Treatment Of Recurrent And Advanced Colorectal Cancer Research Articles

P-187 Epidermal growth factor receptor inhibitors (EGFRi) in patients with left-side, RAS wildtype metastatic colorectal cancer: Clinician use and outcomes for patients

Current treatment for metastatic colorectal cancer (mCRC), includes anti-epidermal growth factor receptor inhibitors (EGFRi) for RAS wildtype cancers. With improved outcomes has come added complexity for clinician treatment selection and sequencing. Head-to-head studies support first-line EGFRi use over bevacizumab in combination with chemotherapy for patients with a left-side primary. In January 2015, the EGFRi cetuximab gained government approval for first-line use in Australia, with routine RAS testing increasing in turn. In clinical practice, around 50% of patients do not receive second-line treatment, suggesting many patients miss out on this treatment option if reserved for second-line and later treatment. Clinical data from July 2009 to July 2021 was reviewed from TRACC (Treatment of Recurrent and Advanced Colorectal Cancer), a prospective, comprehensive, multi-site Australasian registry, to identify patients with RAS wildtype, left-side primary mCRC who received first-line treatment. Intent (curative vs palliative), biologic use and chemotherapy backbone were described over time. Patients who received first-line palliative intent doublet chemotherapy who were ECOG 0 or 1 at diagnosis were further characterised. Second-line treatment groups were analysed according to biologic and sequence used. Fisher’s exact test was used for significance tests and Kaplan Meier curves for survival analyses. 800 patients had left-side primary RAS wildtype mCRC and received first-line chemotherapy. 166 (20%) received first-line EGFRi plus chemotherapy, 352 (43%) received bevacizumab plus chemotherapy, and 282 (35%) received chemotherapy alone. Patients diagnosed after government EGFRi approval in January 2015 were more likely to be treated with first-line EGFRi plus chemotherapy than first-line bevacizumab plus chemotherapy (36% vs 30%, p < 0.001). While patients receiving first-line EGFRi were younger (60 vs 62 years, p=0.006) with fewer comorbidities (Charlson Comorbidity Index ≥ 3 in 13% vs 20%, p=0.048), ECOG status, de novo metastatic disease, deficient mismatch repair status or site of metastases were not different between the two groups. Overall, 148 (19%) left-side primary RAS wildtype patients never received any biologic agent. Of the palliative intent cohort (n = 490), median progression-free survival (PFS) was 11.6, 10.5 and 9.2 months for EGFRi plus doublet chemotherapy, bevacizumab plus doublet chemotherapy, and doublet chemotherapy alone respectively. EGFRi plus doublet chemotherapy had significantly longer PFS than doublet chemotherapy alone (HR 0.70 [0.52 - 0.95], p=0.022), but did not reach statistical significance compared to the bevacizumab group. However, median overall survival for the palliative intent cohort was significantly improved in the EGFRi group compared to bevacizumab group (53.2 vs 30.0 months; HR 0.70 [0.52 – 0.95]). When sequencing agents at progression, second-line PFS trended longer for those receiving EGFRi then bevacizumab, as compared to those receiving bevacizumab then EGFRi (7.9 vs 6.0 months; p=0.25). In this community series, first-line EGFRi plus doublet chemotherapy significantly improved OS when compared with bevacizumab plus doublet chemotherapy for left-side RAS wildtype mCRC patients. This was despite not demonstrating a PFS benefit in first-line, suggesting treatment sequencing may impact biologic efficacy. Despite EGFRi use increasing over time, 1 in 5 patients with left-side RAS wildtype mCRC never received any biologic agent.

Long-term survival outcomes following resection of lung metastases (LM) from a colorectal primary.

50 Background: Liver metastatectomy in oligometastatic colorectal cancer (CRC) can result in long-term disease control1. The benefit of resecting LM is unclear, with good survival outcomes from medical therapy (MT) alone and a recent randomised controlled trial failed to demonstrate an overall survival (OS) benefit2. Methods: We examined TRACC (Treatment of Recurrent and Advanced Colorectal Cancer), a multisite registry for metastatic colorectal cancer (mCRC) patients (pts) from September 2002 – July 2021, focusing on the longer-term outcomes for pts with lung only metastatic disease (LOM). Key clinicopathological, treatment and outcome variables were analysed. Survival outcomes were determined by Kaplan-Meier method. Results: Of 3928 pts, 341 (8.7%) had LOM. The median OS was significantly improved for LOM vs. all mCRC pts (44.5 months vs. 24.8 months, p = &lt;0.0001). Of 341 LOM pts, 142 (42%) had lung resection (LRes),128 (38%) had MT, 71 (20%) best supportive care. Key clinicopathological characteristics are summarised in Table. OS was significantly longer for LRes vs. MT (3yrs-80.1% vs. 41.9%, p = &lt;0.0001, 5 yrs-65.2% vs. 21.1%, p = 0.0001). 10 yr survival for LRes was 50%, with no survivors from MT. The median palliative chemotherapy free interval was 13 months (95% CI 3.1 – 18.7) with recurrence after LRes/death. 20/142 (14%) of the LRes pts had recurrent LRes (median time to repeat resection of 11.4 months, median survival of 66.9 months from repeat LRes). Conclusions: LM from mCRC have an indolent course, with good survival outcomes with MT alone. LRes provides a clinically meaningful palliative chemotherapy free interval and long term survival in selected pts. Significant differences in prognostic factors may have contributed to the observed survival differences between LRes and MT. Reference Dexiang Z, Li R, Ye W, Haifu W, Yunshi Z, Qinghai y, Shenyong Z, Bo X, Li L, Xiangou P, Haohao L, Lehi Y, Tianshu L, Jia f, Xinyu Q, Jianmin X. Outcome of patients with colorectal liver metastasis: analysis of 1,613 consecutive cases. Ann Surg Oncol. 2012 Sep;19(9):2860-8. doi:10.1245/s10434-012-2356-9.Epub 2012 Apr 12. PMID: 22526903. Treasure, T., Farewell, V., Macbeth, F. et al. Pulmonary Metastatectomy versus Continued Active Monitoring in Colorectal Cancer (PulMiCC): a multicentre randomised clinical trial. Trials 20,718 (2019). https://doi.org/10.1186/s13063-019-3837-y [Table: see text]

