A novel therapeutic strategy of personalized medicine based on anti-epidermal growth factor receptor monoclonal antibodies in patients with metastatic colorectal cancer

Abstract

Achieving tumor shrinkage may be a clinically relevant improvement in the treatment of metastatic colorectal cancer (mCRC). The present study attempted to evaluate early tumor shrinkage (ETS) and deepness of response over 6-8 courses of therapy, which were assessed previously in first-line trials of anti-epidermal growth factor receptor (EGFR) monoclonal antibodies. A total of 37 patients with mCRC that was considered unresectable or borderline resectable were enrolled in the study. Patients exhibited the wild-type RAS gene, and anti-EGFR monoclonal antibodies were used as the first-line treatment in the Department of Surgical Oncology at Gifu University School of Medicine (Gifu, Japan) between January 2010 and March 2017. Tumor shrinkage and other characteristics were evaluated according to the Response Evaluation Criteria In Solid Tumors (RECIST) classifications (version 1.1). The 3-year overall survival (OS) rate was >60.0% for all cases (n=37). The mean tumor shrinkage rate in the right side of the colon according to the RECIST classifications was -11.1%, whereas that for CRC on the left side showed a statistically significant difference at -54.0% (P=0.042). In addition, the rates of OS for stable disease + progressive disease compared with partial response + complete response, and those of OS for conversion therapy compared with non-conversion therapy were significantly different (both P<0.001). Carcinoembryonic antigen (CEA) was suggested to be a possible predictive factor for convalescence due to the 50% drop in its value after the 6-8 courses of therapy. Overall, the predictive performance of ETS with respect to PFS and OS is at least as good as the standard RECIST response, with the advantage of an earlier assessment, and this may improve convalescence, with CEA as a marker in support of ETS over a clinical treatment course. In RAS wild-type patients, it is important to evaluate the rate of tumor shrinkage from the beginning of the first-line treatment until 6-8 courses of anti-EGFR monoclonal antibodies have been administered.

Figure 1

Cumulative survival curves of all metastatic colorectal cancer cases (n=37). Overall survival of patients was calculated.

Figure 2

Cumulative survival curves showing the rates of overall survival between the patients with right-sided colon and those with left-sided colorectal cancer.

Figure 3

Mean tumor shrinkage rate in right-sided and left-sided colorectal cancer according to the classification of the Response Evaluation Criteria In Solid Tumors guidelines.

Figure 4

Cumulative survival curves showing the OS rates for patients with SD+PD compared with those with PR+CR. Differences were statistically significant (P<0.001). CR, complete response; PR, partial response; PD, progressive disease; SD, stable disease.

Figure 5

Cumulative survival curves. (A) The cumulative survival rate of the 29 patients with CR+PR was estimated to be −60.3%, whereas that in the 8 patients with stable disease + progressive disease was estimated to be −0.3%, indicating no shrinkage. (B) The cumulative survival rates for right-sided CRC (yellow) and left-sided CRC (purple). The results indicated that anti-EGFR monoclonal antibodies can be expected to result in an effect in right-sided CRC. CRC, colorectal cancer; EGFR, epidermal growth factor receptor.

Figure 5

Cumulative survival curves. (A) The cumulative survival rate of the 29 patients with CR+PR was estimated to be −60.3%, whereas that in the 8 patients with stable disease + progressive disease was estimated to be −0.3%, indicating no shrinkage. (B) The cumulative survival rates for right-sided CRC (yellow) and left-sided CRC (purple). The results indicated that anti-EGFR monoclonal antibodies can be expected to result in an effect in right-sided CRC. CRC, colorectal cancer; EGFR, epidermal growth factor receptor.

Figure 6

Cumulative survival curves showing the overall survival rates for conversion therapy compared with non-conversion therapy. Differences were statistically significant (P<0.001).

Figure 7

Cumulative survival curves showing that the 50% drop in CEA level suggest it to be a possible predictive factor for survival following 6–8 courses of therapy. CEA, carcinoembryonic antigen.

Figure 8

Cumulative survival curves showing the lack of a 50% drop in CA19-9, suggesting that it is not likely to be a possible predictive factor for survivor following 6–8 courses of therapy. CA19-9, carbohydrate antigen 19-9.

Figure 9

A novel treatment strategy in metastatic colorectal cancer cases indicating when conversion therapy (liver and lung) is possible. Cmab, cetuximab; Pmab, panitumumab; Bmab, bevacizumab; Rmab, ramucirumab; TFTD, TAS 102; PR, partial response; CPT-11, irinotecan.

Figure 10

A novel strategy in metastatic colorectal cancer cases indicating when conversion therapy (liver and lung) is not possible. BBP, bevacizumab beyond progression; Cmab, cetuximab; Pmab, panitumumab; Bmab, bevacizumab; Rmab, ramucirumab; TFTD, TAS 102; SD, stable disease; CPT-11, irinotecan; IRIS, TS-1 + irinotecan.