Rechallenge with Anti-EGFR Therapy in Metastatic Colorectal Cancer (mCRC): Results from South Australia mCRC Registry.

BACKGROUND: Anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (cetuximab or panitumumab) are today increasingly used in the first- or second-line setting for RAS wild-type metastatic colorectal cancer (CRC) patients. Following progression beyond third- or fourth-line therapy, some patients are unsuitable for further chemotherapy because of poor performance status or patient choice. However, a significant number of patients are still candidates for further therapy despite limited standard options being available. The role of rechallenge with anti-EGFR therapy, particularly in patients who had previously responded, is often considered, but there is limited evidence in the literature to support such a strategy. OBJECTIVE: This retrospective study aims to review the outcome of metastatic CRC patients who had anti-EGFR rechallenge. PATIENTS AND METHODS: Patients who had been rechallenged with anti-EGFR therapy were identified from the South Australian metastatic CRC database. Patient characteristics were recorded and tumor response was retrospectively assessed using Response Evaluation Criteria in Solid Tumors (RECIST). Kaplan-Meier analysis was used to assess progression free survival (PFS) for each rechallenge and overall survival (OS). RESULTS: Twenty-two patients were eligible for inclusion in this analysis. Disease control rate (stable disease and partial response) was 45.4% (ten patients) for patients who received rechallenge anti-EGFR. Seven patients received a second rechallenge and disease control rate was 28.6% (two patients). The median interval time between initial anti-EGFR therapy and rechallenge was 13.5 months. The median PFS after rechallenge 1 was 4.1 months and after rechallenge 2 was 3.5 months. The median OS was 7.7 months from date of rechallenge. CONCLUSIONS: Anti-EGFR rechallenge provides clinical benefit in patients with RAS wild-type metastatic CRC.

Outcomes for Metastatic Colorectal Cancer Based on Microsatellite Instability: Results from the South Australian Metastatic Colorectal Cancer Registry.

BACKGROUND: Microsatellite instability (MSI) is the molecular marker for DNA mismatch repair deficiency (dMMR) in colorectal cancer (CRC) and has been associated with better survival outcomes in early stage disease. In metastatic CRC (mCRC), outcomes for patients with MSI are less clear. There is evolving evidence that treatment pathways for MSI CRC should include programmed-death 1 (PD-1) antibodies. OBJECTIVE: An analysis was performed to explore the impact of MSI status on overall survival (OS) in mCRC. PATIENTS AND METHODS: South Australian Metastatic CRC Registry data were analysed to assess patient characteristics and survival outcomes, comparing patients with MSI CRC with those whose tumours were microsatellite stable (MSS). Kaplan-Meier survival analysis was used to assess OS. Cox regression analysis was undertaken to assess the independence of MSI as a prognostic factor. RESULTS: Of 4359 patients registered on the database, 598 (14%) had been tested for, and 62 (10.1%) of these patients had, demonstrable MSI. There were significantly higher rates of right-sided primary (p < 0.001), poorly differentiated pathology (p = 0.002), and BRAF V600E mutation (p < 0.001) in the MSI group. The MSI group were also less likely to receive chemotherapy (p < 0.001) or to have liver surgery, but more likely to be diagnosed at an early stage. The median overall survival was 9.5 months for those with MSI CRC versus 21.3 months for MSS CRC patients (p = 0.052). Cox regression analysis indicated that MSI was not an independent predictor of OS. Independent predictors of better OS included having liver surgery for metastasis, having chemotherapy, and being initially diagnosed at an early stage. CONCLUSIONS: Only 14% of patients with mCRC were tested for MSI, and 1 in 10 were found to be MSI high. The clinical characteristics of MSI mCRC are in keeping with those previously reported. MSI in this population-based registry was associated with a numerically lower survival which did not attain statistical significance.

Capecitabine in locally advanced anal cancer, do we need randomised evidence?

INTRODUCTION: Standard treatment for locally advanced anal cancer is chemoradiotherapy with mitomycin C and fluorouracil. However, infusional fluorouracil requires central venous catheter placement potentiating risk of infection and thrombosis. Capecitabine which is an oral tumor activated fluoropyrimidine carbamate is an established treatment alternative to infusional fluorouracil for patients with gastrointestinal cancers. Areas covered: This review examines and discusses the current evidence for substitution of Capecitabine for infusional fluorouracil in locally advanced anal cancer. Two phase II studies, one phase I study and three retrospective reviews were identified. The rate of complete response and locoregional control with the use of Capecitabine in all of these studies ranged from 77% to 89.1% and 79% to 94% respectively, and these results are comparable with prior pivotal studies. The main toxicity with radiation and Capecitabine is radiation dermatitis occurring in 23% to 63% of patients. Despite high rates of radiation dermatitis, treatment completion rates were high, suggesting that it is a well tolerated protocol. Expert commentary: Capecitabine has been used widely in other gastrointestinal cancers, including rectal cancer in chemo-radiotherapy protocols, with proven efficacy and safety and could be a reasonable treatment alternative to fluorouracil in locally advanced anal cancer.

Selective internal radiation therapy for liver metastases from colorectal cancer.

Liver metastases are often the dominant site of metastatic disease in colorectal cancer. Selective internal radiation therapy (SIRT) involves embolising radiolabeled spheres (SIR-Spheres) into the arterial supply of the liver. This review assesses the effectiveness and toxicity of SIRT in the treatment of metastatic colorectal cancer liver metastasis when given alone or with systemic or regional hepatic artery chemotherapy. We reviewed only randomised controlled trials comparing SIRT and chemotherapy (systemic and/or regional) with chemotherapy alone, or comparing SIRT alone with best supportive care. Only four randomized trials were identified. Due to heterogeneity of the patients and treatments received it was not possible to perform a formal meta-analysis, therefore this is a descriptive analysis only. All studies included patients with either liver only or liver dominant metastatic colorectal cancer. Two trials compared SIRT alone and SIRT with chemotherapy first line. The first with only 21 patients revealed a significant improvement in PFS and median survival with SIRT. The larger second study SIRFLOX of 530 patients comparing SIRT and current standard first line FOLFOX chemotherapy (+/- bevacizumab) with standard FOLFOX+/-bevacizumab alone. There was no improvement in overall PFS with addition of SIRT. In chemotherapy refractory patients SIRT and systemic chemotherapy (fluorouracil) improved progression free survival but not overall survival. A final study (63 patients) compared SIRT and regional chemotherapy (floxuridine) with regional chemotherapy alone in first line showed no significant difference in progression free survival and median survival. There remains a lack of evidence that SIRT improves survival or quality of life in patients with metastatic colorectal cancer. The overall survival results from SIRFLOX combined with FOXFIRE and FOXFIRE Global are awaited.