PD-031 An exploratory study-level meta-analysis assessing the impact of early tumour shrinkage on overall survival in patients with RAS wild-type metastatic colorectal cancer receiving first-line treatment in three randomised panitumumab trials

Purpose The addition of cetuximab to irinotecan, fluorouracil, and leucovorin (FOLFIRI) as first-line treatment for metastatic colorectal cancer (mCRC) was shown to reduce the risk of disease progression and increase the chance of response in patients with KRAS wild-type disease. An updated survival analysis, including additional patients analyzed for tumor mutation status, was undertaken. Patients and Methods Patients were randomly assigned to receive FOLFIRI with or without cetuximab. DNA was extracted from additional slide-mounted tumor samples previously used to assess epidermal growth factor receptor expression. Clinical outcome according to the tumor mutation status of KRAS and BRAF was assessed in the expanded patient series. Results The ascertainment rate of patients analyzed for tumor KRAS status was increased from 45% to 89%, with mutations detected in 37% of tumors. The addition of cetuximab to FOLFIRI in patients with KRAS wild-type disease resulted in significant improvements in overall survival (median, 23.5 v 20.0 months; hazard ratio [HR], 0.796; P = .0093), progression-free survival (median, 9.9 v 8.4 months; HR, 0.696; P = .0012), and response (rate 57.3% v 39.7%; odds ratio, 2.069; P < .001) compared with FOLFIRI alone. Significant interactions between KRAS status and treatment effect were noted for all key efficacy end points. KRAS mutation status was confirmed as a powerful predictive biomarker for the efficacy of cetuximab plus FOLFIRI. BRAF tumor mutation was a strong indicator of poor prognosis. Conclusion The addition of cetuximab to FOLFIRI as first-line therapy improves survival in patients with KRAS wild-type mCRC. BRAF tumor mutation is an indicator of poor prognosis.

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P-52 Overall survival with cetuximab every 2 weeks vs standard once-weekly administration schedule for first-line treatment of RAS wild-type metastatic colorectal cancer in patients with left- and right-sided primary tumor location

Annals of Oncology ◽

10.1016/j.annonc.2021.05.107 ◽

2021 ◽

Vol 32 ◽

pp. S114

Author(s):

S. Kasper ◽

A. Cheng ◽

M. Rouyer ◽

C. Foch ◽

F. Lamy ◽

...

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Tumor Location ◽

Line Treatment ◽

Wild Type ◽

First Line ◽

Weekly Administration ◽

Primary Tumor Location ◽

Left And Right ◽

First Line Treatment

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Is oxaliplatin a good partner for EGFR monoclonal antibodies as first-line treatment in KRAS wild-type metastatic colorectal cancer? A meta-analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e14645 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e14645-e14645

Author(s):

Feng Wen ◽

Qiu Li ◽

Ruilei Tang ◽

Yaxiong Sang ◽

Meng Li ◽

...

Keyword(s):

Colorectal Cancer ◽

Monoclonal Antibodies ◽

Metastatic Colorectal Cancer ◽

Response Rate ◽

Meta Analysis ◽

Fixed Effect ◽

Line Treatment ◽

Wild Type ◽

First Line ◽

First Line Treatment

e14645 Background: This meta-analysis was performed to determine whether the addition of monoclonal antibodies (mAbs) of epidermal growth factor receptor (EGFR) to oxaliplatin-based chemotherapy treatment improves efficacy in KRAS wild-type metastatic colorectal cancer (mCRC), and whether infusional 5-fluorouracil (5-FU) and oxaliplatin is a preferred combination for EGFR mAbs. Methods: Oxaliplatin (including treatment), EGFR mAbs, first-line treatment, KRAS wild-type, and mCRC were used as key words. The PRIME, OPUS, COIN, and NORDIC VII trials were identified by two independent authors. Time-to-event outcomes of overall survival (OS) and progression-free survival (PFS) were analyzed using HRs (Hazard Ratios) with fixed effect, and response rate (RR) using odd ratios (OR) with fixed effect. Results: A total of 1,767 patients who were KRAS wild-type were included in this meta-analysis, with 866 patients in the mAbs and chemotherapy combination group and 901 patients in the chemotherapy alone group. The addition of mAbs to oxaliplatin-based chemotherapy in patients with KRAS wild-type mCRC as first-line treatment resulted in significant improvements in PFS (HR=0.88; 95% confidence interval (CI), 0.79 to 0.99; P=0.03) and response rate (RR) (OR = 1.38; 95% CI, 1.14 to 1.66; P = 0.009) compared with chemotherapy alone, but the difference in OS was not significant (HR=0.96; 95% CI, 0.85 to 1.08; P=0.48). However, the differences neither in OS nor in PFS were not significant when mAbs were added to bolus 5-FU or capecitabine-based regimens compared with chemotherapy alone, whereas PFS improved with an infusional 5-FU and oxaliplatin combination (P=0.06; PFS, HR=0.76; 95% CI, 0.65 to 0.86; P=0.0002), and even OS was marginally significant. Conclusions: Oxaliplatin and infusional 5-FU regimen tends to be a better backbone combination with EGFR mAbs as first-line treatment in KRAS wild-type mCRC.

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