A novel regimen of liposomal irinotecan plus capecitabine as total neoadjuvant therapy for locally advanced rectal cancer (LipCap): A phase II trial.

Abstract

e15640 Background: Clinical data on the participation of liposomal irinotecan in neoadjuvant therapy for locally advanced rectal cancer (LARC) is still limited worldwide. This prospective phase II trial aims to evaluate the efficacy and safety of liposomal irinotecan in this treatment field, with the goal of establishing a novel therapeutic option for LARC. Methods: Patients diagnosed with LARC (cT3-4NanyM0) were enrolled. Treatment commenced with long-course concurrent chemoradiotherapy (LCRT, 50.4Gy/28f). The concurrent chemotherapy regimen consisted of capecitabine (625 mg/m²bid on days of radiotherapy) and liposomal irinotecan (50 mg/m²on the first and 14th days of radiotherapy). After completing LCRT, consolidation chemotherapy comprising 4-6 cycles of liposomal irinotecan plus capecitabine was administered. The primary endpoint was the rate of pathological complete response (pCR). Secondary endpoints encompassed the rates of major pathological response (MPR) and clinical complete response (cCR), the incidence of adverse events (AEs), as well as 3-year progression-free survival and overall survival. The trial was registered with ClinicalTrials.gov (identifier: NCT06210971). Results: Between February 2024 and March 2025, 60 patients were enrolled and initiated neoadjuvant chemoradiotherapy. Of these, 57 proceeded to consolidation chemotherapy upon completion of the initial phase. Ultimately, 47 patients underwent surgical resection, all of whom achieved R0 resection. Pathological evaluation confirmed a pCR in 10 (21.3%) surgical patients and a MPR (defined as TRG 0–1) in 23 (48.9%). Among the 10 patients who did not undergo surgery, 3 achieved a cCR, resulting in an overall complete response rate (pCR + cCR) of 21.7% (13/60) for the entire cohort. The incidence of grade 3–4 AEs was 16.7%, with the most common being diarrhea (10.0%) and leukopenia (5.0%). Other notable AEs included anemia (3.3%), thrombocytopenia (1.7%), and neutropenia (0%). Conclusions: Combining a promising pathological response with a more manageable toxicity profile, this regimen offers a well-tolerated and effective alternative for TNT in LARC. Clinical trial information: NCT06210971 . Baseline characteristics of eligible patients. Characteristic Total (n = 60) Sex Male 44 (73.3%) Female 16 (26.7%) Age Median (Range) 60 (31-74) Clinical T stage cT3 46 (76.7%) cT4 14 (23.3%) Clinical N stage N0 3 (5%) N1 13 (21.7%) N2 44 (73.3%) Clinical stage II 3 (5%) III 57 (95%) Distance from primary tumor to anal verge ≤5cm 27 (45.0%) 5-10cm 33 (55.0%) EMVI Positive 19 (31.7%) Negative 41 (68.3%) MRF Positive 25 (41.7%) Negative 35 (58.3%) EMVI, extramural vascular invasion; MRF, mesorectal fascia.