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Background Colorectal cancer is the third most common cancer and second leading cause of cancer mortality in Australia, thus carrying a significant disease burden. Aims This analysis aims to explore real-world treatment landscape of metastatic colorectal cancer in the third-line setting. Methods 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. Results 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). Conclusions 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.

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 =

e16072 Background: The KRASG12C mutation is present in 3% of colorectal cancer and is of particular interest given the recent development of specific targeting drugs. Previous data suggest KRAS (all) mutations may impact prognosis. Here we assess the clinical features and outcomes of real world patients with KRASG12C mutant metastatic colorectal cancer (mCRC) to explore any clinicopathologic associations and prognostic impact. Methods: Patients diagnosed with mCRC between January 2011 and December 2018 were included in this prospective mCRC registry. Patients with BRAF mutations, unknown or unspecified KRAS variants were excluded. Clinicopathologic features, treatment and overall survival (OS) were compared for RAS wildtype (RASWT) and KRASG12C mutant patients, and between KRASG12C and other (RASother) mutations. Results: Of 1308 patients analysed, 674 (52%) were RASmut, of whom 56 (8.3%) were KRASG12C. More patients with KRASG12C were female compared to RASother and RASWT (Table). No differences were observed in primary tumor location, number of metastatic sites and distribution of metastases. The proportion of patients undergoing metastasectomy was similar between KRASG12C and RASother, and KRASG12C and RASWT. There was no difference in the proportion of patients receiving systemic therapy. RASWT patients received more lines of therapy. Median OS was similar between KRASG12C, RASother, and RASWT: 31.7 vs 29.2 vs 31.8 months respectively (P = 0.545). Conclusions: KRASG12C mutations were observed in 4.3% of mCRC patients and in 8.3% of RAS mutant cases. Patients with KRASG12C have comparable clinical features to RASWT or RASother mCRC. Treatment and survival were also similar between groups. KRASG12C does not appear to be prognostic, but may be an important predictive biomarker as promising targeted therapies continue to be developed. [Table: see text]

Background Emerging evidence on the optimal use of chemotherapy and biologics in patients with metastatic colorectal cancer should impact management in routine care. Recent studies have demonstrated benefits for initial triplet chemotherapy (5-fluorouracil, oxaliplatin and irinotecan, FOLFOXIRI) and for initial treatment with an epidermal growth factor receptor inhibitor (EGFRi) in patients with a RAS wild-type tumour and a left-sided primary tumour. Aim To explore evolving pattern of metastatic colorectal cancer care over time in Australia. Methods We analysed data from the Treatment of Recurrent and Advanced Colorectal Cancer registry. Results From July 2009 to December 2017, 2552 metastatic colorectal cancer patients were entered into the Treatment of Recurrent and Advanced Colorectal Cancer registry. Of 1585 patients who initially underwent chemotherapy, treatment was with a doublet in 76%. FOLFOXIRI was given to 22 patients (1.4%), mostly young patients and those with potentially resectable disease. Along with first-line chemotherapy, 61% received bevacizumab, while 3.3% received an EGFRi, predominantly over the last 2 years. Within the KRAS wild-type left-sided tumour cohort, EGFRi use increased from 9% in 2015 to 37% in 2017. Across treatment sites, there was a wide variation in the utilisation of FOLFOXIRI and EGFRi therapy; bevacizumab use was more consistent. A clear impact on survival outcomes from these regimens is not evident, potentially due to multiple confounders. Conclusion Doublet chemotherapy + bevacizumab remains the dominant initial strategy, with limited uptake of triplet chemotherapy and of EGFRi. Potential explanations include uncertainty about the significance of post hoc analyses for EGFRi and concerns regarding adverse events for both strategies.

