months (95% confidence interval [CI], 9.6 to 11.1). The median OS of all patients was 19.0 months (95% CI, 11.9 to 26.0). The disease-control rate and overall response rate were 88.3% (95% CI, 74 to 96) and 58.3% (95% CI, 44 to 77), respectively, by intent-to-treat protocol analysis. There was one complete response and 34 partial responses. One patient experienced grade 3 creatine kinase elevation and liver enzyme elevation.ConclusionBased on the current study, the addition of 80 mg simvastatin to XELOX and bevacizumab showed comparable clinical efficacy in patients with MCRC as first-line chemotherapy and did not increase toxicity.
| S-EPMC6639242 | biostudies-literature
Project description:BackgroundAnlotinib as a third-line or beyond therapy for extensive-stage small-cell lung cancer (ES-SCLC) was studied. This single-arm phase II trial was to investigate the value of anlotinib plus platinum-etoposide as first-line treatment in ES SCLC.MethodsThe primary endpoint was progression-free survival (PFS) and objective response rate (ORR). The secondary endpoints included overall survival (OS), disease control rate (DCR), time to progression (TTP), duration of remission (DoR), and safety. The subgroups of preset liver metastasis and brain metastasis were analyzed.ResultsIn 35 ES-SCLC patients, the median PFS, ORR, DCR, and OS were 8.02 months [95% confidence interval (CI): 6.90-9.66], 85.71% (95% CI: 69.74-95.19), 94.29% (95% CI: 80.84-99.30), and 15.87 months (95% CI: 10.38-18.89), respectively. The median PFS in the liver metastasis and brain metastasis subgroups was 7.33 months (95% CI: 4.76-9.69) and 7.34 months (95% CI: 5.68-9.20), respectively. The most common AEs with grade 3-4 were hand-foot syndrome (17%), granulocytosis (17%), stomatitis (14%), hypertriglyceridemia (11%), hypercholesterolemia (11%), as well as nausea and vomiting (11%), and no grade 5 AEs were recorded.ConclusionsAnlotinib combined with platinum-etoposide provided an effective and safe therapy for patients with ES-SCLC.
| S-EPMC9554443 | biostudies-literature
Project description:This multicohort phase II trial (ALTER-G-001; NCT05262335) aimed to assess the efficacy of first-line anlotinib plus chemotherapy for gastrointestinal (GI) cancer patients with unresectable liver metastases. Eligible patients with colorectal cancer (Cohort A) or noncolorectal and nonesophageal GI cancer (Cohort C) received six cycles of anlotinib plus standard chemotherapeutic regimens followed by anlotinib plus metronomic capecitabine as a maintenance therapy. Liver metastasectomy can be performed when liver metastases are converted to resectable lesions. The primary outcome was the investigator-confirmed objective response rate (ORR) in the intention-to-treat population. Among the 47 patients in Cohort A, the ORR was 40.4% (95% CI 26.4-55.7), including 1 with a complete response (CR) and 18 who achieved a partial response (PR). The median progression-free survival (PFS) was 8.7 months (95% CI 7.3-NE), and the median overall survival (OS) was not reached. In Cohort C, 14 of 44 patients achieved a PR, with an ORR of 31.8% (95% CI 18.6-47.6). The PFS and OS were 5.8 months (95% CI 4.8-6.5) and 11.4 months (95% CI 5.8-19.3), respectively. The liver metastasectomy rate in patients with liver-limited disease was 22.7% (5/22) in Cohort A and 6.7% (2/30) in Cohort C. For pancreatic cancer patients, the ORR of the efficacy-evaluable population was 36.0% (9/25), and those with liver-limited metastasis had better survival. Moreover, no new safety concerns emerged. In conclusion, an anlotinib-based first-line regimen demonstrated promising antitumor activity among GI cancer patients with unresectable liver metastases and led to liver metastasectomy in selected patients.