Impact of the evolution in RAS mutation analysis in Australian patients with metastatic colorectal cancer.

RAS mutation testing now routinely informs the optimal management of metastatic colorectal cancer (mCRC), specifically the finding of a RAS mutation defines patients who will not benefit from treatment with an epidermal growth factor receptor inhibitor. Over time more RAS genes have been tested and more sensitive techniques used. To review routine care RAS testing and results over time. A retrospective analysis of the molecular data collected prospectively in the multi-site Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) registry from 2009 to 2018 was undertaken. Patients with RAS data were further analyzed. In parallel, the RAS mutation status of patients enrolled in the Test Tailor Treat (TTT) program was examined for 2011-2018. Of 2908 patients in the TRACC registry, 1892 (65%) were tested, with 898 (47%) of tested patients found to be RAS mutant (RASmt). RAS data were available for 5935 TTT patients. Of the tested TRACC patients diagnosed in 2009 and 2010, 38% were RASmt. For each 2-year period from 2011/2012 through to 2017/2018, the prevalence of RASmt in TRACC and TTT was 42% and 40% (2011/2012), 52% and 40% (2013/2014), 47% and 49% (2015/2016), and 47% and 49% (2017/2018). Based on both TRACC and TTT data, the proportion of patients reported to have a RAS mutation increased from 2009 to 2015 but has remained relatively stable in recent years. The increased proportion of RASmt patients observed over time is likely largely driven by the uptake of extended RAS testing.

Initial experience of TAS-102 chemotherapy in Australian patients with Chemo-refractory metastatic colorectal cancer

For patients with refractory metastatic colorectal cancer (mCRC) treatment with Trifluridine/Tipiracil, also known as TAS-102, improves overall survival. This study aims to investigate the efficacy and safety of TAS-102 in a real-world population from Victoria, Australia. A retrospective analysis of prospectively collected data from the Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) registry was undertaken. The characteristics and outcomes of patients receiving TAS-102 were assessed and compared to those enrolled in the registration study (RECOURSE).Across 13 sites, 107 patients were treated with TAS-102. The median age was 60 years (range: 31-83), compared to 63 for RECOURSE. Comparing registry TAS-102-treated and RECOURSE patients, 75% vs 100% were ECOG performance status 0-1, 74% vs 79% had initiated treatment more than 18 months from diagnosis of metastatic disease and 36% vs 49% were RAS wild-type. Median time on treatment was 10.4 weeks (range: 1.7-32). Median progression-free survival (PFS) was 3.3 months compared to 2 months in RECOURSE, while median overall survival was the same at 7.1 months. Two patients (2.3%) had febrile neutropenia and there were no treatment-related deaths, where TAS-102 dose at treatment initiation was at clinician discretion.TRACC registry patients treated with TAS-102 were younger than those from the RECOURSE trial, with similar overall survival observed. Less strict application of RECIST criteria and less frequent imaging may have contributed to an apparently longer PFS.

Patient demographics and management landscape of metastatic colorectal cancer in the third-line setting: Real-world data in an australian population.