Background The FIRE-3 [5-fluorouracil, folinic acid, and irinotecan (FOLFIRI) plus cetuximab versus FOLFIRI plus bevacizumab in first line treatment colorectal cancer (CRC)] study reported that first-line FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab resulted in similar progression-free survival (PFS) but improved overall survival (OS). A potential explanation is that the initial biologic agent administered in metastatic CRC (mCRC) affects later line efficacy of the other treatments. We sought to test this hypothesis. Materials and Methods We interrogated our mCRC registry (Treatment of Recurrent and Advanced Colorectal Cancer) regarding treatment and outcome data for RAS wild-type patients receiving epidermal growth factor receptor inhibitors (EGFRIs) in second and subsequent lines. Survival outcomes from the beginning of EGFRI use were determined as a function of previous bevacizumab use and the interval between ceasing bevacizumab and beginning EGFRI use. Results Of 2061 patients, 222 eligible patients were identified, of whom 170 (77%) had received previous bevacizumab and 52 (23%) had not. PFS and OS from the start of EGFRIs did not differ by previous bevacizumab use (3.8 vs. 4.2 months; hazard ratio [HR], 1.12; P = .81; 9.0 vs. 9.2 months; HR, 1.19; P = .48, respectively) for the whole cohort or when analyzed by the primary tumor side (HR for left side, 1.07; P = .57; HR for right side, 1.2; P = .52). PFS was significantly shorter with right-sided primary tumors when the interval between bevacizumab and EGFRI use was 6 months (median, 2.2 vs. 6 months; HR, 2.23; P = .01) but not with left-sided tumors (median, 4.2 vs. 5.5 months; HR, 1.12; P = .26). Conclusion Previous bevacizumab use had no effect on the activity of subsequent EGFRIs. The apparent effect of time between biologic agents in right-sided tumors might reflect patient selection.

Aim The potential beneficial interaction between erlotinib and chemotherapy may require sequencing or pharmacodynamic separation. The aim of this study was to evaluate the efficacy and tolerance of sequential erlotinib and gemcitabine versus gemcitabine monotherapy as first-line therapy in elderly or ECOG PS-2 patients with advanced non-small cell lung carcinoma. Methods The primary objective of this multicenter randomized Phase II study was progression-free survival (PFS). Secondary objectives were overall response rate (ORR), disease control rate, response duration, overall survival and safety. Patients were randomized to either gemcitabine (1250 mg/m2 Day 1, 8 q28 days) followed by erlotinib (150 mg/day on day 15 through day 28), (EG-arm), or gemcitabine monotherapy (1000 mg/m2 Days 1, 8, 15 q28 days), (G-arm) for up to six cycles. Results Fifty-four patients were recruited, 28 G-arm and 26 EG-arm. Overall, efficacy results were not significantly different between study arms. Median PFS and ORR for the G- versus EG-arms were 8.0 versus 10.3 weeks (hazard ratio 1.3; 95% confidence interval [0.63;2.68]; P = 0.48) and 7.1 versus 3.8 percent respectively (difference −3.30; 95% confidence interval [−17.5;10.9]). The majority of adverse events (AEs) in both arms were Grade 1–2. The commonest AEs recorded in the EG- and G-arms were rash-like events (65 percent) and nausea (42 percent) respectively. Four patients (17 percent) in EG-arm and five (16 percent) in G-arm experienced at least one treatment-related serious AE. Conclusions In this study, patients with non-small cell lung carcinoma at ECOG PS-2 or aged ≥70 years derived no efficacy advantage from sequential erlotinib in combination with gemcitabine relative to gemcitabine alone. No unexpected safety findings were noted.

Background Colorectal 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. Methods We 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. Results A 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 ( Conclusions In 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 study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

