Abstract 92P
Background
Approximately half of colorectal cancer (CRC) cases harbor RAS mutations (mts), which render anti-EGFR antibody therapy ineffective and associated with poorer prognosis compared to RAS wild-type CRC. The most common mts are KRAS exon 2 mts, and novel therapeutic development is underway, particularly targeting KRAS G12C and KRAS G12D mts. However, minor RAS mts (including KRAS non-exon 2 and NRAS mts) represent a rare population with limited clinical data on prognosis. We retrospectively analyzed recurrent or metastatic CRC (mCRC) with focusing on the types of RAS mts.
Methods
Patients who started chemotherapy for mCRC with RAS mts at our institution from August 2018 to December 2023 were enrolled, after the approval of the MEBGEN RASKET-B kit in Japan. Among patients without survival events by the data cutoff, those with a follow-up of less than 24 months were excluded. For patients who relapsed during adjuvant chemotherapy or within 6 months after completion of adjuvant chemotherapy, the start date of treatment was defined as the initiation date of the adjuvant chemotherapy.
Results
A total of 122 patients (pts); 19 pts with minor RAS mts, and 103 pts with KRAS exon 2 mts were included. 2 pts in the KRAS exon 2 mts group had BRAF V600E mts. The median age was 65 years (range 26- 81) in the KRAS exon 2 mts group and 59 years (range 44- 84) in the minor RAS mts group. There were no significant differences in the sex, ECOG PS, and the number of sites of metastasis. There was a significant trend of left-sided predominance in the minor RAS mts group (p=0.012). The median overall survival was 26.7 months (95% confidence interval [CI], 18.6 to 37.6) for the KRAS exon 2 mts group and 23.6 months (95% CI, 13.8 to Not reached [NR]) for the minor RAS mts group (HR 0.92; 95% CI, 0.48 to 1.75; p=0.8).
Conclusions
This study suggested that the prognostic impact of minor RAS mts may be similar to that of KRAS exon 2 mts. In our research, we observed that minor RAS mts CRC predominantly occurred in left-sided tumors. Further investigation into the biology of each RAS mt may be needed to improve the prognosis of CRC.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
N. Sugimoto: Financial Interests, Institutional, Invited Speaker: Eli Lilly, MSD, Pfizer, Dai-ichi Sankyo, Seagen, Ono. T. Kudo: Financial Interests, Personal, Invited Speaker: Merck Biopharma Co., Ltd., Taiho Pharmaceutical Co., Ltd., Bristol Myers Squibb K.K., MSD Co., Ltd., Ono Pharmaceutical Co., Ltd.; Financial Interests, Personal, Advisory Board: Daiichi Sankyo Co., Ltd.; Financial Interests, Institutional, Invited Speaker: Astellas Pharma Inc., Novartis Pharma K.K., Amgen inc., Ono Pharmaceutical Co., Ltd., MSD Co., Ltd., AstraZeneca K.K., Incyte Biosciences Japan G.K.; Financial Interests, Institutional, Research Grant: Pfizer Inc. All other authors have declared no conflicts of interest.