More highlights in Colorectal Cancer

Other recent trials showing promise in colorectal cancer include the POCHI trial, assessing pembrolizumab-based combination therapy in mismatch-repair proficient/microsatellite stable metastatic colorectal cancer (pMMR/MSS mCRC), and the LEANOX trial, demonstrating that lean body mass (LBM)-based dosing strategies can reduce oxaliplatin-induced neurotoxicity.

Promising efficacy of pembrolizumab plus CAPOX plus bevacizumab in pMMR/MSS mCRC

Currently, immune checkpoint inhibitors are considered ineffective for patients with pMMR/MSS mCRC. However, immunogenic cell death induced by chemotherapy can increase the efficacy of immune checkpoint inhibitors. High levels of tumour infiltrating lymphocytes (TILs) have also been associated with a good prognosis [1].

The ongoing, single-arm, phase 2 POCHI trial (NCT04262687) evaluated the efficacy of pembrolizumab in combination with CAPOX and bevacizumab as first-line treatment of unresectable pMMR/MSS mCRC patients with a high immune infiltrate, defined by at least 1 positive immune score (Immunoscore® and/or TuLIS) on primary tumour resection. The primary objective was the number of participants alive and without progression at 10 months. The trial is still enrolling but Prof. David Tougeron (Poitiers University Hospital, France) presented the first results obtained from 30 participants [2].

After a median follow-up of 21 months, 5 participants (17%) had a complete response, 17 (57%) had a partial response, and 8 (27%) had stable disease (overall response rate 74%; disease control rate 100%). The median duration of response was 10 months. At 24 months of follow-up, progression-free survival was 24.7% and overall survival was 79.9%. At least 1 treatment-related adverse event of grade 3–4 was observed in 70% of the participants.

LBM-based oxaliplatin dose significantly reduces oxaliplatin-induced peripheral neurotoxicity

FOLFOX or CAPOX adjuvant chemotherapy is the current standard-of-care for operable stage III colorectal cancer (CRC), but it is often associated with disabling neurotoxicity. Previously, a low LBM was shown to be a significant predictor of toxicity and neuropathy in patients administered FOLFOX regimens using conventional body surface area (BSA)-based dosing [4].

The multicentre, phase 2 LEANOX trial (NCT03255434) assessed oxaliplatin-induced toxicity in BSA-based oxaliplatin dosing (n=64) and LBM-based oxaliplatin dosing (n=63) of patients with CRC. The primary endpoint was the percentage of patients without grade ≥2 oxaliplatin-induced peripheral neurotoxicity (OPIN) during the first 6 cycles of treatment. Prof. Eric Assenat (Institut du Cancer de Montpellier, France) presented the results [5].

During the first 6 cycles of treatment, significantly more participants on LBM-based oxaliplatin dosing were without grade ≥2 OPIN than those on BSA-based oxaliplatin dosing: 67.2% versus 42.1% (P=0.011). In addition, in participants on LBM-based oxaliplatin dosing, cumulative oxaliplatin dose without grade ≥2 OIPN was higher (P=0.044), time to onset of the first grade ≥2 OIPN was longer (P=0.01), and there were fewer oxaliplatin dose reductions (P=0.001). No differences were observed in progression-free survival and overall survival between BSA-based and LBM-based oxaliplatin dosing. Finally, quality-of-life (QLQ CIPN20 score) was significantly better for participants on LBM-based oxaliplatin dosing (P=0.03).

1. Emile JF, et al. Eur J Cancer. 2017;82:16-24.
2. Emile JF, et al. Pembrolizumab in combination with CAPOX and bevacizumab in patients with microsatellite stable (pMMR/MSS) metastatic colorectal cancer and a high immune infiltrate: a proof of concept study. Preliminary results of FFCD 1703 POCHI trial. Abstract 502O, ESMO Congress 2024, 13–17 September, Barcelona, Spain.
3. Ali R, et al. Cancer Med. 2016;5:607-616.
4. Assenat E, et al. Impact of lean body mass-based oxaliplatin dosage on neurotoxicity in adjuvant treatment of stage III colorectal cancer: Final results of the phase II randomized multicenter LEANOX trial. Abstract 507O, ESMO Congress 2024, 13–17 September, Barcelona, Spain.

 

Copyright ©2024 Medicom Medical Publishers



Posted on 4 November 20244 November 2024