Abstract 247P
Background
Organ preservation (OP) for pts with rectal cancer (RC) is gaining momentum considering the morbidity associated with total mesorectal excision (TME). Current treatments to achieve OP involve radio- and/or chemotherapy, and while escalation to total neoadjuvant therapy increases OP rates, this is associated with increased toxicity. In the current study, we investigated efficacy of RT, atezo and bev in pts with early and intermediate stage RC with the aim of increasing chances of OP.
Methods
Pts with stage ≤T3ab, N0-1, MRF- RC were treated with 5x5 Gy RT followed by 3 cycles of atezo/bev. The primary endpoint would be met if a (near) clinical complete response(cCR) rate of >25% was achieved at 12 weeks, as measured by endoscopy and MRI. Secondary endpoints include pathologic response, OP rate, safety and relapse free survival. Here we report results from the fully accrued study.
Results
38 pts with MMR proficient (pMMR) and 6 pts with MMR deficient (dMMR) tumors were treated (Table). Results are shown separately. At 12 weeks a (near)cCR was observed in 17/38 (45%, 7 cCR + 10 near cCR) pMMR pts, meeting the primary endpoint. The (near)cCR rates in tumors <40mm or N0 disease were 57% and 59%, respectively. At a median follow-up of 23 months, 16 (42%) pts remain TME-free. Five pts developed distant recurrences, including 1 pt in the OP group. Of 26 pts undergoing tumor excision (21 TME, 5 local excision), 6 had a major pathologic response (MPR), including 2 pCRs. In total, 22/38 pts had either MPR or (near)cCR. All 6 pts with a dMMR tumor had a cCR and remain TME- and disease-free. Grade 3-4 immune-related adverse events were observed in 7% of pts. Table: 247P
| Characteristic | pMMR cohort n = 38 | dMMR cohort n = 6 |
| Median age yrs (range) | 63 (42-79) | 60 (40-83) |
| Male | 30 (79%) | 4 (67%) |
| ECOG PS 0 | 37 (97%) | 5 (83%) |
| 1 | 1 (3%) | 1 (17%) |
| cT-stage ∗ T1-2 | 15 (39%) | 1 (17%) |
| T3ab | 22 (58%) | 5 (83%) |
| T4a | 1 (3%) | 0 |
| cN-stage ∗ N0 | 22 (58%) | 1 (17%) |
| N+ | 16 (42%) | 5 (83%) |
| Tumor size ∗ <40 mm | 23 (61%) | 3 (50%) 3 (50%) |
| ≥40 mm | 15 (39%) | |
| Tumor location ∗ | ||
| Proximal (>10cm from anorectal junction) | 1 (3%) | 0 |
| Mid (5-10 cm from anorectal junction) | 7 (18%) | 2 (33%) |
| Distal (<5cm anorectal junction) | 30 (79%) | 4 (67%) |
∗As assessed on MRI
Conclusions
Short course RT followed by a short treatment of atezo/bev resulted in high rates of clinical and pathologic response and an OP rate of 42% in pMMR and 100% in dMMR tumors. These data suggest that benefit of immunotherapy may be extended to pMMR RC and future studies should explore optimal dosing, sequence and duration of therapy.
Clinical trial identification
NCT04017455.
Legal entity responsible for the study
NKI-AVL - Netherlands Cancer Institute, Amsterdam, the Netherlands.
Funding
Roche/Genentech & the imCORE network.
Disclosure
P.G.M. de Gooyer: Other, Personal, Other, Partner works at MSD: MSD. M. Chalabi: Financial Interests, Institutional, Research Grant: BMS, BMS, Roche Genentech, Roche Genentech, MSD, Agenus; Non-Financial Interests, Advisory Role, Advisory Board: BMS, BMS, MSD; Non-Financial Interests, Advisory Role: Kineta. All other authors have declared no conflicts of interest.