ASCO GI 焦点派对丨林小燕教授、江涛教授剖析RAS野生型转移性结直肠癌抗EGFR治疗两项研究新进展

主任医师 博士生导师

博士 福建医科大学附属协和医院肿瘤内科 主治医师

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摘要号：17

Background:The DEEPER trial (NCT02515734), which evaluated mFOLFOXIRI (irinotecan 150 mg/m2, oxaliplatin 85 mg/m2, 5-FU 2400 mg/m2) plus cetuximab (cet) vs. bevacizumab (bev) as initial therapy in terms of depth of response (DpR) as the primary endpoint in RAS wild-type metastatic colorectal cancer (mCRC), has demonstrated a significantly better DpR in the cet arm (ASCO 2021). Moreover, favorable progression-free survival (PFS) was reported in the cet arm for patients (pts) with RAS/BRAF wild-type and left-sided tumors (ESMO 2023). Due to the small number of overall survival (OS) events, it was decided to extend the observation period, and the final survival analysis was performed at the cutoff date of August 2024.

Methods:Survival analysis was pre-planned in the per-protocol set (PPS), which consisted of pts evaluable for the DpR by an external review board. The clinical outcomes were evaluated according to clinical factors including primary tumor sidedness, liver metastasis status, and BRAF status using a log-rank test. All statistical tests were two-sided, and P values ≤ 0.05 were considered significant.

Results:321 of 359 enrolled pts were defined as PPS (median age 65 years, 64% male, performance status [PS] 0/1: 91%/9%, left/right primary: 84%/16%). In RAS wild-type and left-sided tumors, median PFS and OS were 13.9 months vs. 12.1 months (HR 0.81, 95% CI 0.63-1.05) and 45.3 months vs. 41.9 months (HR 0.85, 95% CI 0.64-1.12) in the cet vs. bev arm, respectively. BRAF status was available in 234 (73%) of the 321 pts in the PPS. An exploratory analysis showed that PFS was significantly better in the cet arm compared to the bev arm (median 14.8 months vs. 11.9 months, HR 0.71, 95% CI 0.52-0.97) in 178 pts with RAS/BRAF wild-type and left-sided tumors. Additionally, OS was 50.2 months vs. 40.2 months (HR 0.74, 95% CI 0.53-1.05). Moreover, according to liver disease status, mFOLFOXIRI plus cet was associated with longer PFS and OS in pts with RAS/BRAF wild-type and left-sided mCRC with extra-hepatic metastases (median 15.1 months vs. 11.4 months, HR 0.66, 95% CI 0.46-0.95 and 50.2 months vs. 38.6 months, HR 0.60, 95% CI 0.40-0.90), but not liver-limited disease (median 14.5 months vs. 15.5 months, HR 0.79, 95% CI 0.44-1.42 and 52.2 months vs. 49.9 months, HR 1.17, 95% CI 0.61-2.24).

Conclusions:The final survival analysis of the DEEPER trial demonstrated favorable PFS and OS with mFOLFOXIRI plus cet in pts with RAS/BRAF wild-type and left-sided mCRC. The mFOLFOXIRI plus cet regimen may be a good option for initial therapy, offering longer survival times in pts with extra-hepatic metastases.

摘要号：86

Background:

Anti-epidermal growth factor receptor monoclonal antibodies (anti-EGFR mAbs) are recommended as a first-line treatment in RAS wild-type (RASwt) left-sided metastatic colorectal cancer (mCRC). However, the efficacy of these therapies across different treatment lines remains unclear. This study aims to evaluate the efficacy of anti-EGFR mAb across first, second, third, and later-line treatments.

Methods:

We conducted a retrospective analysis of patients diagnosed with RASwt mCRC who received anti-EGFR mAb in all treatment lines at Siriraj Hospital between 2008 and 2023. The impact of anti-EGFR mAb treatment line on progression-free survival (PFS) and overall survival (OS) was determined using the Kaplan-Meier method and compared with the log-rank test.

Results:

Of the 350 patients with RASwt mCRC receiving anti-EGFR mAb, 33% (115 of 350) were treated in the first-line, while 16%, 45% and 6% were treated in the second-, third- and later-line settings, respectively. Eighty-six percent of patients had left-sided tumors, and anti-vascular growth factors were used in 34% of patients. The median follow-up time was 30.4 months (mo). Among patients with left-sided tumors, those receiving first-line anti-EGFR mAb treatment exhibited a significantly longer mPFS (11.9 mo, 95% CI 7.4-16.3, p<0.001). The mPFS in the second-, third- and later-line settings were 6.1 mo (95% CI 4.6-7.5), 4.9 mo (95% CI 3.8-6.0), and 5.1 mo (95% CI 2.3-7.9), respectively. There were no significant differences in terms of OS across treatment lines (p=0.27).

Conclusions:

Although first-line treatment with anti-EGFR mAb had the longest mPFS in left-sided mCRC, OS did not significantly differ among treatment lines. Therefore, anti-EGFR mAb can be incorporated as a part of therapy at any line of treatment.