600P - Effectiveness and safety of rectal arterial infusion chemotherapy combined with anti-PD1 antibody for microsatellite stable locally advanced rectal cancer: Early outcome report of a two-stage, single armed, phase II study (RAIC)

Background

The standard neoadjuvant therapy for locally advanced rectal cancer (LARC) is chemoradiotherapy (CRT) which increases perioperative complications. Chemotherapy alone has approximately 60% objective response rate and lower pathological complete response pCR rate compare with CRT. We propose a new strategy (induction chemotherapy followed by arterial infusion chemotherapy and anti-PD1 antibody) to achieve high pCR rate for microsatellite stable (MSS) LARC without radiotherapy.

Methods

Two cycles of Capox were given to eligible LARC patients (tumor located 5-12cm from anal verge). Patients who achieved more than 20% regression of maximum tumor diameter receive 2 cycles of rectal arterial infusion oxaliplatin (50mg, D1) + intravenous anti-PD1 inhibitor (Sintilimab, 200mg, D2) + capecitabine (1000mg/m2, po, twice daily, D1-D14) with 6 weeks before operation. Patients with tumor regression less than 20% were suggested to receive CRT. The primary endpoint is pCR rate. A total of 38 patients (10 in the first stage, 28 in the second) stage are planned to be recruited by Simon’s two-stage design. The second stage will be conducted if more than 2 patients achieve pCR in the first stage, otherwise the trial will be terminated.

Results

A total of 20 patients had been enrolled and 13/20 reached 20% regression criterion after induction chemotherapy and received arterial infusion chemotherapy combined with intravenous anti-PD1 antibody. One patient achieved clinical complete response and refused surgery. Other 12 patients received operation and 4/12 (33.3%) achieved pCR (3/10 in the first stage). According to the tumor regression grading TRGstandard of the eighth edition of AJCC, the patients number of TRG0/1/2/3 was 4/4/2/2, respectively. Among the 12 patients 5 had grade 3 adverse event (abdominal pain and readmission), including one grade 3 immune-related adverse event (dermatitis).

Conclusions

Rectal arterial infusion chemotherapy combined with intravenous anti-PD1 antibody for MSS LARC achieved high pCR rate. The RAIC trial is now progressed to the second stage.

Clinical trial identification

NCT05307198.

Editorial acknowledgement

Legal entity responsible for the study

The Second Affiliated Hospital Zhejiang University School of Medicine.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.