Lefitolimod vs standard of care (SOC) for patients with metastatic colorectal cancer (mCRC) responding to first-line standard treatment: Results from the randomized phase III IMPALA trial

PURPOSE: To study how adding oxaliplatin (l-OHP) to chronomodulated fluorouracil (5-FU)–leucovorin (LV) affected the objective response rate, as first-line treatment of metastatic colorectal cancer. PATIENTS AND METHODS: Two hundred patients from 15 institutions in four countries were randomly assigned to receive a 5-day course of chronomodulated 5-FU and LV (700 and 300 mg/m2/d, respectively; peak delivery rate at 0400 hours) with or without l-OHP on the first day of each course (125 mg/m2, as a 6-hour infusion). Each course was repeated every 21 days. Response was assessed by extramural review of computed tomography scans. RESULTS: Grade 3 to 4 toxicity from 5-FU–LV occurred in ≤ 5% of the patients (≤ 1% of the courses). Grade 3 to 4 diarrhea occurred in 43% of the patients given l-OHP (10% of the courses), and less than 2% of the patients had severe hematotoxicity. Thirteen percent of the patients had moderate functional impairment from peripheral sensory neuropathy. Sixteen percent of the patients receiving 5-FU–LV had an objective response (95% confidence interval [CI], 9% to 24%), compared with 53% of those receiving additional l-OHP (95% CI, 42% to 63%) (P < .001). The median progression-free survival time was 6.1 months with 5-FU–LV (range, 4.1 to 7.4 months) and 8.7 months (7.4 to 9.2 months) with l-OHP and 5-FU–LV (P = .048). Median survival times were 19.9 and 19.4 months, respectively. CONCLUSION: By chronomodulating 5-FU–LV, we were able to add l-OHP without compromising dose-intensities. l-OHP significantly improved the antitumor efficacy of this regimen.

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Phase III randomized trial comparing systemic versus intra-arterial oxaliplatin, combined with LV5FU2 +/- irinotecan and a targeted therapy, in the first-line treatment of metastatic colorectal cancer restricted to the liver (OSCAR): PRODIGE 49

Digestive and Liver Disease ◽

10.1016/j.dld.2021.12.012 ◽

2022 ◽

Author(s):

Simon Pernot ◽

Olivier Pellerin ◽

Laurent Mineur ◽

Carole Monterymard ◽

Denis Smith ◽

...

Keyword(s):

Colorectal Cancer ◽

Targeted Therapy ◽

Metastatic Colorectal Cancer ◽

Randomized Trial ◽

Phase Iii ◽

Line Treatment ◽

First Line ◽

First Line Treatment

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P-247 Real-world clinical outcomes for third-line standard of care regimens in deficient mismatch repair or microsatellite instability-high metastatic colorectal cancer in France

Annals of Oncology ◽

10.1016/j.annonc.2020.04.329 ◽

2020 ◽

Vol 31 ◽

pp. S170-S171

Author(s):

R. Cohen ◽

T. André ◽

M. Roset ◽

M. Amonkar ◽

P. Renna ◽

...

Keyword(s):

Colorectal Cancer ◽

Microsatellite Instability ◽

Metastatic Colorectal Cancer ◽

Mismatch Repair ◽

Clinical Outcomes ◽

Real World ◽

Standard Of Care ◽

Third Line ◽

Deficient Mismatch Repair ◽

Line Standard

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KRAS and BRAF Mutations as Prognostic and Predictive Biomarkers for Standard Chemotherapy Response in Metastatic Colorectal Cancer: A Single Institutional Study

Cells ◽

10.3390/cells9010219 ◽

2020 ◽

Vol 9 (1) ◽

pp. 219 ◽

Cited By ~ 3

Author(s):

Nuria Garcia-Carbonero ◽

Javier Martinez-Useros ◽

Weiyao Li ◽

Alberto Orta ◽

Nuria Perez ◽

...

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Predictive Biomarkers ◽

Braf V600e ◽

Chemotherapy Response ◽

First Line ◽

Standard Chemotherapy ◽

Braf Mutations ◽

Kras Mutations ◽

Line Standard

KRAS mutation is a confirmed predictive biomarker for anti-EGFR monoclonal antibody therapy response for metastatic colorectal cancer. However, its prognosis impact and the predictive potential for first-line standard chemotherapy remains unclear. On the other hand, V600E mutation is the most frequent and studied mutation in the BRAF gene, and it has been associated with a poor outcome of patients and a low response to anti-EGFR treatment. Thus, the aim of this study is to evaluate the role of KRAS and BRAF mutations as prognosis factors and predictive biomarkers for 1st line standard chemotherapy in metastatic colorectal cancer. KRAS mutations and BRAF V600E mutations exhibited a poor outcome (p = 0.021 and p < 0.0001, respectively). Cox multivariate analysis showed that the presence of liver metastasis (HR = 1.595; 95% CI: 1.086–2.343; p = 0.017), KRAS mutation (HR = 1.643; 95% CI: 1.110–2.431; p = 0.013) and BRAF V600E mutation (HR = 5.861; 95% CI: 2.531–13.570; p < 0.0001) were statistically significant co-variables for progression-free survival. Interestingly, patients with KRAS mutations were associated with a poor response to first line standard chemotherapy (p = 0.008). In contrast, the BRAF V600E mutation did not have any impact on the first line standard chemotherapy response (p = 0.540). Therefore, in the present study, we provide new insight on the role of KRAS and BRAF, not only as prognosis biomarkers, but also as first line standard chemotherapy response biomarkers in metastatic colorectal cancer.

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