| General information |
| Database: | DB00998 |
| Objective: | Mutations affecting RAS genes are now established predictive markers of nonresponse to antiEGFR antibodies in advanced CRC. This analysis assessed the prognostic and predictive impact of extended RAS and PIK3CA gene mutation status in patients receiving capecitabine plus or minus bevacizumab (¡Àmitomycin C) in the randomisedphase III MAX study. |
| Authors: | Price TJ, et al |
| Title: | Correlation of extended RAS and PIK3CA gene mutation status with outcomes from the phase III AGITG MAX STUDY involving capecitabine alone or in combination with bevacizumab plus or minus mitomycin C in advanced colorectal cancer. |
| Journal: | Br J Cancer. |
| Year: | 2015 |
| PMID: | 25742472 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | bevacizumab
|
| Target: | Vascular endothelial growth factor
|
| Cancer Type: | colorectal cancer |
| Cancer Subtype: | advanced colorectal cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | capecitabine + bevacizumab + minus mitomycin C |
| Study Type: | Correlation of extended RAS and PIKIIICA gene mutation status with outcomes from the phase III AGITG MAX STUDY |
| Key Patients Feature: | pts with advanced CRC |
| Biomarker: | RAS and PIK3CA gene mutation status |
| Biomark Analysis: | Extended RAS gene mutation status (WT vs MT) had no prognostic impact for PFS (HR 0.91 (0.711.17)) or OS (HR 0.95 (0.711.25)). The RAS gene mutation status was not predictive of the effectiveness of bevacizumab for PFS (HR 0.56 (0.370.85) for RAS MT and HR 0.69 (0.50.97) for RAS WT; P for interaction 0.50). The PIK3CA mutation was neither predictive for bevacizumab effect nor prognostic. |
| Control Group Info: | single arm |
| Treatment Info: | DNA was extracted from archival macrodissected formalinfixed paraffinembedded tumour tissue. Mutation status was determined using pyrosequencing, confirmed with Sanger sequencing (for equivocal RAS) and correlated with efficacy outcomes. |
| Primary End Point: | biomarker analysis |
| Secondary End Point: | NA |
| Patients Number: | 280 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 7.7 months among the patients with RAS MT tumours as compared with 7.6 months among those with RAS WT tumours (HR (RAS WT vs MT), 0.92; 95% CI, 0.71-1.17; P=0.49). 8.8 months among the patients with PIK3CA MT tumours as compared with 7.5 months among those with PIK3CA WT tumours (HR (PIK3CA WT vs MT), 0.90; 95% CI, 0.60-1.35; P=0.61). |
| Median OS A vs. C: | Among patients with RAS MT tumours, there was no statistical difference in OS, and the median OS was 22.8 months in the group receiving C and 20.4 months in the groups receiving CB or CBM (HR, 0.91; 95% CI, 0.58-1.44; P=0.70). Among patients with RAS WT tumours, the median OS was 20.6 months in the group receiving C and 18.9 months in the groups receiving CB or CBM (HR, 0.99; 95% CI, 0.67-1.45; P=0.95). Among patients with PIK3CA MT tumours, the median OS was 18.9 months in the group receiving C and 19.2 months in the groups receiving CB or CBM (HR, 1.18; 95% CI, 0.46-3.06; P=0.73). Among patients with PIK3CA WT tumours, the median OS was 20.6 months in the group receiving C and 19.8 months in the groups receiving CB or CBM (HR, 0.89; 95% CI, 0.65-1.22; P=0.47). |
| Adverse Event(agent arm): | NA |
| Conclusions: | Of KRAS exon 2 WT patients, 10% had additional RAS mutations. Neither all RAS gene mutation status nor PIK3CA mutation status was prognostic for PFS or OS, or predictive of bevacizumab outcome in patients with advanced CRC. |