Colorectal cancer is the third most common cancer and second leading cause of cancer mortality in Australia, thus carrying a significant disease burden. This analysis aims to explore real-world treatment landscape of metastatic colorectal cancer in the third-line setting. We retrospectively analysed treatment of recurrent and advanced colorectal cancer (TRACC) registry database from 2009 onwards. Patients treated with palliative intent who progressed after two lines of therapies were included. One treatment line was defined as any combination of systemic therapy given until progression. Out of 1820 patients treated palliatively, 32% (590 patients) met study criteria. Of these, 43% (254 patients) proceeded to third-line therapy, equating to 14% of all metastatic patients. In KRAS mutant or unknown tumours (97 patients), fluoropyrimidine (FP)-oxaliplatin combination was the most common choice (51%), followed by FP-irinotecan (15%), trifluridine/tipiracil (11%), mono-chemotherapy (10%), regorafenib (5%) and others (7%). Majority of FP-doublet (83%) was given as rechallenge. In 157 patients with KRAS wildtype disease, monotherapy with EGFR inhibitor was most commonly used (41%), followed by EGFR inhibitor with chemotherapy (20%), FP-doublet (18%), mono-chemotherapy (6%), trifluridine/tipiracil (6%), regorafenib (1%) and others (8%). Median overall survival was 7.1 months (range 0.4-41.2), and median time on third-line treatment was 3 months (range 0.1-40). In real-world Australian population, treatment choices differed based on KRAS status and will likely change with the availability of newer drugs on the pharmaceutical benefits scheme. Survival outcomes are comparable to newer agents in clinical trials for select patients.

Initial experience of TAS-102 chemotherapy in Australian patients with chemorefractory metastatic colorectal cancer.

71 Background: For patients with refractory metastatic colorectal cancer (mCRC) treatment with Trifluridine/Tipiracil, also known as TAS-102, improves overall survival. In Australia, TAS-102 was initially made available locally through patients self-funding, later via an industry sponsored Medicine Access Program (MAP) and then via the Pharmaceutical Benefits Scheme (PBS). This study aims to investigate the efficacy and safety of TAS-102 in real world Australian population. Methods: A retrospective analysis of prospectively collected data from the Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) registry was undertaken. The characteristics and outcomes of patients receiving TAS-102 were assessed and compared to all TRACC patients and those enrolled in the registration study (RECOURSE). Results: Across 13 sites, 107 patients were treated with TAS-102 (non-PBS n = 27, PBS n = 80), The median number of patients per site was 7 (range: 1-17). The median age was 60 years (range: 31-83), compared to 67 for all TRACC patients and 63 for RECOURSE. Comparing registry TAS-102 and RECOURSE patients, 75% vs 100% were ECOG performance status 0-1, 74% vs 79% had initiated treatment more than 18 months from diagnosis of metastatic disease and 39% vs 49% were RAS wild type. Median time on treatment was 10.4 weeks (range: 1.7-32). Median clinician assessed progression-free survival was 3.3 compared to RECIST defined PFS of 2 months in RECOURSE study, while median overall survival was the same at 7.1 months. Two patients (2.3%) had febrile neutropenia and there were no treatment-related deaths in the real-world series, where TAS102 dose at treatment initiation was at clinician discretion. In the RECOURSE study there was a 4% febrile neutropenia rate and one treatment-related death. Conclusions: TRACC registry patients treated with TAS102 were younger than both TRACC patients overall and those from the RECOURSE trial. Less strict application of RECIST criteria and less frequent imaging may have contributed to an apparently longer PFS. However overall survival outcomes achieved with TAS102 in real world patients were comparable to findings from this pivotal trial with an acceptable rate of major adverse events.

Outcomes of isolated distant lymph node metastases in colorectal cancer.

84 Background: The optimal management of isolated distant lymph node metastases (IDLNM) in metastatic colorectal cancer (mCRC) is not clearly established. Small case series and prior data from the TRACC (Treatment of Recurrent and Advanced Colorectal Cancer) registry support the use of radical treatment with curative intent (local resection, chemo-radiation or stereotactic radiotherapy), which may lead to better outcomes in mCRC patients with IDLNM. Aims: This study investigates the clinical characteristics and outcomes of mCRC patients with IDLNM treated with systemic therapies plus locoregional therapy with curative intent versus systemic therapies with palliative intent. Methods: Clinical data were collected and reviewed from the TRACC registry, a prospective, comprehensive registry for mCRC from multiple tertiary hospitals across Australia from 01/07/2009 to 30/06/2020. Clinicopathological characteristics, treatment modalities and survival outcomes were analyzed in patients with IDLNM and compared to patients with other organ metastases. Fisher exact test was used for significance tests and Kaplan Meier curves for survival analyses. Results: Of 3408 mCRC patients with a median follow-up of 38.0 months, 93 (2.7%) were found to have IDLNM. Compared to mCRC with other organ metastases, patients with IDLNM were younger (mean age: 62.1 vs 65.6 years, p=0.0200), more likely to have metachronous disease (57.0% vs 38.9%, p=0.0005), be KRAS wild-type (74.6% vs 53.9%, p=0.0012) and BRAF mutant (12.9% vs 6.2%, p=0.0100). There was no overall survival difference between with IDLNM and those with other organ metastases (median OS 27.24 vs 25.92 months, p=0.2300). Twenty-four patients (25.8%) with IDLNM received treatment with curative intent, with a trend towards improved overall survival compared to those with other organ metastases treated with curative intent (73.5 vs 62.7 months, p=0.8200). Amongst mCRC patients with IDLNM, those who received treatment with curative intent had a significantly better overall survival than those treated with palliative intent (73.5months vs 23.2 months, p=0.0070). Conclusions: Our findings suggest that there are differences in the patterns of presentation of IDLNM and other organ metastases. Radical treatment with curative intent options should be considered for mCRC patients with IDLNM where appropriate.