| S-EPMC11625826 | biostudies-literature
Project description:BackgroundNo standard maintenance treatment has been obtained to prolong the response duration of soft tissue sarcoma (STS) after first-line chemotherapy. In this study, we aimed to evaluate the efficacy and safety of anlotinib as a maintenance treatment after chemotherapy in STS.MethodsIn this multicentre, open-label, single-arm phase 2 trial, patients with advanced STS who achieved partial response or stable disease after first-line anthracycline-based chemotherapy were enrolled between April 2019 and January 2022. All patients received anlotinib as a maintenance treatment. The primary endpoint was progression-free survival (PFS) of anlotinib maintenance treatment. Other endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR) and safety. This study is registered with ClinicalTrials.gov, NCT03890068.FindingsAt the data cut-off date (August 8, 2022), 49 patients were enrolled, including 17 with liposarcoma (35%) and 15 with leiomyosarcoma (31%). After a median follow-up of 17.1 months (IQR 9.0-27.2), the median PFS from the beginning of maintenance treatment was 9.1 months (95% CI 5.7-12.5), and the median OS was not reached, and the 1-year OS rate for anlotinib maintenance treatment was 98.0%. The best ORR and DCR were 16% (8/49, 95% CI 7-30) and 94% (46/49, 95% CI 83-99), respectively. Most of the treatment-related adverse events were grade 1-2. Of the grade 3-4 adverse events, the most common were hypertension (10%) and hand-foot syndrome reaction (6%).InterpretationPostchemotherapy maintenance treatment with anlotinib exhibits promising efficacy and tolerable toxicity in patients with advanced STS.FundingChia Tai Tianqing Pharmaceutical Group Co., Ltd., the National Key Research and Development Program of China, and the National Natural Science Foundation of China.
| S-EPMC10520347 | biostudies-literature
Project description:ObjectivesClinical studies have shown that bevacizumab plus chemotherapy significantly improves efficacy in metastatic colorectal cancer (mCRC). This prospective study aims to investigate the efficacy and safety of changing second-line treatment to raltitrexed-based chemotherapy regimens plus bevacizumab in mCRC patients who have failed the first-line fluorouracil-based chemotherapy regimen with or without bevacizumab/cetuximab.MethodsThis is a prospective, open-label, multicenter, phase II clinical study. A total of 100 patients with mCRC after failure of the first-line fluorouracil-based chemotherapy regimen with or without bevacizumab/cetuximab were enrolled from November 2016 to October 2021, and received second-line raltitrexed-based chemotherapy regimen plus bevacizumab. Patients were treated for 6 cycles, and efficacy evaluation over stable disease were followed by maintenance treatment of bevacizumab and raltitrexed until disease progression or intolerable toxicity. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), safety, and toxicity.ResultsNinety-four patients were treated with SALIRI (raltitrexed + irinotecan) plus bevacizumab, and six patients with SALOX (raltitrexed + oxaliplatin) plus bevacizumab. Median PFS was 8.4 (95% CI: 6.2-11.0) months, including 8.2 (95% CI 6.2, 11.0) months in the SALIRI group and 11.6 (95% CI 3.1, NA) months in the SALOX group. Median OS was 17.6 (95% CI 15.2, 22.0) months in the SALIRI group and 17.1 (95% CI 4.1, NA) months in the SALOX group. ORR and DCR were 25.5% and 87.2% in the SALIRI group, and 33.3% and 83.3% in the SALOX group, respectively. A low incidence of grade 3-4 adverse events was observed.ConclusionsRaltitrexed-based chemotherapy regimens plus bevacizumab improved survival duration in mCRC patients with failed first-line therapy. Therefore, treatment with raltitrexed-based chemotherapy regimens plus bevacizumab could be a superior therapeutic option for second-line chemotherapy in mCRC (ClinicalTrials.gov registration number: NCT03126071).
| S-EPMC11423381 | biostudies-literature
Project description:PurposeNo combined immunotherapy and antiangiogenic therapy have been investigated in exclusively programmed death-ligand 1 (PD-L1)-positive advanced cervical cancer (CA). We investigated the efficacy and safety of sintilimab plus anlotinib as second-line or later therapy for PD-L1-positive recurrent or metastatic (R/M) CA.Patients and methodsPatients with PD-L1-positive (Combined Positive Score ≥ 1) R/M CA who progressed after at least one prior systemic chemotherapeutic regimen or could not tolerate chemotherapy were eligible for the phase II trial. The patients received 200 mg sintilimab once on day 1 and 10 mg anlotinib once daily on days 1-14 every 3 weeks. The primary end point was investigator-confirmed objective response rate (ORR) per RECIST v1.1. Secondary end points included progression-free survival (PFS), overall survival, and disease control rate. Biomarkers were explored.ResultsForty-two patients were enrolled. The ORR was 54.8% (95% CI, 38.7 to 70.2). In 39 efficacy-evaluable patients, the ORR was 59.0% (95% CI, 42.1 to 74.4); the disease control rate was 94.9% (95% CI, 82.7 to 99.4). The median PFS was 9.4 months (95% CI, 8.0 to 14.6). The median overall survival was not reached. Furthermore, 85.8% of the patients experienced treatment-related adverse events. The most frequent treatment-related adverse events were hypothyroidism (33.3%), elevated aspartate aminotransferase levels (21.4%), and hypertension (19.0%). Patients with altered PIK3CA, PI3K-AKT signaling, or KMT2D had a higher ORR, whereas those with altered STK11 and/or JAK2 had a significantly shorter PFS.ConclusionSintilimab plus anlotinib as second-line or later therapy is efficacious and safe for patients with advanced CA who have failed prior chemotherapy.