Concurrent chemoradiotherapy (CCRT) has become the standard of care for patients with unresectable stage III non-small cell lung cancer (NSCLC). The comparative merits of two widely used regimens: carboplatin/paclitaxel (PC) and cisplatin/etoposide (PE), each with concurrent radiotherapy, remain largely undefined. Records for consecutive patients with stage III NSCLC treated with PC or PE and ≥60 Gy chest radiotherapy between 2000 and 2011 were reviewed for outcomes and toxicity. Survival was estimated using the Kaplan-Meier method and Cox modeling with the Wald test. Comparison across groups was done using the student's t and chi-squared tests. Seventy-five (PC: 44, PE: 31) patients were analyzed. PC patients were older (median 71 vs. 63 years; P = 0.0006). Other characteristics were comparable between groups. With PE, there was significantly increased grade ≥3 neutropenia (39% vs. 14%, P = 0.024) and thrombocytopenia (10% vs. 0%, P = 0.039). Radiation pneumonitis was more common with PC (66% vs. 38%, P = 0.033). Five treatment-related deaths occurred (PC: 3 vs. PE: 2, P = 1.000). With a median follow-up of 51.6 months, there were no significant differences in relapse-free survival (median PC 12.0 vs. PE 11.5 months, P = 0.700) or overall survival (median PC 20.7 vs. PE 13.7 months; P = 0.989). In multivariate analyses, no factors predicted for improved survival for either regimen. PC was more likely to be used in elderly patients. Despite this, PC resulted in significantly less hematological toxicity but achieved similar survival outcomes as PE. PC is an acceptable CCRT regimen, especially in older patients with multiple comorbidities.

With an ever-increasing focus on personalized medicine, all factors known to affect treatment response need to be considered when defining optimal therapy for individual patients. While the prognostic impact of primary tumor site on colorectal cancer (CRC) outcomes is established, emerging data suggest potential differences in response to biologic therapies. We studied the impact of tumor site on bevacizumab efficacy in patients with metastatic CRC.We analyzed data of patients in an Australian prospective multicenter metastatic CRC (mCRC) registry who received first-line chemotherapy. Tumor site was defined as right colon, cecum to transverse; left colon, splenic flexure to rectosigmoid; and rectum. Kaplan-Meier and Cox models were used for survival analyses.Of 926 patients, 297 had right colon, 354 left colon, and 275 rectum primary disease. Median age was 68.6, 65.9, and 63.3 years, respectively (P = .001). Right colon disease was significantly associated with intraperitoneal spread (P .0001), while left colon and rectum disease preferentially metastasized to the liver and lungs, respectively (P .0001 in both settings). A total of 636 patients (68.7%) received bevacizumab. Progression-free survival was superior for bevacizumab-treated patients in all groups but appeared greatest in right colon disease (hazard ratio, 0.46; 95% confidence interval, 0.36-0.60; P ≤ .001). Overall survival was longest in patients with disease of the rectum, followed by left colon and right colon (median, 26.2, 23.6, and 18.2 months, respectively; P = .0004).Tumor site appears to be prognostic in mCRC, with rectum and right colon disease associated with the best and worst outcomes, respectively. Patients who received bevacizumab in addition to chemotherapy had superior outcomes, with the effect appearing greatest in patients with right colon disease.

8514 Background: Early phase trials of anti-programmed death 1 (PD-1) antibodies have demonstrated important responses in malignant mesothelioma (MM). Expression of the ligand, PD-L1, is a potential biomarker for PD-1 directed therapy use and is expressed in a significant proportion of MM. We present results for a cohort treated with PD-1 inhibitory antibodies and assessed for PD-L1 expression. Methods: Patients (pts) with unresectable pleural or peritoneal mm treated with anti-PD-1 antibodies were included. Data was collected retrospectively. Radiological response was assessed using RECIST 1.1. Overall survival (OS) and progression-free survival (PFS) were evaluated. PD-L1 expression was assessed with IHC clone E1L3N (Cell Signaling Technology). PD-L1 positivity was defined as membranous expression on tumour cells: > 5% for PD-L1+ and > 50% for PD-L1hi. Results: Forty-six pts were treated between July 2015 and January 2017. Median age was 66.5 years, ECOG PS was 0/1 in 3/46 (7%) and 35/46 (76%) respectively. Most were male (83%), and 43/46 (93%) had ≥1 prior therapy, with a median of 2 (range 0 - 5). The predominant histology was epithelioid (n = 32/46; 70%). Pembrolizumab was used in 45/46 and BGB-A317 (a PD-L1 antibody) in 1 pt. Of the 46 pts, the overall response rate (ORR) was 15% (7 PR) with 15/46 (33%) achieving stable disease, giving a DCR of 44%. Progression was seen in 24/46 (52%). Median OS for the entire cohort was 8.0 months (95% CI: 2.3 – 11.9). Median duration of response was not yet reached (range 1.5 -19.8). PD-L1 testing was performed in 14 samples, with PD-L1+ in 5 (36%) and PD-L1hi in 4 (29%). The ORR was 40% (2 PR, 3 SD) with PD-L1+, 50% (2 PR, 2 SD) with PD-L1hi and 22% (2/9 patients) with negative expression. PFS and OS were greater with both PD-L1+ (PFS HR: 0.26, 95% CI 0.05 – 1.32, p = 0.10) and PD-L1hi(PFS HR: 0.17, 95% CI 0.02 – 1.47, p = 0.11). PD-L1+ positivity remained a borderline predictor of improved survival on multivariate analysis (p = 0.06). Complete PD-L1 analysis will be presented at the meeting. Conclusions: PD-1 targeted therapy demonstrated a clinically significant response rate in this cohort of mm patients. Initial analysis suggests PD-L1 expression is correlated with improved response and survival.