Health economic analysis of doublet chemotherapy with and without bevacizumab for first-line treatment of RAS mutant metastatic colorectal cancer based on real-world data.

e16048 Background: Bevacizumab remains the dominant biologic treatment option for RAS mutant (RASmt) metastatic colorectal cancer (mCRC). While the health economic impact of bevacizumab in the RASmt subpopulation may deviate from its use in the general mCRC population, this has never been investigated. This study uses the power of real-world data to assess the cost-effectiveness of doublet chemotherapy with compared to without bevacizumab (ChemBev and ChemOnly, respectively) for first-line treatment of RASmt mCRC, while accounting for subsequent treatment in second and third line. Methods: Data from the Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) registry was analyzed to populate a discrete event simulation of three treatment lines, surgery of primary tumor and metastases, hospitalizations following serious adverse events, and best supportive care. Imbalance in baseline patient and disease characteristics was corrected for in all analyses using inverse probability weights. Costs were included from an Australian public payer perspective in Australian dollars (AUD). All health and economic outcomes were discounted at 5% per year. Results: Of the 507 included RASmt mCRC patients that started first-line treatment in the 2010 – 2017 time period, 345 received ChemBev and 162 ChemOnly. The corrected median time on first-line treatment was 7.1 months (95% confidence interval: 6.4 – 8.0) for ChemBev and 4.1 months (3.5 – 5.1) for ChemOnly. Time on second- and third-line treatment was comparable between the groups. Corrected overall survival was 22.6 months (21.7 – 24.0) for ChemBev and 14.3 months (12.1 – 21.7) for ChemOnly. In terms of the health economic impact, mean life years were 1.9 for ChemBev and 1.5 for ChemOnly, and mean costs were AUD 93,025 and AUD 44,929 per patient, respectively. The resulting incremental cost-effectiveness ratio (ICER) of ChemBev compared to ChemOnly was AUD 149,317 per life-year gained (LYG). Conclusions: In contrast to results from clinical trials, overall survival was substantially longer for patients who received bevacizumab, which can possibly be attributed to an imbalance between groups despite correction for known prognostic factors. At an ICER of AUD 149,317 per LYG, the economic burden of upfront treatment with bevacizumab was found to be substantial and consistent with estimates for the general mCRC population. This is mainly caused by the duration of first-line treatment, which was significantly longer for ChemBev.

Use and impact of perioperative chemotherapy in patients with resectable colorectal cancer metastases.

159 Background: There is conflicting evidence regarding benefit of perioperative chemotherapy (p-chemo) for metastatic colorectal cancer (mCRC) patients (pts) undergoing resection of metastases (mets). Aims: To describe use of and outcomes from p-chemo in mCRC pts who underwent resection of isolated liver or lung mets. Methods: Pts were identified from the TRACC (Treatment of Recurrent and Advanced Colorectal Cancer) database, a multi-centre registry of mCRC pts. P-chemo was defined as chemotherapy within 12 weeks of surgery. Multivariate (MV) analysis using a Cox proportional hazards model was undertaken. Results: 371 pts were identified. Median age was 64 (27 – 90), 169 (45%) had de novo stage IV disease, 96% were ECOG 0-1. 284 (77%) had liver-only and 87 (23%) lung-only mets. 242 (65%) pts received p-chemo (58 pre-op alone, 134 post-op alone, 50 both). 62 (19%) pts also received a biologic agent (47/62 pre-op). Median age was 68 and 61 years in no p-chemo and p-chemo groups, respectively (p&lt;0.0001). 53% of no p-chemo pts and 23% of p-chemo pts had had prior adjuvant chemotherapy (p&lt;0.001). On MV analysis, p-chemo was a significant predictor of survival (HR 0.52, 95% CI 0.32-0.88, p=0.014). The other significant predictor of improved survival was ECOG PS of 0 (HR 0.58, p=0.019). Predictors of worse survival were rectal primary (HR 1.98 p=0.009), male gender (HR 1.69 p=0.03) and de-novo metastatic disease (HR 2.63, p=0.006). Prior adjuvant chemo, age, liver vs lung mets, use of perioperative biologics, BRAF and RAS status had no significant impact. In an exploratory analysis, the group considered “resectable” upfront (n=281) was analysed separately, perioperative chemotherapy was not a significant predictor of survival in this subgroup (HR 0.69, p=0.26). Conclusions: In routine care there is a variable approach to the use of p-chemo in pts with potentially resectable liver or lung mets. P-chemo is associated with improved survival in this analysis, although this was not confirmed in the separate analysis of the “resectable” subgroup. Due to the retrospective nature of the study confounding by unmeasurable factors is possible. This study supports ongoing consideration of P-chemo in pts with resectable mets.

