4046 Background: Perioperative chemotherapy improves cure rate in locally advanced gastroesophageal adenocarcinoma (GEA), and immune checkpoint inhibitors are active at the metastatic stage. This trial tests the hypothesis that the addition of avelumab to perioperative chemotherapy will increase the major pathologic response (MPR) rate in comparison with historical controls. Methods: Phase II study of avelumab + chemotherapy (docetaxel, cisplatin and 5-FU or mDCF) given every 2 weeks for 4 cycles before and after surgery. Main inclusion criteria: GEA, cT3 and/or cN+, M0, WHO PS 0-1. Main exclusion criteria: use of immunosuppressants, serious autoimmune disease, daily intake >10 mg prednisone. Staging studies: CT, PET-CT, endoscopic ultrasound, diagnostic laparoscopy. Surgical resection: D2 lymphadenectomy, en-bloc esophagectomy for type I/II gastroesophageal junction (GEJ) tumors. Aim of the study: MPR as defined as tumor regression grades 0-1 (modified Ryan scheme); as per hypothesis, this experimental regimen will result in a 20% rate of MPR, compared with 7% with chemotherapy alone. Simon 2-stage design: if less than 2 MPR are seen in the first 16 patients, the study will be closed. The study hypothesis cannot be rejected if at least 6 MPR are seen in the first 50 patients. All adverse effects are prospectively recorded per CTCAE guidelines in patients who have received at least one treatment cycle. Survival rates are calculated with Kaplan-Meier method. Preliminary results are presented since the study has met its primary endpoint. Results: Feb 2018-Feb 2020: 28 patients enrolled (25 M/3 F, age 45-78). Location: GEJ (23), stomach (5). Staging: cT3 (25), cT4 (1), cN+ (20). Biomarkers expression: mismatch repair (MMR) protein loss (3/28); PD-L1(clone 73-10) expression in 1% (TPS) or more of tumor cells seen in 12/28 samples, and >10% in 6 patients. Grade 3 toxicity: stomatitis (2/28); nausea (2/28); vomiting (1/28); diarrhea (1/28); hypothyroidism (1/28); arthralgia (3/28); neutropenia (1/28). Grade 4 toxicity: pneumonia (1/28); neutropenia (2/28). Postoperative 30-day mortality: 0%. One patient was excluded from efficacy analyses for M1 staging; 27 patients underwent surgery, 26 with R0 (96%). Six cases (22%) show MPR: 3 grade 0 (11%) and 3 grade 1 (11%) tumor regressions. No correlation was seen between MMR proteins or PD-L1 expression and tumor regression. With a median follow-up of 1.5 years (range 0.4-2.5), the disease-free survival rate is projected to be 0.92 (95% CI 0.83-1.00) at 12 months and 0.77 (95% CI 0.58-1.00) at 24 months. Conclusions: The combination of mDCF chemotherapy with Avelumab demonstrates a promising safety and activity profile. Ongoing laboratory investigations are underway to correlate our findings with tumor molecular features before exposure to treatment. Clinical trial information: NCT03288350.

We present a case of persistent postpartum hypertension found to be secondary to primary hyperaldosteronism in a woman with a history of recurrent hypertensive disorders of pregnancy and associated fetal complications. Our systematic review revealed only 18 cases of primary aldosteronism diagnosed in women with postpartum hypertension, suggesting that this disorder is under-studied in the postpartum period. A review of these cases suggests that women with primary hyperaldosteronism commonly present with hypertensive disorders of pregnancy, but may only be identified de novo postpartum. However, a high index of suspicion is needed to diagnose primary hyperaldosteronism in the postpartum period, guided by a woman’s obstetric history.

Background: Antiangiogenic therapy in combination with chemotherapy has shown improved clinical benefit in advanced cancer. In third-line therapy, apatinib(a TKI against VEGFR-2) has shown good safety and efficacy for advanced gastric cancer. However, the safety and efficacy of apatinib combined with docetaxel in second-line treatment of advanced gastric cancer remains unclear.Methods: From Mar 2017 to Dec 2018, 40 patients with advanced gastric cancer after failure of first-line chemotherapy were enrolled in this open-lable, prospective study. All patients were treated by apatinib (500mg, qd, adjust the dosage to 250mg according to the patient's tolerance) with docetaxel (60mg/m 2 ,d1, q21d). According to the docetaxel course of treatment, study treatment was continued as a 21-day cycle. After 6 cycles, apatinib alone maintenance. Efficacy was evaluated every 2 cycle based on RECIST version 1.1. The primary endpoint was progression-free survival (PFS). The secondary endpoints were objective response rate (ORR), disease control rate (DCR), overall survival (OS), safety and quality of life.Results: During the experiment, it was found that efficacy of apatinib 500 mg group was better than 250 mg group. Stratified analysis showed that the median PFS in the 500 mg (n ¼ 24) group was 1.5m longer than that in the 250 mg (n ¼ 16) group(4.6m vs 3.1m). In terms of safety, the incidence of adverse events in the 500mg group was similar to that in the 250mg group, mainly hypertension (75.0% vs 62.5%), vomiting (50.0% vs 31.3%) and hematological toxicity (37.5% vs 37.5%); Adverse events were manageable and there were no treatment-related deaths.Conclusions: Data demonstrated that patients given apatinib at the dose level of 500 mg once daily showed better effectiveness to 250 mg. Besides, the toxicities could be tolerable and controllable.

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A lack of FDG-PET response to neoadjuvant chemotherapy for gastroesophageal adenocarcinoma is considered as indicative of a poor prognosis, whereas pathologic complete or near-complete response (pCR/near-pCR) predicts a more favorable outcome. In a single-arm phase II trial of perioperative immunochemotherapy, we sought to establish a correlation between the results of an FDG-PET performed after the neoadjuvant part of the treatment and the pathologic results obtained after surgery. Methods Inclusion criteria: locally advanced gastroesophageal adenocarcinoma (T3 and/or N+); adequate organ function; ECOG PS 0–1; no contraindication to immunotherapy; Staging: CT, FDG-PET, EUS, diagnostic laparoscopy. Eligible patients receive docetaxel/cisplatin/5-FU (mDCF) on day 1 and avelumab on day 4 of each 2-week cycle and are restaged after 4 cycles. FDG-PET response is defined as reduction of >35% of pre-treatment SUV. Surgery is performed if no disease progression. Four cycles of mDCF/avelumab are administered after surgery. Tumor regression is scored from 0 (no tumor cells) to 3 (no tumor regression). The primary endpoint is the pCR/near-PCR rate (score 0–1). Results As of February 24, 2020, 28 patients have been enrolled and 22 have been operated. Paired FDG-PET response and pathologic response data are available for 21 patients. We observed 16/21 FDG-PET responses and 6/21 pCR/near-pCR. Of the latter, 4 were associated with an FDG-PET response and 2 with no FDG-PET response. Ten patients with score 3 tumor regression had had FDG-PET response. No statistical correlation could be found between FDG-PET response and likelihood of pCR/near-pCR. Conclusion Given the discrepancy observed between FDG-PET and pathologic results, the need for a repeat FDG-PET for gastroesophageal adenocarcinoma after neoadjuvant immunochemotherapy and before surgery should be questioned. Analysis of the tumor microenvironment could possibly explain these results. Future studies will look into correlation between the results presented and survival.