Pathological responses after angiogenesis or EGFR inhibitors in metastatic colorectal cancer depend on the chemotherapy backbone

Abstract

Background:Optimal preoperative treatment before colorectal cancer metastases (CRCM) resection remains unclear. This study evaluated pathological responses (pR) in CRCM resected after chemotherapy alone or combined with angiogenesis or epidermal growth factor receptor (EGFR) inhibitors.Methods:Pathological response was retrospectively evaluated on 264 resected metastases from 99 patients. The proportion of responding metastases after different preoperative treatments was reported and compared. Patient's progression-free survival (PFS) and overall survival (OS) were compared based on pR.Results:The combination of anti-angiogenics with oxaliplatin-based chemotherapy resulted in more pR than when they were combined with irinotecan-based chemotherapy (80% vs 50% P<0.001). Inversely, the combination of EGFR inhibitors with oxaliplatin-based chemotherapy seemed to induce fewer pR than when they were combined with irinotecan-based treatment (53% vs 72% P=0.049). Overall survival at 5 years was improved for patients with a pR in all resected metastases compared with those who did not achieve a pR (68.5% vs 32.6% P=0.023) and this response was the only factor predicting OS in a multivariate analysis.Conclusion:The chemotherapy partner combined with angiogenesis or EGFR inhibitors influenced pR in resected CRCM. In our exploratory analysis anti-angiogenic/oxaliplatin-based regimens and anti-EGFR/irinotecan-based regimens were associated with the highest pR. Prospective randomised trials should be performed to validate these observations.

Pathologic response after preoperative therapy predicts prognosis of Chinese colorectal cancer patients with liver metastases

“…In the present study, the addition of bevacizumab or cetuximab did not result in a significant difference in pathologic response rates for the whole metastases cohort, but these drugs did have an effect when certain chemotherapy backbones were implemented. These results were in agreement with those of most studies that found that the addition of targeted therapy, including bevacizumab and cetuximab, probably has an effect on the pathologic response of colorectal cancer and liver metastases; however, the effect depended on the chemotherapy backbone [ 17 , 25 , 26 , 30 ]. In the present study, for metastases treated with irinotecan-based chemotherapy, the addition of either bevacizumab or cetuximab resulted in higher pathologic response rates than chemotherapy alone.…”

“…In the present study, for metastases treated with irinotecan-based chemotherapy, the addition of either bevacizumab or cetuximab resulted in higher pathologic response rates than chemotherapy alone. This confirmed the finding of Carrasco et al [ 25 ] that anti-epidermal growth factor receptor agents combined with irinotecan-based regimens were associated with higher pathologic response rates and further supplemented the advantage of bevacizumab/irinotecan-based regimens. In contrast, for metastases treated with oxaliplatin-based chemotherapy, the addition of bevacizumab led to a pathologic response rate similar to that in the chemotherapy-alone subgroup but led to a higher pathologic response rate than that in the cetuximab-combined chemotherapy subgroup.…”

“…This result was in accordance with the results found in the cetuximab subgroup, in which cetuximab/irinotecan-based chemotherapy resulted in a higher pathologic response rate than the cetuximab/oxaliplatin-based combination. This finding is also supported by previously reported results that cetuximab/oxaliplatin-based regimens were probably not a good choice in terms of pathologic response rate for the treatment of colorectal cancer with liver metastases [ 25 , 26 ]. However, considering the relatively small sample sizes of the targeted therapy groups in the present study, the results should be interpreted with caution.…”

Optimal Sequences and Combination of Chemotherapy and Monoclonal Antibodies in the Treatment of Patients With Metastatic Colorectal Cancer

“…Было выявлено, что наи-большая частота выраженных патоморфологических эффектов достигалась при сочетании анти-EGFR антител с иринотекан-содержащими режимами химиотерапии: 55 % против 6 % при комбинациях с оксалиплатином, а также бевацизумаба с оксалиплатин-содержащими схемами: 60 % против 17 % при сочетании с иринотека-ном. Однако следует помнить, что исследование носило ретроспективный характер [18].…”

Use of Bevacizumab in the Management of Potentially Resectable Colorectal Liver Metastases: Safety, Pathologic Assessment and Benefit

“…Pooling data from these studies estimated that bevacizumab addition increased the occurrence of complete pathologic response by 3.9 %, from 7.8 % with chemotherapy alone to 11.7 % with combined regimen. Although the relevance of the cytotoxic backbone added to preoperative bevacizumab is yet unclear, recent data seem to indicate that the optimization of the associated regimen could impact bevacizumab-induced increase in pathologic response rate [47]. Moreover, bevacizumab had been shown to improve the degree of pathological response [48], and to induce an unusual, infarct-like necrosis [49]; both conditions have been reported to be associated with better prognosis [18].…”