657P - Patient demographics and management landscape of metastatic colorectal cancer in the third-line setting: Real-world data in an Australian population

BackgroundColorectal cancer is the third most common cancer and second leading cause of cancer mortality in Australia. In patients with metastatic disease who have progressed after two lines of therapies, survival is 4-6 months with best supportive care, and 6-8 months with newer agents. This retrospective analysis aims to explore real-world treatment landscape of metastatic colorectal cancer in the third-line setting. MethodsWe analysed the TRACC (Treatment of Recurrent and Advanced Colorectal Cancer) registry database from 2009 onwards. Patients treated with palliative intent who have progressed after two lines of therapies were included. One treatment line is defined as any combination of systemic therapy given until progression. Patient demographics, third line choices and survival outcomes were examined. ResultsA total of 2831 patients had metastatic colorectal cancer, and of these, 23% (642 patients) met study criteria. 48% (306 patients) of study population proceeded to receive third line therapy. A large proportion of patients had received doublet chemotherapy in both first and second lines. Median age was 62 years and ECOG at the start of third line was 1-2 (75%). A fluoropyrimidine-based doublet with oxaliplatin or irinotecan was the most common treatment choice in 42%. Other treatments included mono-chemotherapy +/- biological agent (23%), EGFR inhibitor alone (22%), EGFR inhibitor with doublet chemotherapy (6%), trifluridine/tipiracil (4%), regorafenib (2%), immunotherapy (<1%), clinical trials (1%), others (<1%). Median duration on third-line treatment was 2.4 months (0.07 – 40). Median overall survival (OS) was 8.7 months (0.4 – 58). ConclusionsIn a real-world Australian population, 11% of all patients diagnosed with metastatic disease received third line treatment, with commonest regimens being doublet chemotherapy. This treatment landscape may change with the approval of new drugs. Overall survival in these patients is comparable to third line trials on these agents. Analyses are underway to further characterise the breakdown of treatment regimens in all three lines in these patients, and assess survival with rechallenge regimens. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

Metastasectomy and BRAF mutation: An analysis of survival outcome in metastatic colorectal cancer.

3531 Background: Surgical resection of oligometastases improves survival in metastatic colorectal cancer (mCRC). It is unclear whether such benefit is consistently observed for BRAF V600E mutant (MT) and wild type (WT) mCRC. We conducted a retrospective analysis to explore the influence of BRAF mutation status on survival outcomes after metastasectomy. Methods: Data collected from two large prospective population databases in Australia (Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) and South Australian cancer registry). Overall survival (OS) and recurrence free survival (RFS) for BRAF MT and WT mCRC were evaluated by Kaplan-Meier method and compared by log-rank test. Results: 513 patients who had undergone metastasectomy were identified, 6% were BRAF MT. Median age 63. Metastasectomy rate was lower in BRAF MT (13 v 27%). In BRAF WT, 4% underwent resection of metastases (mets) in &gt;1 organ at diagnosis and 5% had 3 or 4 metastasectomies versus none in BRAF MT. Median OS in BRAF MT v WT: 25.7 v 48.5 months (HR 1.95; 1.18-3.22). In a multivariate model adjusting for variables which were significant on univariate analysis, OS differences were not statistically significant. Right primary tumor, intact primary, &gt;1 metastatic sites at diagnosis, non R0 resection, peritoneal mets and synchronous mets were independent predictors of worse OS. Among 364 patients with RFS data there was no difference between BRAF MT and WT (16 v 19 months, p=0.09). Rate of downsizing was higher with triplet chemo than doublet +/- bevacizumab or doublet/EGFR in BRAF WT (50 v 30%) as well as MT (33 v 11%). Conclusions: Median OS was &gt; 2 years in BRAF MT V600E after metastasectomy in this study consistent with an OS benefit. OS did not differ after metastasectomy between BRAF MT and WT in a multivariate model. Presence of BRAF MT should not impact patient selection for metastasectomy.[Table: see text]

Right versus left sided metastatic colorectal cancer: Teasing out clinicopathologic drivers of disparity in survival.

Metastatic colorectal cancer (mCRC) patients with a right-sided primary (RC) have an inferior survival to mCRC arising from a left-sided primary (LC). Previous analyses have suggested multiple factors contribute. The Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) Registry prospectively captured data on consecutive mCRC patients. RC were defined as tumors proximal to the splenic flexure; LC were those at and distal to the splenic flexure and included rectal cancers. Patient,tumor, treatment, and survival data were analyzed stratified by side. Of 2306 patients enrolled from July 2009-March 2018, 747 (32%) had an RC. Patients with RC were older, more likely to be female and have a Charlson score ≥3. RC were more frequently BRAF mutated, deficient in mismatch repair, associated with peritoneal metastases, and less likely to receive chemotherapy. Progression-free survival on first-line systemic therapy was inferior for RC patients (8.1vs. 10.8 months, hazard ratio [HR] for progression in RC 1.38, P<0.001). Median overall survival for all RC patients was inferior (19.6vs. 27.5 months, HR for death in RC 1.44, P<0.001), and inferior within the treated (21vs. 29.5 months, HR 1.52, P<0.001) and untreated subgroups (5.9vs. 10.3 months, HR 1.38, P=0.009). Primary side remained a significant factor for overall survival in multivariate analysis. Our data from a real-world population confirms the poorer prognosis associated with RC. Primary tumor location remains significantly associated with overall survival even when adjusting for multiple factors, indicating the existence of further side-based differences that are as yet undefined.

