Impact of Primary Tumor Location and Early Regression on Survival in Patients with Metastatic CRC

Methodology of the Analysis

In the single-arm phase II clinical trial, patients with mCRC were given a first-line treatment combining FOLFIRI chemotherapy (5-fluorouracil, leucovorin, irinotecan) and panitumumab (at a dose of 6 mg/kg) at 2-week intervals until disease progression. The retrospective analysis included patients from this study who were confirmed to be RAS wild-type (wt-RAS). The primary tumor location data were obtained from surgical protocols or pathology reports. Tumors located from the cecum to the transverse colon were classified as right-sided, and tumors from the splenic flexure to the rectum were classified as left-sided. 

Data from imaging methods (CT or MRI) were used to evaluate ETS and disease progression. The influence of tumor location on ETS, objective response rate (ORR), progression-free survival (PFS), and resection rates were statistically analyzed. ETS was defined as a reduction in the sum of the largest diameters of tumor lesions by ≥ 30% within the first 8 weeks of treatment. The impact of ETS on PFS and ORR was also analyzed.

Results

For the 69 patients included in the assessment, the absence of RAS mutations (wt-RAS) was confirmed, with 9 of them also confirmed to have BRAF mutations. The primary tumor location was known for 52 of these patients. Forty-five of them (87%) had left-sided tumors. The median PFS for patients with left-sided tumors was longer than for those with right-sided tumors (11.2 vs. 7.2 months, hazard ratio [HR] 1.45; 95% confidence interval [CI] 0.56–3.77). Patients with left-sided tumors more often achieved ETS (53 vs. 29%). ORR and resection rates did not significantly differ between the analyzed groups. Achieving ETS was associated with longer PFS regardless of the primary tumor location (left-sided tumors: HR 0.53; 95% CI 0.22–1.29; right-sided tumors: HR 0.35; 95% CI 0.03–3.54). 

Conclusion

This analysis confirmed the prognostic significance of primary tumor location on the outcomes of patients with mCRC who received a first-line treatment combination of panitumumab and the FOLFIRI chemotherapy regimen. ETS ≥ 30% was associated with longer PFS and better treatment responses regardless of the primary tumor location. These results suggest that ETS could help identify a subset of patients with right-sided CRC who have the potential to respond well to panitumumab therapy. 

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Source: Köhne C.-H., Karthaus M., Mineur L. et al. Impact of primary tumour location and early tumour shrinkage on outcomes in patients with RAS wild-type metastatic colorectal cancer following first-line FOLFIRI plus panitumumab. Drugs R&D 2019; 19 (3): 267–275, doi: 10.1007/s40268-019-0278-8.