Safety and effectiveness analysis of neoadjuvant chemoradiation plus consolidative chemotherapy with concurrent anti-PD-1 therapy in mid-low locally advanced rectal cancer

Nowadays, neoadjuvant chemoradiation (nCRT) has become a standard of care for mid-low locally advanced rectal cancer (LARC). Indeed, nCRT plus different cycles of consolidative chemotherapy can result in various extents of increase in pCR rate comparing to nCRT alone. In this situation, several investigators begin to explore whether inductive anti-PD-1 therapy before nCRT, or adding anti-PD-1 therapy to nCRT and/or consolidative chemotherapy can further increase the pCR rate or not. Recently, data from several phase II trials support this proposal, indicating that the pCR rate will be increased if adding anti-PD-1 therapy to consolidative chemotherapy. On this basis, we intend to investigate whether more cycles or even full cycles of consolidative chemotherapy plus concurrent anti-PD-1 therapy is feasible among LARC patients, who initially cannot be managed by radical surgery.

This single-arm, phase Ib study is designed to recruit LARC patients (n = 30), who are classified into ‘Bad’ or ‘Advanced’ risk group according to ‘ESMO-2017 Rectal cancer Clinical Practice Guidelines’. Their ECOG scores are of 0 – 1, aged from 18 – 80 years-old, who are certified as tubular adenocarcinoma by histological diagnosis. nCRT is administrated 50 – 50.4 Gy in 25 – 28 fractions over 5 – 5.5 weeks with concurrent Capecitabine (825mg/m2). 7 – 10 days after the last fraction of nCRT, the first cycle of CapeOX chemotherapy plus anti-PD-1 therapy (Sintilimab, 200mg, i.v., d1) will be administered. Evaluation of treatment efficacy is carried out after completing the first 3 cycles of CapeOX plus Sintilimab by using digital rectal examination, pelvic high-resolution MRI, total abdominal CT, lung CT, endorectal ultrasound, and endoscopy. If achieving a satisfying shrinkage of primary tumor or exhibiting a poor tolerance to consolidative treatment, radical surgery can be considered. If not, another 3 cycles of CapeOX plus Sintilimab will be administered. Thereafter, radical surgery will be performed. Or else, if achieving cCR, the ‘Watch-and-Wait’ strategy can be considered. Patients were divided into ‘Semi’ arm which received three cycles of CapeOX plus Sintilimab, or ‘Full’ arm received six cycles of that. Prior to each cycle of consolidative treatment, toxicities related to chemotherapy and immune-checkpoint inhibitors were monitored. Adverse events were documented according to Common Terminology Criteria for Adverse Events Version 5.0. The primary end point is the incidence of serious adverse event (that is any grade 3 or higher treatment-related adverse event), and the secondary end point was complete response rate (CR), which defined as cCR or pCR achieved after consolidative treatment or radical surgery. Then, the incidence of serious adverse event and CR rates are compared between the two arms.

Clinical trial information: NCT04906044

The authors.

This trial was supported by [National Natural Science Foundation of China] under Grant [number 82272738].

X. Sun: Disclosures not submitted. P. Chang: Disclosures not submitted. All other authors have declared no conflicts of interest.