Left- versus right-side metastatic colorectal cancer: Teasing out clinicopathologic drivers of disparity in survival.

623 Background: Patients with metastatic colorectal cancer (mCRC) arising from a right sided colorectal cancer (RC) have an inferior survival versus patients with a left sided colorectal cancer (LC). Previous analyses have suggested that multiple factors contribute. Methods: The Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) Registry has prospectively captured comprehensive data on consecutive mCRC patients since 2009. For this analysis LC were defined as primary tumors at or distal to the splenic flexure and included rectal cancers. We analysed patient, tumor, treatment and outcome data. Results: Of 2306 patients enrolled from July 2009–March 2018, median age 67 years (range 18–100), 1559 (67.6%) had a LC. Patients with a RC were older (median 71 vs 65 years, p &lt; 0.001), more likely to be female (50.2% vs 36.9%, p &lt; 0.001) and to have a Charlson score ≥ 3 (67.5% vs 54.6%, p &lt; 0.001). More common in RC, where tested, were BRAF mutations (22.3% vs 7.2%, p &lt; 0.001) and deficient mismatch repair (6.4% vs 1.5%, p &lt; 0.001), but not RAS mutations. Peritoneal metastases were more frequent in RC (29.7% vs 14.9%, p &lt; 0.001). RC patients were more likely to have their primary tumor resected (77.9% vs 70.6%, p &lt; 0.001) and to receive less first-line chemotherapy (72.2% vs 78.7%, p = 0.001). Progression-free survival on first-line systemic therapy was inferior for RC patients (8.1 vs 10.8 months, HR 1.38, p &lt; 0.001). Median overall survival (OS) for all RC patients was inferior (19.6 vs 27.5 months, HR 1.44, p &lt; 0.001). Primary side remained a significant factor for OS in multivariate analysis. Conclusions: Our data confirms the poor prognosis associated with RC, contributed to by multiple factors. However, primary side remains significant even when adjusting for these, indicating the existence of further as yet undefined differences. [Table: see text]

How accurate are medical oncologists' impressions of management of metastatic colorectal cancer in Australia?

Current efforts to understand patient management in clinical practice are largely based on clinician surveys with uncertain reliability. The TRACC (Treatment of Recurrent and Advanced Colorectal Cancer) database is a multisite registry collecting comprehensive treatment and outcome data on consecutive metastatic colorectal cancer (mCRC) patients at multiple sites across Australia. This study aims to determine the accuracy of oncologists' impressions of real-word practice by comparing clinicians' estimates to data captured by TRACC. Nineteen medical oncologists from nine hospitals contributing data to TRACC completed a 34-question survey regarding their impression of the management and outcomes of mCRC at their own practice and other hospitals contributing to the database. Responses were then compared with TRACC data to determine how closely their impressions reflected actual practice. Data on 1300 patients with mCRC were available. Median clinician estimated frequency of KRAS testing within 6 months of diagnosis was 80% (range: 20-100%); the TRACC documented rate was 43%. Clinicians generally overestimated the rates of first-line treatment, particularly in patients over 75 years. Estimate for bevacizumab in first line was 60% (35-80%) versus 49% in TRACC. Estimated rate for liver resection varied substantially (5-35%), and the estimated median (27%) was inconsistent with the TRACC rate (12%). Oncologists generally felt their practice was similar to other hospitals. Oncologists' estimates of current clinical practice varied and were discordant with the TRACC database, often with a tendency to overestimate interventions. Clinician surveys alone do not reliably capture contemporary clinical practices in mCRC.

Examining progression-free survival in first- and second-line treatment for BRAF-mutant metastatic colorectal cancer (CRC).

728 Background: BRAF mutated (BRAFm) CRC represents ~10% of all CRC and is associated with significantly poorer prognosis. However, responses to chemotherapy do still occur. Some data suggest that the poor prognosis associated with BRAFm CRC is dominated by substantially poorer second line PFS (PFS2), whereas first line PFS (PFS1) was similar for both BRAFm and BRAF wildtype (BRAFwt) CRC. Using a large multicenter dataset, our study aimed to examine PFS1 and PFS2 in BRAFm versus BRAFwt CRC. Methods: Prospectively collected data from the Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) database was interrogated. PFS was calculated and compared in patients with BRAFm versus BRAFwt CRC. Median survival was determined by the Kaplan-Meier method and compared using the log rank test. Results: TRACC identified 523 CRC patients with known BRAF mutation status, who received first-line chemotherapy: 53 (10%) were BRAFm, while 470 (90%) were BRAFwt. At the time of data analysis, only 231 (44%) CRC patients had received second-line chemotherapy, of which 21 (9%) were BRAFm and 210 (91%) were BRAFwt. PFS1 analyses demonstrated significantly poorer survival in the BRAFm population (Median 7.8mo versus 11.5mo, HR 1.72, p = 0.0026). PFS2 analyses revealed similar findings for the BRAFm population, albeit non-significant due to smaller numbers (Median 5.5mo versus 7.7mo, HR1.26, p = 0.44). Conclusions: Our study demonstrated that BRAFm CRC was associated with poorer PFS in both first- and second-line settings. Additional analyses will be performed to examine the impact of different treatment strategies and other clinicopathological features.

