LBA3513 Background: The combination of capecitabine plus long course radiotherapy (RT) is the standard preoperative therapy in cT3-4 cN+ rectal cancer. pathologic complete remission (pCR) can be considered as surrogate endpoint of efficacy of treatment in terms of disease-free survival (DFS). Preclinical data points heavily toward a strong synergy between RT and immune treatments. Methods: This is a prospective phase II, open label, single arm, multicentre study in patient with locally advanced rectal cancer who receive standard concomitant CT/RT therapy (825 mg/m2 twice daily capecitabine every day and 5040 cGy radiotherapy for 5 days per week for 5 weeks) followed by durvalumab (1500 mg Q4W for 3 administrations). Surgery is performed after 10-12 weeks from neoadjuvant therapy. The primary endpoint is the proportion of pCRs after at least 1 cycle of durvalumab; secondary endpoints are the proportion of clinical complete remissions (cCRs) after at least 1 cycle of durvalumab, the proportion of adverse and serious adverse events (NCI CTCAE v5.0). The sample size has been estimated by using the optimal Simon’s two-stage design assuming a null pCR proportion of 0.15 and an alternative pCR percentage of 0.30 (alpha = 0.05, power = 0.80). If more than 4 pCRs were observed in the first 19 enrolled patients, 36 additional patients were to be accrued for a total of 55 evaluable patients. The null hypothesis is rejected if ≥ 13 pCRs are observed in 55 patients. Results: Between November 2019 and August 2021, 60 patients were accrued, of which 55 were evaluable for study objectives. Fifty-two of 55 treated patients received all 3 infusions of durvalumab. After treatment, a clinical response percentage of 81.8% was observed; 3 patients had progression of disease due to local and/or metastases before surgical intervention. Eighteen patients achieved complete pathological response (32.7%), confirmed by central revision. Near complete regression, moderate and minimal regression were observed in 14 (25.5%), 9 (16.4%) and 11 (20.0%) patients respectively. Regarding toxicity, 23 patients (41.8%) had adverse events (AEs) related to durvalumab treatment. Two patients (1.8%) discontinued durvalumab for toxicity. Grade 3 AEs occurred in 4 (7.3%) patients (diarrhea, skin toxicity, transaminase increase, lipase increase and pancolitis). No Grade 4 toxicity was observed. In 20 patients (36.4%) G1-2 AEs related to durvalumab were observed. The most common were endocrine toxicity (hyper/hypo-thyroidism), dermatologic toxicity (skin rash) and gastrointestinal toxicity (transaminase increase, nausea, diarrhea, constipation). Conclusions: This study met its primary endpoint showing a promising activity of neoadjuvant chemo-radiotherapy plus durvalumab in terms of pCR rate and a safe toxicity profile. Clinical trial information: NCT04083365.
Introduction Rectal cancer (RC) commonly affects older patients, a heterogeneous population whose general status may vary from fit to frail. Total Neoadjuvant Therapy (TNT) has been introduced to improve local and systemic control of RC. The aim was to present real-world data of older patients receiving TNT followed by minimally invasive surgery after a multidimensional frailty assessment and verify whether this approach would be feasible and safe. Methods This was a single-center retrospective study which enrolled all patients ≥ 70 years of age with RC who underwent TNT followed by surgery between November 2017 and April 2022. Data regarding cancer characteristics, the duration of neoadjuvant chemoradiotherapy, toxicity and the need for dose reduction were recorded. All patients underwent minimally invasive surgery 12 to 16 weeks after the end of therapy. Intra- and postoperative outcomes were recorded. Pre- and postoperative functional evaluation was carried out in all patients. Results Fifteen patients were enrolled. Mean age was 74 (70-81) years. The median BMI was 26.2 (22-32) kg/m2. The mean distance of the tumor from the anal verge was 5.2 cm. At diagnosis, 14 patients had positive nodes (93.3%), 11 (73.3%) showed involvement of the circumferential margin (CRM+) and 10 (66.6%) had extramural vascular invasion (EMVI+). Ten patients (66.6%) received mFOLFOX-6 and 5 CAPOX (33.3%) followed by chemoradiation (CRT). After CRT, positive nodes were reported in 4 cases (26.6%), CRM+ in 4 (26.6%), and EMVI+ in 1 (6.6%). A laparoscopic transanal total mesorectal excision (taTME) was performed in all cases. Median operative time was 280 minutes (110-420). Median length of stay was 4 days (3-29). One Clavien-Dindo grade 4 complication, no readmissions, and no variations in pre- and postoperative functional status within 30 days from surgery were reported. No patient died within 90 days. No positive distal or CRMs were detected at final pathology. Three pathologic complete responses were reported (20%). Conclusions Total neoadjuvant therapy followed by TME is feasible and safe, even for older patients, with good short-term clinical and oncologic outcomes. Patient evaluation is crucial for maximizing cancer care as fit older patients can tolerate extended treatment to overcome the threat of advanced rectal cancer.
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