507O - 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

Background

FOLFOX or CAPOX-based adjuvant chemotherapy is the standard of care for operable stage III colorectal cancer (CRC), but it causes disabling neurotoxicity. We previously found a higher level of toxicity in patients receiving > 3.09 mg of oxaliplatin (Ox) per kg of lean body mass (LBM). We assessed whether an LBM-based Ox dose reduced Ox-induced peripheral neurotoxicity (OIPN).

Methods

We included CRC patients eligible for adjuvant Ox chemotherapy (NCT032554347). Group 1 (no LBM reduction) received a body surface area (BSA)-based Ox dose (85 mg/m²). Patients with LBM reduction were randomized (1:1) (stratification by center, age, and weight loss) to receive a BSA-based (group 2) or a LBM-based Ox dose (3.09 mg/kg LBM) (group 3). The primary endpoint was the percentage of patients without grade ≥ 2 OIPN during the first 6 cycles of treatment. To compare groups 2 and 3, 108 randomized patients were required (two-sided α = 0.05, 80% power).

Results

We included 160 patients: 33, 64, and 63, in groups 1, 2 and 3, respectively (median age: 63 years, 52.5% males, 89.3% ECOG 0). Tumor stage was pT3 (57.5%), pT4 (33.8%), pN1 (60.6%), and pN2 (38.1%). During the first 6 cycles of treatment, 67.2% of patients in group 3 had no grade ≥2 OIPN compared to 42.1% in group 2 (p=0.01). Group 3 has a better Grade ≥ 2 OIPN-free survival (HR 0.53 [95% CI 0.34-0.84], p=0.01) and a longer time to onset of grade ≥ 2 OIPN (p = 0.006). Patients in group 3 could receive a higher cumulative Ox dose without grade ≥ 2 OIPN (p= 0.044), and had higher Ox dose reductions (p<0.001). The duration of grade ≥ 2 OIPN and the number of OIPN-based interruptions of Ox treatment (p=0.908) were similar. At a median follow-up of 38.6 months, both groups had similar relapse-free survival (RFS) (HR 1.05 [95% CI 0.54-2.06] p=0.88) and overall survival (OS) (HR 1.20 [95% CI 0.36-3.92] p=0.77). The QLQ CIPN20 score, focusing on neurotoxicity, was significantly better in group 3.

Conclusions

In adjuvant setting, administering Ox-based treatment with an LBM-based Ox dose should be systematically performed. It significantly reduces OIPN and improves quality of life without negatively impacting RFS and OS.

Clinical trial identification

NCT03255434.

Editorial acknowledgement

The authors thank Dr. Fanny Salasc of the Montpellier Cancer Institute (ICM), Montpellier, France for providing medical writing and editorial support.

Legal entity responsible for the study

Montpellier Cancer Institute (ICM), Montpellier, France.

Funding

This work was funded by the French Ministry of Health (PHRC-K 15-209) and the National Institute of Cancer (INCA DOM n°2019-207).

Disclosure

E. Assenat: Financial Interests, Speaker, Consultant, Advisor: Roche, Novartis, MSD, AstraZeneca, Bayer, Ipsen, Boston, Incyte, Servier, AAA. H. Perrier: Non-Financial Interests, Advisory Board: Seagen, Servier, Amgen, Merck, Bayer, Roche. F. Khemissa Akouz: Financial Interests, Personal, Invited Speaker: Servier, AstraZeneca; Other, Fees for congress (JFHOD): MSD; Other, Fees for congress: Servier. C. Lepage: Financial Interests, Personal, Advisory Board: AAA; Financial Interests, Personal, Invited Speaker: Amgen, Pierre Fabre, Ipsen. All other authors have declared no conflicts of interest.