Proffered paper session 2: GI, lower digestive

In this video, Dr Francesco Sclafani, digestive oncologist at the Institut Jules Bordet in Brussels, 

summarises the key results of four clinical trials that were presented during the second proffered paper session on lower digestive tumours at ESMO 2024. Three of these studies discussed novel first line treatment strategies for patients with metastatic colorectal cancer (mCRC), while the fourth study addressed CRC patients with refractory disease.

SOLARIS was a double-blind, phase III randomized-controlled trial in which patients with mCRC who received first line therapy with mFOLFOX6 or FOLFIRI in combination with bevacizumab were randomly assigned to receive high-dose vitamin D3 (8,000 IU/day x 14 days followed by 4,000 IU/day) or vitamin D3 at a standard-dose of 400 IU/day.1 The study did not meet its primary endpoint, with a median progression-free survival (PFS) of 11.8 months for high-dose vitamin D3 as compared to 10.3 months with the standard dose (HR[95%CI]: 0.92[0.73-1.16]). Also in terms of response rate the study did not reveal a difference with an objective response rate (ORR) of 51% with the high-dose as compared to 44% with the standard dose (p= 0.12).1

In the single arm, phase II POCHY trial, the combination of CAPOX, bevacizumab and pembrolizumab was evaluated as first-line treatment for patients with mismatch-repair proficient, microsatellite stable (pMMR/MSS) unresectable CRC and a high level of immune infiltration, The latter was defined as testing positive on Immunoscore® and/or the TuLIS test. Of the 196 patients who were screened in the study, 36 (18%) tested positive on at least one score. In these patients, the combination regimen induced a very promising ORR of 74% and a 12-month PFS rate of 51.5%.2

The third first line study that was presented in this session consists of CodeBreak 101. This phase Ib study treated 40 patients with KRAS G12C–mutated mCRC with a combination of sotorasib, panitumumab and FOLFIRI. The treatment was relatively well-tolerated with a 58% incidence of grade ≥3 treatment-related adverse events. Results on efficacy were promising, with an ORR of 78% and a disease control rate (DCR) of 95%. As such, these findings provide further support for the ongoing phase III CodeBreak301 study evaluating the combination of chemotherapy, panitumumab and sotorasib as first line treatment for patients with KRAS G12C-mutated mCRC.3

The fourth and final abstract that was discussed by Dr Sclafani featured the results of the phase III RAMTAS/IKF643 trial. In this study, 428 mCRC patients who were previously treated with oxaliplatin, irinotecan, fluoropyrimidin, anti-EGFR antibodies (when indicated) and anti-angiogenics were randomly assigned to receive trifluridine/tipiracil (FTD/TPI) alone, or FTD/TPI in combination with ramucirumab.4 Despite a significantly longer PFS with the combination therapy (HR[95%CI]: 0.774[0.636-0.949]), the study failed to meet its primary endpoint of OS with a median OS of 7.5 months in the combination arm as compared to 7.1 months with FTD/TPI alone (HR[95%CI]: 0.871[0.708-1.073]). Of note, a subgroup analysis of the study did show a potential benefit of ramucirumab to FTD/TPI in the subgroup of heavily pretreated female patients and in patients with a left-sided primary.4