Left versus right sided colorectal cancer: Teasing out drivers of disparity in outcomes in metastatic disease.

682 Background: Patients (pts) with metastatic colorectal cancer (mCRC) arising from a right sided colon cancer (RCC) have an inferior survival versus pts with a left sided primary (LCC). Previous analyses have suggested that multiple factors contribute. Methods: The Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) Registry has prospectively collected data on consecutive mCRC pts at 32 sites (Australia and Hong Kong) from July 2009. LLC were defined as those distal to the splenic flexure. We analysed patient, tumour, treatment and outcome data. Results: Of 1763 patients, median age 67 years (range 18 – 100), 1201 patients (68.1%) had a LCC. RCC were more common in pts ≥ 70 years old (53.9% vs 38.5%, p &lt; 0.01) and females (50.7%, p &lt; 0.01). Where tested, KRAS (50.9% vs 41.5%, p &lt; 0.01) and BRAF (19.1% vs 6.4%, p &lt; 0.01) mutations were more common in RCC. Where tested, dMMR was more common in RCC (11.0% vs 3.2%, p &lt; 0.01). Pts with a RCC more often had peritoneal metastases (25.9% vs 12.5%%, p &lt; 0.01) and were less likely to have liver metastases (69.8% vs 77.9%, p &lt; 0.01) or resection of metachronous metastases (31.8% vs 43.6%, p &lt; 0.01). LCC more commonly received chemotherapy in the 1st (86.1% vs 80.3%, p = 0.02) and 2nd (49.7% vs 43.0%, p = 0.04) line setting. There was no difference in ECOG performance status or co-morbidity for LCC vs RCC. Overall survival for pts with a RCC was 20.6 months vs 27.9 months for LCC L-sided tumours (HR 1.395, p &lt; 0. 0001). Conclusions: Our data confirms that pts with mCRC arising from a RCC have an inferior survival. This appears multifactorial due to associations with adverse clinical and molecular features, metastatic pattern, and less therapy, some of which are related. A multivariate analysis is being performed.

Patterns of care and outcomes for elderly patients with metastatic colorectal cancer in Australia.

The elderly accounts for a large proportion of patients with metastatic colorectal cancer (mCRC). This study reviews patterns of care and outcomes for elderly patients with mCRC in the community setting. Elderly patients (≥ 65 years) with mCRC on the TRACC (Treatment of Recurrent and Advanced Colorectal Cancer) registry were identified. Treatment, bevacizumab-related adverse events, and overall survival (OS) were analysed by age cohorts, comparing those aged 65-74 vs. 75-84 vs. ≥ 85 years and correlated with potential prognostic factors. Factors affecting chemotherapy and bevacizumab administration were analysed using logistic regression analysis. Of 1439 patients, 363, 352, and 106 were aged 65-74, 75-84, and ≥ 85 years, respectively. 584 (71%) patients received first-line chemotherapy, with chemotherapy use declining with advancing age (84%, 69%, and 34% in 65-74-, 75-84- and ≥ 85-year-olds, respectively). Seven (10%) patients aged ≥ 85 years were not treated with chemotherapy on the basis of age alone. Only 10 of 36 very elderly patients who received chemotherapy also received bevacizumab. Factors affecting bevacizumab administration included age, treatment location, and comorbidities. There was no impact of age on bevacizumab-related adverse events. Resection of metastatic disease occurred in 173 (21%) patients overall, with rates declining with age (26% vs. 21% vs. 6%). Chemotherapy usage and resection of metastatic disease decline with advancing age. A minority of patients are not treated with systemic therapy due to advanced age alone. Our cohort suggests underutilisation of bevacizumab in older patients, but where given, toxicity rates did not increase with age.

Novel quality indicators for metastatic colorectal cancer management identify significant variations in these measures across treatment centers in Australia.

Defining multidisciplinary quality of care indicators (QCIs) for metastatic colorectal cancer (mCRC) could improve understanding of variations in routine practice care. This may identify areas of below-average performance, which could then be addressed by clinicians to improve the quality of care delivered. This study aimed to define a panel of QCIs in mCRC and, based on these QCIs, to evaluate quality of care across multiple Australian sites. A panel of clinicians with expertise in colorectal cancer defined evidence-based or best practice-based QCIs relevant to the routine multidisciplinary management of mCRC patients through structured consensus discussion. Related data were extracted from the Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) registry, a prospectively maintained database recording comprehensive details on consecutive mCRC patients across multiple Australian hospitals. Variations in QCIs across sites were explored. Of 13 QCIs defined, data related to 10 were reliably extracted from TRACC. Analysis of data on 1276 patients across 10 sites demonstrated low rates of screening for hereditary nonpolyposis colorectal cancer in young patients and significant variation in surveillance-detected recurrences, lung resection rates and palliative chemotherapy use. Exploratory analyses suggested correlation between liver resection rates and survival. We have defined a novel set of mCRC QCIs and have demonstrated wide variation in the quality of care of mCRC across multiple Australian sites. With further validation to confirm a direct correlation between QCI and patient outcomes, these QCIs could be applied to improve the quality of care received by all mCRC patients.

