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Efficacy and safety of neoadjuvant chemoradiotherapy plus apatinib for patients with locally advanced, HER2-negative, Siewert's type II-III adenocarcinoma of esophagogastric junction: a single-arm, open-label, phase II trial.

ABSTRACT: This study aimed to investigate the efficacy and safety of concurrent neoadjuvant chemoradiotherapy (CRT) plus apatinib in treating locally advanced, HER2-negative, Siewert's type II-III adenocarcinoma of esophagogastric junction (AEG) patients. Thirty eligible patients were analyzed in this single-arm, open-label, phase II trial. Patients received neoadjuvant regimen as follows: two cycles of apatinib (orally, 250 mg/day on day 1-28), two cycles of capecitabine (orally, 1,000 mg/m² twice daily on day 1-14), oxaliplatin (intravenously, 130 mg/m² on day 1), and concurrent radiotherapy (a total dose of 45 Gy in 25 fractions) started on day 1 of chemotherapy. Then, surgery was performed within 8-12 weeks after the completion of neoadjuvant therapy. This trial was registered on the ClinicalTrials.gov website (access number: NCT03349866). After neoadjuvant CRT plus apatinib treatment, 18 (60.0%) patients achieved objective response, 29 (96.7%) patients achieved disease control, and 20 (66.7%) patients achieved down-staging. Encouragingly, tumor regression grade (TRG) 0, TRG 1, TRG 2 and TRG 3 were observed in 33.3%, 20.0%, 30.0% and 10.0% patients, respectively; the pathological complete response rate was 33.3%, and the R0 resection rate was 93.3%. Regarding survivals, the 1-year and 2-year progression-free survival rates were 96.7% and 88.1%, respectively. Meanwhile, the 1-year and 2-year overall survival rates were 100.0% and 96.6%, respectively. As to safety, the majority of the adverse events were of mild grade, and the post-operative complications were manageable. In conclusion, neoadjuvant CRT plus apatinib exhibits high efficacy and acceptable tolerance in patients with locally advanced, HER2-negative, Siewert's type II-III AEG.

SUBMITTER: Guo H

PROVIDER: S-EPMC8430131 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundFew studies have evaluated the significance of sarcopenia in predicting the outcomes of patients with adenocarcinoma of the esophagogastric junction (AEG), especially those who received neoadjuvant chemoradiotherapy (NCRT). We aimed to identify the sarcopenic status and its impact on the outcomes of patients with locally advanced AEG who received NCRT followed by radical surgery or systemic therapy.Materials and methodsPatients with T3-4N+M0 AEG with accessible abdominal computed tomography (CT) before and after NCRT were retrospectively analyzed. Body composition parameters, particularly the skeletal muscle index (SMI), were assessed using a CT-based method, and sarcopenia was defined using a predetermined SMI cutoff value. Survival analysis was conducted using the Kaplan-Meier method. A Cox proportional hazards regression model was used to identify independent prognostic factors. Receiver operating characteristic curve analysis was carried out, and the area under the curve (AUC) was calculated to test the prognostic accuracy of different factors.ResultsA total of 63 patients were enrolled, 65.1 and 79.4% of whom developed pre- and post-NCRT sarcopenia, respectively. Patients with pre-NCRT sarcopenia had lower radical surgery rates (70.7 vs. 95.5%, p = 0.047) than those without sarcopenia; however, sarcopenic status did not affect other short-term outcomes, including treatment-related toxicity and efficacy. Pre-NCRT sarcopenia was identified as an independent predictive factor for poor overall survival (OS) [adjusted hazard ratio (HR), 6.053; p = 0.002] and progression-free survival (PFS) (adjusted HR, 2.873; p = 0.031). Compared with nutritional indices such as the Nutritional Risk Screening 2002, weight loss during NCRT, and post-NCRT sarcopenia, pre-NCRT sarcopenia was regarded as the best predictive index for the 5-year OS (AUC = 0.735) and PFS rates (AUC = 0.770).ConclusionPre-NCRT sarcopenia may be an independent predictive factor for OS and PFS rates in patients with locally advanced AEG receiving multimodal treatment.

