The combination of standard chemoradiotherapy plus avelumab demonstrated clinical activity while maintaining a tolerable safety profile for patients with locally advanced rectal cancer.
The preoperative use of chemoradiotherapy in combination with avelumab (Bavencio) yielded promising activity and a manageable safety profile for patients with locally advanced rectal cancer, according to results from the phase 2 AVANA study (NCT03854799) presented at the 2021 ESMO World Congress on Gastrointestinal Cancer.
The primary end point of pathological complete response (pCR) was observed in 23% of patients (95% IC, 16%-32%) and major pathologic response was observed in 60% (95% IC, 50%-69%) of patients. Additionally, 17% of patients did not experience a response.
A total of 101 patients with resectable locally advanced rectal cancer were enrolled across 10 Italian centers between April 2019 and November 2020. Patients were treated with standard chemoradiotherapy plus avelumab 10mg/kg every 2 weeks for 6 cycles. Patients then underwent total mesorectal excision (TME) at week 8 to 10 after treatment with standard chemoradiotherapy. Patients would then receive adjuvant chemotherapy according to their pathological response for 6 cycles.
Key secondary end points for the study included R0 resection, tumor downstaging, local recurrence, sphincter preservation rate, progression-free survival, overall survival (OS), safety profile, and evaluation of exploratory predictive and/or prognostic biomarkers.
Sixty-one percent of patients who enrolled on the study were male and investigators reported a median age of 63 years (range, 23-82). A total of 93 patients had an ECOG performance status of 0, with the remaining 8 having a performance status of 1. Furthermore, patients had reported cT stages of cT1 (n = 3), cT2 (n = 8), cT3 (n = 74), and cT4 (n = 16). Additionally, reported cN stages included cN0 (n = 6) and cN-positive (n = 95).
In terms of pre-operative treatment compliance and surgery timing, 99 patients received the full dose of radio therapy, 91 patients were given the full dose of capecitabine, and 92 were treated with the full dose of avelumab. In total, 46 patients waited 9 to 10 weeks after chemoradiotherapy to undergo surgery and 53 waited for over 10 weeks. Two patients waited for an unknown period of time.
Of the 62 patients with evaluable microsatellite status, 8% of those with microsatellite stable disease experienced a pCR, 69% experienced a major pathological response, and 23% did not experience a response. Of the 2 patients who were microsatellite instability–high, 1 had a pCR and the other had a major pathologic response.
Common any grade adverse effects (AEs) included diarrhea (33%), asthenia (19%), anemia (14%), thrombocytopenia (14%), rectal bleeding (14%), nausea (12%), and proctalgia (12%). Grade 3 or higher AEs included diarrhea (3%), nausea (2%), neutropenia (1%), vomiting (1%), and asthenia (1%).
Some of the more common any grade immune-related AEs (irAEs) included skin reaction (7%), infusion reaction (4%), glycemia increase (4%), and hypothyroidism (3%). Grade 3 or higher irAEs included infusion reaction (2%), heart failure (1%), and alanine aminotransferase increase (1%). Serious AEs were observed in 4% of patients and included diarrhea, infusion reaction, uncontrolled pain, and heart failure.
The investigative team is still awaiting longer term follow-up data regarding disease-free survival and OS among the patients who received the experimental regimen. Translational analyses on biological samples to identify which patients would benefit from the chemoradiotherapy plus avelumab combination are ongoing.
Salvatore L, Bensi M, Corallo S, et al. Phase II study of preoperative (PREOP) chemoradiotherapy (CTRT) plus avelumab (AVE) in patients (PTS) with locally advanced rectal cancer (LARC): the AVANA study. Presented at 2021 ESMO World GI; June 30-July 3, 2021; virtual. Accessed August 31, 2021.https://bit.ly/3t5p7V8