Prognostic Differences of RAS Mutations: Results from the South Australian Metastatic Colorectal Registry.

BACKGROUND: Effective targeting of RAS mutations has proven elusive until recently. Novel agents directly targeting KRAS G12C have shown promise in early-phase clinical trials that included patients with metastatic colorectal cancer. Prior reports have suggested that G12C mutation may be predictive of poor outcome. OBJECTIVE: Assessment of the specific characteristics and prognostic implications of individual RAS mutation subtypes in patients with metastatic colorectal cancer. PATIENTS AND METHODS: Retrospective review of individual RAS mutation types from the South Australian Metastatic Colorectal Registry between 2006 and 2020. RESULTS: Of the 5165 patients entered onto the registry, 2305 (45%) had RAS mutation results available. 772 (33%) had a RAS mutation. The nature of the RAS mutation was available in 668 (87% of those with RAS mutation). Rare mutations (outside codons 12 and 13) made up 12.6% of the total. There were numerical differences in survival between the specific RAS mutation subgroups, with the longest median overall survival (30 months) observed in those with G12S mutations. However, there was no statistical difference in survival when comparing the various RAS mutations, including the comparison of G12C to G12S (p = 0.38). Patients with cancer harbouring rare RAS mutations had a median survival of 30 months. CONCLUSIONS: Whilst the G12S mutation was associated with the longest survival numerically, the observed survival for patients with the most common RAS mutations (G12C, G12V, G12A, G12D and G13D) did not significantly differ.

Regorafenib outcomes from the population based South Australian Metastatic Colorectal Cancer Registry.

AIM: Reviewing outcomes of regorafenib use in metastatic colorectal cancer using real-world data from the South Australian Metastatic Colorectal Cancer Registry. METHODS: A retrospective review of the characteristics and outcomes of patients who received regorafenib in the Registry up to December 2018. The registry started in February 2006. RESULTS: Fifty-three patients received regorafenib therapy since approved by the therapeutic goods administration in November 2013. The median age was 66 (range 34-82). 66% were male, 66% had stage IV disease at diagnosis, 53% had liver only involvement, whereas 13% had liver and lung disease and 6% had lung only involvement. 75% had left-sided primary. KRAS was available in 35/53 patients with 49% of them being WT. BRAF status was known in 8/53 with 25% of them having a mutated variant. MSI testing was known in 14 patients in whom 21% of them had MSI-High tumors. Prior lines of treatment received: one line 4%, two 9%, three 23%, four 26%, >four 37%. Prior biological use: bevacizumab 72%, anti-EGFR 100% (for RAS WT). Median survival from diagnosis was 3.3 years (95% CI, 2.8-3.8 years). Median survival from the start of regorafenib was 7.1 months (95% CI, 4.8-9.4 months) and the 12-month survival rate was 28%. CONCLUSION: The survival outcome for those patients from our population-based registry who access regorafenib is in keeping with reports from large, randomized trials. Thus, clinicians can quote local real world data when discussing efficacy and access to regorafenib therapy for mCRC patients.

Curative therapy for rectal cancer.

Introduction: A comprehensive trimodality approach has become the standard of care for patients with locally advanced rectal cancer. However, the sequencing and duration of chemotherapy and chemoradiotherapy around surgery varies between clinical studies and geographical regions. Growing evidence is also mounting for strategies such as total neoadjuvant therapy and non-operative management for carefully selected patients.Areas covered: We provide a perspective review of the current evidence and controversies in the treatment of locally advanced rectal cancer including the recent updates from the 2020 ASCO annual conference.Expert opinion: With ongoing advances in the management of locally advanced rectal cancer, a multidisciplinary team approach is necessary as treatments could involve multiple approaches. Chemoradiotherapy whether short or long course followed by at least 3 months of systemic chemotherapy may be the preferred option to balance local and distant disease control. Albeit the choice of doublet or triplet chemotherapy is still controversial. As total neoadjuvant treatment becomes part of the standard of care in rectal cancer, modification of the surveillance schedule is needed to detect early recurrences which may be limited by resources and availability of services.