Project description:BackgroundAdding anti-angiogenics to neoadjuvant chemotherapy for localized gastric cancer is recognized as a promising strategy, but its clinical value remains to be defined.MethodsThis single-center, single-arm, phase 2 trial included patients with locally advanced (cT3/4aN+M0) adenocarcinoma of the stomach or gastroesophageal junction (GEJ) who received three cycles of intravenous oxaliplatin (135 mg/m2 on day 1), oral capecitabine (1000 mg/m2 twice daily on days 1 to 14), and oral apatinib for 21 days (250 mg once daily in the first two cycles, and further increased to 500 mg daily in the third cycle based on whether any adverse event of grade 3 or worse occurred), and an additional cycle of oxaliplatin plus capecitabine, followed by gastrectomy with D2 lymphadenectomy. The primary endpoint was the proportion of patients who achieved an objective response according to RECIST version 1.1.ResultsBetween April 28, 2017, and October 23, 2019, 37 patients were screened and 35 participants were included. Of the 32 patients assessable for efficacy and safety, objective responses were achieved in 25 (78.1%; 95% confidence interval [CI], 60.0% to 90.7%) patients. Thirty-one (96.9%) patients received R0 resection, two (6.3%) patients achieved pathological complete response, and 11 (34.4%) patients achieved pathological response. At the data cutoff date (September 30, 2021), the median event-free survival was 42.6 (95% CI, 16.2 to not reached) months, and the median overall survival was not reached. The most common grade 3 or 4 treatment-emergent adverse events were hypertension (9/32, 28.1%), thrombocytopenia (7/32, 21.9%), and neutropenia (5/32, 15.6%). Seven (21.9%) patients developed surgical complications, and the most common one was intra-abdominal abscess (4/32, 12.5%).ConclusionsThe concomitant use of apatinib, oxaliplatin, and capecitabine as neoadjuvant therapy showed promising efficacy and manageable safety profile in patients with locally advanced adenocarcinoma of the stomach or GEJ, and further phase 3 study is warranted.Trial registrationThis study was registered with ClinicalTrial.gov ( NCT03229096 ).

Project description:BackgroundThe anti-tumor activity and acceptable tolerability of pyrotinib plus chemotherapy have been demonstrated in phase III trials in human epidermal growth factor receptor 2-positive metastatic breast cancer (BC). In this study, we assessed the efficacy and safety of neoadjuvant pyrotinib plus trastuzumab and albumin-bound paclitaxel in women with human epidermal growth factor receptor 2-positive early or locally advanced BC.MethodsIn this single-arm exploratory phase II trial, patients with untreated human epidermal growth factor receptor 2-positive BC (stage IIA-IIIC) received pyrotinib 400 mg once daily, trastuzumab 4 mg/kg loading dose, followed by 2 mg/kg once a week, and albumin-bound paclitaxel 125 mg/m2 once a week for four 21-day cycles before surgery. The primary endpoint of the study was total pathological complete response (pCR) rate, defined as no microscopic invasive tumor remnants in the breast and axillary lymph nodes. The secondary endpoints were investigator-assessed objective response rate (ORR) and adverse event profiles.ResultsBetween May 17, 2019 and November 26, 2019, a total of 21 patients were enrolled. The total pCR rate was 57.1% (12/21), whereas 23.8% (5/21) and 19.0% (4/21) of patients had minimal and moderate residual disease (RD), respectively. The ORR reached 100% (21/21) at the end of the neoadjuvant therapy. Grade ≥3 treatment-related adverse events were observed in 42.9% (9/21) of patients, including decreased neutrophil count [7 (33.3%)], diarrhoea [6 (28.6%)], decreased white blood cell count [5 (23.8%)], and vomiting [2 (9.5%)]. Adverse event-related dose reduction and interruption of pyrotinib occurred in 6 (28.6%) and 11 (52.4%) patients, respectively.ConclusionsIn women with human epidermal growth factor receptor 2-positive early or locally advanced BC, neoadjuvant pyrotinib plus trastuzumab and albumin-bound paclitaxel effectively promoted total pCR rate with an acceptable safety profile (ClinicalTrials.gov, NCT04152057).

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Efficacy and safety of neoadjuvant chemoradiotherapy plus apatinib for patients with locally advanced, HER2-negative, Siewert's type II-III adenocarcinoma of esophagogastric junction: a single-arm, open-label, phase II trial.

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