Abstract 67MO
Background
Almost 90% of rectal cancers are microsatellite stable (MSS) or mismatch repair proficient (pMMR) subtypes for which PD-1 blockade is ineffective. The effectiveness is still limited although the radiation can enhance the responses of MSS/pMMR rectal cancer to PD-1 blockade. Our study aims to investigate whether node-sparing modified short-course irradiation combined with chemotherapy and PD-1 blockade could be more effective in patients with MSS/pMMR Locally advanced rectal cancer (LARC).
Methods
We conducted a open-label, prospective, multicentre, phase II trial using Simon's two-stage design. Eligible MSS/pMMR LARC patients(cT3-4N0/+M0/cT2N+M0) were received node-sparing modified short-course radiotherapy (the irradiated planned target volume included only the primary tumour bed but not the tumour-draining lymph nodes, 25 Gy/5f, 5 Gy/f) followed by 4 cycles of CAPOX and tislelizumab. Total mesorectal excision (TME) will be performed at weeks 14-15. The primary endpoint is the rate of pathological complete response (pCR), with a hypothesis of an increased pCR of 30% compared with historical data of 10% after conventional CRT.
Results
Between Aug 18, 2023 to Apr 20, 2024, a total of 46 patients were screened for eligibility. 33 patients ultimately proceeded to surgery, all achieved R0 resection. pCR (TRG 0) and MPR (TRG0+1) were achieved in 78.8% (26/33) and 90.9% (30/33) patients, respectively.3 (9.1%) patients reached TRG 2, no patients had TRG 3. Treatment-related adverse events (TRAEs) of any grade occurred in 29/34 (85.3%) patients. The most common TRAEs of grade 1 or 2 included proctitis (17/34, 50%), leukopenia (14/34, 41.2%), thrombocytopenia (11/34, 32.4%) and anemia (8/34, 23.5%). Grade 3 TRAEs occurred in 5.9% (2/34) of patients, and Grade 4 TRAEs occurred in 8.8% (3/34) of patients. No grade 5 adverse events and treatment-related deaths were recorded.
Conclusions
The node-sparing radiation combined with chemo-immunotherapy regimens dramatically increased pCR rates in MSS/pMMR LARC with tolerable toxicity, which is a promising modality for the treatment of MSS/pMMR LARC patients.
Clinical trial identification
NCT05972655. Release date: August 2, 2023.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
LBA2 - SKYSCRAPER-06: Efficacy and safety of tiragolumab plus atezolizumab plus chemotherapy (tira + atezo + chemo) vs pembrolizumab plus chemotherapy (pembro + chemo) in patients (pts) with advanced non-squamous non-small cell lung cancer (NSq NSCLC)
Presenter: Mark Socinski
Session: Mini Oral session 2
Resources:
Abstract
LBA3 - Perioperative Pembrolizumab (pembro) Plus Neoadjuvant Chemotherapy (chemo) in Early-Stage Non-Small-Cell Lung Cancer (NSCLC): A 4-Year Update of KEYNOTE-671
Presenter: Margarita Majem Tarruella
Session: Mini Oral session 2
Resources:
Abstract
118MO - Trastuzumab deruxtecan (T-DXd) and pembrolizumab in immuno-oncology (IO)-naive HER2-expressing or HER2-mutant non-small cell lung cancer (NSCLC): Interim analysis of a phase Ib study
Presenter: Antoine Italiano
Session: Mini Oral session 2
Resources:
Abstract
66MO - Durvalumab after radiotherapy (RT) in patients (pts) with unresectable Stage III NSCLC ineligible for chemotherapy (CT): final analysis of the phase 2 DUART study
Presenter: Andrea Riccardo Filippi
Session: Mini Oral session 2
Resources:
Abstract
119MO - Phase I/II trial evaluating the innovative therapeutic cancer vaccine PDC*lung01 in combination with anti-PD-1 in patients (pts) with untreated stage IV non-small cell lung cancer
Presenter: Johan Vansteenkiste
Session: Mini Oral session 2
Resources:
Abstract
120MO - Inupadenant combined with chemotherapy in patients with non-squamous NSCLC progressing on or after immune checkpoint inhibitor therapy: Results from dose-finding part of the A2A-005 trial
Presenter: Kristof Cuppens
Session: Mini Oral session 2
Resources:
Abstract
175MO - Investigating the clinical and immunobiological impact of Orphan Genomic Alterations (OGAs) in advanced NSCLC patients treated with immunotherapy.
Presenter: Alessandra Dodi
Session: Mini Oral session 2
Resources:
Abstract
121MO - Anti-IL-8 (BMS-986253) in combination with nivolumab (NIVO) plus ipilimumab (IPI) in patients (pts) with advanced melanoma: final analysis from the randomized part 2 of the phase 1/2 CA027-002 study
Presenter: Matteo Simonelli
Session: Mini Oral session 2
Resources:
Abstract
176MO - ORCA-010 Oncolytic Therapy: Inducing Tumor-Specific Immune Responses and Activation of Tumor Microenvironment in Treatment-Naïve Prostate Cancer
Presenter: Tanja de Gruijl
Session: Mini Oral session 2
Resources:
Abstract