Gastrointestinal perforation in metastatic colorectal cancer patients with peritoneal metastases receiving bevacizumab.

To investigate the safety and efficacy of adding bevacizumab to first-line chemotherapy in metastatic colorectal cancer patients with peritoneal disease. We compared rates of gastrointestinal perforation in patients with metastatic colorectal cancer and peritoneal disease receiving first-line chemotherapy with and without bevacizumab in three distinct cohorts: (1) the AGITG MAX trial (Phase III randomised clinical trial comparing capecitabine vs capecitabine and bevacizumab vs capecitabine, bevacizumab and mitomycinC); (2) the prospective Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) registry (any first-line regimen ± bevacizumab); and (3) two cancer centres in New South Wales, Australia [Macarthur Cancer Therapy Centre and Liverpool Cancer Therapy Centre (NSWCC) from January 2005 to Decenber 2012, (any first-line regimen ± bevacizumab). For the AGITG MAX trial capecitabine was compared to the other two arms (capecitabine/bevacizumab and capecitabine/bevacizumab/mitomycinC). In the AGITG MAX trial and the TRACC registry rates of gastrointestinal perforation were also collected in patients who did not have peritoneal metastases. Secondary endpoints included progression-free survival, chemotherapy duration, and overall survival. Time-to-event outcomes were estimated using the Kaplan-Meier method and compared using the log-rank test. Eighty-four MAX, 179 TRACC and 69 NSWCC patients had peritoneal disease. There were no gastrointestinal perforations recorded in either the MAX subgroup or the NSWCC cohorts. Of the patients without peritoneal disease in the MAX trial, 4/300 (1.3%) in the bevacizumab arms had gastrointestinal perforations compared to 1/123 (0.8%) in the capecitabine alone arm. In the TRACC registry 3/126 (2.4%) patients who had received bevacizumab had a gastrointestinal perforation compared to 1/53 (1.9%) in the chemotherapy alone arm. In a further analysis of patients without peritoneal metastases in the TRACC registry, the rate of gastrointestinal perforations was 9/369 (2.4%) in the chemotherapy/bevacizumab group and 5/177 (2.8%) in the chemotherapy alone group. The addition of bevacizumab to chemotherapy was associated with improved progression-free survival in all three cohorts: MAX 6.9 m vs 4.9 m, HR = 0.64 (95%CI: 0.42-1.02); P = 0.063; TRACC 9.1 m vs 5.5 m, HR = 0.61 (95%CI: 0.37-0.86); P = 0.009; NSWCC 8.7 m vs 6.8 m, HR = 0.75 (95%CI: 0.43-1.32); P = 0.32. Chemotherapy duration was similar across the groups. Patients with peritoneal disease do not appear to have an increased risk of gastrointestinal perforations when receiving first-line therapy with bevacizumab compared to systemic therapy alone.

P0183 Resection of colorectal cancer metastases in routine practice

Background The optimal management of metastatic colorectal cancer (mCRC) involves a multimodality approach. Complete resection of limited metastatic disease is a critical, potentially curative, intervention for a minority of patients. Data for resection rates and outcomes in routine clinical practice are limited. Methods We analysed records of patients enroled in the Australian prospective mCRC registry TRACC (Treatment of Recurrent and Advanced Colorectal Cancer). Data collection commenced in July 2009, with 14 sites now contributing. Treatment intent was recorded at initial patient review as curative, potentially curative, or palliative. Findings Of 1012 patients, 213 (21%) underwent metastasectomy, 179 (84%) with R0 resections. Liver (55.4%) and lung (20.2%) were the most commonly resected disease sites. For 26 (12.2%) patients, the initial treatment intent had been palliative. Patients who had metastases resected were younger (median age 63 years versus 70 years, p p p p p p = 0.046) and a single disease site (61.3% versus 54.5%; p = 0.029) than had patients in public hospitals, but the median age of private patients was older (70 years versus 67 years; p = 0.041). Overall survival for resected patients was equivalent in both groups (median undefined, hazard ratio 0.96, 95% confidence interval 0.45–2.06; p = 0.919). Interpretation In routine practice, a substantial proportion of patients with mCRC undergo resection of distant metastases, including some patients initially considered incurable. Significant variation between sites has been noted, which might relate to differences in patient population or a more aggressive treatment approach. Multivariate analyses and review of individual centre data are planned to explore reasons for potential underuse of this critical intervention.