785 Background: Resection of metastases with curative intent is an integral component of mCRC management. However, relapse rates are high and identifying patients most likely to benefit from this approach is of considerable importance. Among patients with mCRC, mutations (mt) in RAS and BRAF genes portent a worse prognosis. Our hypothesis, therefore, is that patients harbouring these mutations may have a higher relapse rate after resection of metastases. We also wished to analyse clinical predictors of relapse, including site of metastases. Methods: We interrogated the TRACC database of patients undergoing resection with curative intent who had mutation status available. The frequency of RAS and BRAF mt was established and their association with clinical parameters determined. Relapse free (RFS) and overall survival (OS), from the date of resection, was estimated for the mt and wild type (wt) groups using the Kaplan Meier method. Multivariate analysis is planned to investigate factors associated with RFS, including stage of the primary tumour, synchronous metastases, site and number of metastases, CEA, peri-operative chemotherapy use, site of the primary (left v right) and RAS and BRAF mutation status. Results: 188 patients were identified. 89 were KRAS/BRAF wt, 92 KRAS mt and 7 BRAF mt. 40% had presented with metastatic disease and 27% had a right sided primary. 76%, 22% and 2% underwent resection of liver, lung or both metastases. Microscopic resection margin was involved in 6%. Resection was performed prior to any chemotherapy in 48%. No difference was seen in relapse free or overall survival between the mt and wt groups. Conclusions: We found no difference in relapse free or overall survival by mutation subgroup suggesting this should not influence suitability for curative intent resection, but analyses is planned on a much larger cohort once data is available. A multivariate analysis, adjusting for important prognostic variables, is planned.

The results of a questionnaire answered by 205 medical patients are reported (100 patients with cancer and 105 with other medical conditions). The questionnaire examined beliefs and preferences regarding various aspects of cancer, including expectations of medical management and treatment. The issues examined relate to beliefs and preferences about information giving, trust of doctors' control of decision making, expectations of help, expectations of treatment, the treatment of cancer pain including morphine use, and issues of terminal care. Some patients appear to hold the inconsistent beliefs that doctors should tell them all they want to know, but that doctors do not know a lot of what they would like to be told. They were also ambivalent about who should make decisions, patient or doctor, suggesting a preference for collaborative consensus decision making. It may be important to inform patients more clearly about what doctors can and cannot reasonably be expected to know and do. Some incorrect beliefs about management were related to fear about having cancer. The results suggest the need for better communication between patients and their professional carers and the need for accessible health information about cancer management to be available to the general public.