| S-EPMC9148684 | biostudies-literature
Project description:ObjectiveAnlotinib, a novel multitarget kinase inhibitor of VEGFR, FGFR, PDGFR and c-Kit, has proven to be effective and safe for refractory soft tissue sarcoma patients, but has not been examined in recurrent or metastatic primary malignant bone tumors in a clinical trial setting.MethodsThis is a multicenter single-arm trial. Patients with pathologically proven recurrent or metastatic primary malignant bone tumors were eligible. Anlotinib was administered orally at 12 mg per day. Each cycle consisted of 2 weeks of treatment followed by 1-week off-treatment. The primary endpoint was progression-free survival (PFS), as assessed in the intention-to-treat (ITT) population. Secondary endpoints included objective response rate (ORR), disease control rate (DCR) and overall survival (OS). Adverse events (AEs) were assessed per NCI CTCAE version 4.03.ResultsA total of 42 patients were enrolled. Median PFS was 5.3 months (95% CI 3.5-8.4 months) in the overall analysis, 4.8 months (95%CI 3.5-7.1 months) in osteosarcoma patients and 2.8 months [95%CI 1.3 months to not reached (NR)] in chondrosarcoma patients. The median OS was 11.4 months (95% CI 10.1 months to NR) in the overall analysis, not reached (95% CI, NR, NR) in osteosarcoma patients and 11.4 months (95% CI 1.8 to 21.1 months) in chondrosarcoma patients. The ORR was 9.52% and DCR was 78.57%. Grade 3 or above AEs occurred in 54.76% of the patients, and included hypertension (19.05%), hypertriglyceridemia (9.52%) and pustulosis palmaris et plantaris (7.14%). No treatment-related death was reported.ConclusionAnlotinib demonstrated promising antitumor activities in recurrent or metastatic primary malignant bone tumors with manageable AEs.
| S-EPMC9177947 | biostudies-literature
Project description:BackgroundThe efficacy and safety of chemotherapy strategies combining the multi-target receptor tyrosine kinase inhibitor in patients with advanced EGFR/ALK wild-type non-squamous non-small-cell lung cancer (nsq-NSCLC) are undetermined. We aimed to investigate the efficacy and safety of anlotinib combined with carboplatin/pemetrexed-based chemotherapy followed by maintenance therapy (anlotinib plus pemetrexed) in advanced EGFR/ALK wild-type nsq-NSCLC.MethodsEligible patients with wild-type EGFR/ALK advanced nsq-NSCLC who received first-line therapy in Henan Province from March 2019 to February 2021 were recruited. All patients were treated with anlotinib in combination with carboplatin/pemetrexed-based chemotherapy, followed by maintenance therapy (anlotinib plus pemetrexed). The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival (OS), disease control rate (DCR), objective response rate (ORR), and adverse events (AEs). Response and AEs were assessed based on the Response Evaluation Criteria in Solid Tumors (1.1) and National Cancer Institute - Common Terminology Criteria for Adverse Events v.4.0.3, respectively. The follow-up interval for survival was 6 weeks and the safety follow-up was performed until the end of treatment. Kaplan-Meier analysis was used to calculate the median PFS and OS.ResultsThirty-eight participants with median age of 62 (range, 33-75) years were evaluated. Five participants were still on maintenance therapy until the end of the study. The majority were non-smokers (68.4%). The median follow-up was 13.6 (range, 12.3-14.9) months. The median PFS (mPFS) was 10.5 (95% CI: 4.1, 17.0) months, and the median OS was 23.4 [95% CI: not evaluable (NE), NE] months. The DCR and ORR were 94.7% and 60.5%, respectively. Grade 3 and above treatment-related adverse events (TRAEs) happened to 12 participants. The most common TRAEs were hypertension (23.7%), neutropenia (19.4%), and bone marrow toxicity (10.5%). Seven patients discontinued treatment, including two patients during induction and five patients during maintenance treatment. No grade 5 TRAE was reported. In the non-smoker participants, the mPFS was 14.5 (95% CI: 4.0-25.0) months.ConclusionsAnlotinib in combination with carboplatin/pemetrexed-based chemotherapy followed by anlotinib plus pemetrexed as maintenance therapy might be an effective choice in treating patients with wild-type EGFR/ALK advanced nsq-NSCLC.
| S-EPMC9459624 | biostudies-literature