Oxaliplatin/capecitabine or carboplatin/paclitaxel-based preoperative chemoradiation for resectable oesophageal adenocarcinoma (NeoSCOPE): Long-term results of a randomised controlled trial

Abstract

This is the first randomised study to evaluate toxicity and survival outcomes of two neoadjuvant chemoradiotherapy (CRT) regimens for patients with localised oesophageal adenocarcinoma (OAC) or gastro-oesophageal junction (GOJ) adenocarcinoma. The initial results showed comparable toxicity between regimens and pathological complete response (pCR) rate favouring CarPacRT. Herein, we report survival, progression patterns, and long-term toxicity after a median follow-up of 40.7 months. Methods: NeoSCOPE was an open-label, UK multicentre, randomised, phase II trial. Eightyfive patients with resectable OAC or GOJ adenocarcinoma, cT3 and/or cN1 (TNM v7), suitable for neoadjuvant CRT, were recruited between October 2013 and February 2015.Patients were randomised to OxCapRT (oxaliplatin 85 mg/m 2 on Days 1, 15, and 29; capecitabine 625 mg/m 2 orally twice daily on days of radiotherapy [RT]) or CarPacRT (carboplatin AUC2; paclitaxel 50 mg/m 2 on Days 1, 8, 15, 22, and 29). RT dose was 45 Gy/25 fractions/5 weeks. Both arms received induction chemotherapy (two cycles oxaliplatin 130 mg/m 2 on Day 1, capecitabine 625 mg/m 2 orally twice daily on Days 1e21) before CRT. Surgery was performed 6e8 weeks after CRT.The primary end-point was pCR. Secondary end-points were toxicity, progression-free survival (PFS), overall survival (OS), and patterns of progression. Results: Eighty-five patients were recruited from 17 UK centres. The median OS was 41.7 months (95% confidence interval [CI] 19.6 to not reached) in the OxCapRT arm and was not reached in the CarPacRT arm (multivariable hazard ratio [HR] Z 0.48, 95% CIs: 0.24 e0.95, P Z 0.035). The median PFS was 32.6 months (95% CIs: 17.1 to not reached) in the OxCapRT arm and was not reached in the CarPacRT arm (multivariable HR Z 0.54, 95% CIs: 0.29e1.01, P Z 0.053). In both arms, the distant progression was twice as common as locoregional progression. Conclusions: OS and PFS favoured neoadjuvant CarPacRT over OxCapRT. Distant was more common than locoregional progression; therefore, priority should be given to optimising the systemic treatment component.

(Neo)Adjuvant Treatment of Locally Advanced Esophageal and Gastroesophageal Adenocarcinoma: Special Focus on Sex Differences

“…Patients in both arms additionally received two cycles of induction chemotherapy. In this phase II trial, improved overall survival in the carboplatin and paclitaxel arm was observed (HR 0.48, 95% CI 0.24–0.95, p = 0.035) [ 10 ], underlining the validity of the CROSS regimen. In contrast to the CROSS trial, women demonstrated significantly worse overall survival ( Table 1 ) [ 10 ].…”

Efficacy of early PET-CT directed switch to carboplatin and paclitaxel based definitive chemoradiotherapy in patients with oesophageal cancer who have a poor early response to induction cisplatin and capecitabine in the UK: a multi-centre randomised controlled phase II trial

“…Whilst this is somewhat supported by the improved outcomes seen with a similar FOLFOX regimen for patients receiving dCRT for OAC in the CALGB80803 trial, long-term data from the NeoSCOPE trial suggest superior overall survival with car/pac compared with oxaliplatin and capecitabine in patients receiving neoadjuvant CRT for OAC. 19 , 36 However, it should be noted that in ART-DECO (OSCC 61%, 39% OAC), a dCRT trial which used car/pac as systemic, survival was lower than SCOPE1 which used cis/cap regimen therapy (3 year OS ∼40% vs ∼50%). 22 These data do suggest that the use of cis/cap may be superior, at least when compared with a switch to car/pac, particularly in OSCC.…”

Neoadjuvant Treatment Strategies for Resectable Proximal Gastric, Gastroesophageal Junction and Distal Esophageal Cancer

“…Seven RCTs evaluated neoadjuvant chemoradiation compared to induction chemotherapy and chemoradiation [ 34 , 43 , 44 , 45 , 46 , 47 , 48 ]. One RCT evaluated intratumoral paclitaxel in addition to chemoradiation in a mixed cohort [ 33 ].…”

“…Although clinically significant, the study was underpowered for statistical significance [ 47 ]. Interestingly, NeoSCOPE ( n = 85) evaluated two neoadjuvant chemoradiation regimens (Oxaliplatin + Capecitabine + 45 Gy vs. Carboplatin + Paclitaxel + 45 Gy) with improved OS in the latter treatment group (HR 0.48, 95% CI 0.24–0.95, p = 0.035) [ 48 ]. Lastly, Dewitt et al evaluated a mixed cohort for treatment with intratumoral paclitaxel in conjunction with chemoradiation (cisplatin + 5-FU + 50.4 Gy) compared to chemoradiation with no improvement in OS [ 33 ].…”