PURPOSE To compare the efficacy and toxicity profiles of a combination of fluorouracil (5-FU) with recombinant human interferon alfa-2a (Roferon-A; Hoffman La-Roche AG, Basel, Switzerland) versus the combination of 5-FU with leucovorin (LV) in the treatment of advanced colorectal cancer. PATIENTS AND METHODS A total of 496 previously untreated colorectal cancer patients were randomized to receive either Roferon-A (9 MIU) subcutaneously three times per week, with 5-FU (750 mg/m2/d) by continuous intravenous (i.v.) infusion (CIV) on days 1 to 5, then, after a 9-day hiatus, as a weekly i.v. bolus at the same dose (IFN/5-FU); or LV (200 mg/m2/d) by i.v. infusion plus 5-FU (370 mg/m2/d) by i.v. bolus on days 1 to 5, repeated every 4 weeks (LV/5-FU). RESULTS There were no significant differences between IFN/5-FU and LV/5-FU in the overall response rate (21% v 18%), duration of response (7.3 v 6.2 months), or survival time (median, 11.0 v 11.3 months). Toxicity profiles differed; constitutional symptoms and myelosuppression were more frequent and more severe with IFN/5-FU, and gastrointestinal symptoms with LV/5-FU. More patients interrupted treatment for adverse events (AEs) with IFN/5-FU than with LV/5-FU. Five treatment-related deaths occurred with each regimen. CONCLUSION The combination IFN/5-FU produced response rates, response durations, and survival times similar to those with LV/5-FU. Biochemical modulation of 5-FU by either IFN or LV appears to result in equivalent efficacy; however, fewer patients were able to tolerate the specified IFN/5-FU combination used in this study.

For a number of cytotoxics, a relationship between efficacy and plasma concentrations has recently been demonstrated. Lean body mass has been demonstrated to be a useful parameter for predicting drug clearance for a number of non-cytotoxic drugs. However, the role of lean body mass in predicting drug clearance for any cytotoxic drug has not been previously reported. Our purpose was to investigate lean body mass as a predictor of epirubicin clearance. Pharmacokinetic studies were performed in 10 patients receiving single agent epirubicin. Although preliminary, this study suggests that lean body should be further evaluated and tested in dose optimization studies.

A phase I/II study of the intralesional administration of ricin-labelled monoclonal antibodies was conducted in patients with hepatic metastases of gastrointestinal origin. The anti-carcinoembryonic antigen (CEA) antibody I-1 was conjugated to blocked ricin via a disulphide bridge. After a test dose of antibody, patients were injected with ricin-antibody conjugates under computed tomography (CT) guidance on two occasions 1 week apart. Patients with stable or responding disease would receive a third course. The dose of ricin relative to surface area was increased in a predefined manner in cohorts of 3 patients. A total of 27 patients with hepatic metastases were entered into this study. All patients had metastatic colorectal cancer (26 patients) or adenocarcinoma of unknown primary with elevated CEA levels (1 patient). The presence of malignancy was documented cytologically in 9 of 11 patients tested. Minor responses were seen in 7 patients. However, no major objective responses or changes in the growth rate of injected lesions were observed. Toxicity was generally mild, the most common being hepatic capsular pain 24-48 h after each injection. 6 patients experienced rigors. One patient had anaphylaxis. Human anti-mouse and anti-ricin antibody responses were observed. Although substantial amounts of ricin conjugated to monoclonal antibodies were delivered into single lesions, this therapeutic approach was unsuccessful. Future studies of ricin-labelled antibodies should incorporate the systemic administration of immunoconjugates.

e14637 Background: There is a growing body of epidemiological evidence that T2DM is associated with increased incidence of, and poorer survival in CRC, while metformin use in CRC pts with T2DM has ...

Aim: With an ever-increasing focus on personalised medicine, all factors known to affect treatment response need to be considered when defining optimal therapy for individual patients (pts). While the prognostic impact of primary tumour site on CRC outcomes is established, emerging data suggest potential differences in response to biologic therapies. Here we explore the impact of tumour site on bevacizumab (BEV) efficacy in pts with mCRC. Methods: Analysis of pts in an Australian prospective multicentre mCRC registry who received first-line palliative chemotherapy from July 2009 to March 2014. Tumour site was defined as: right colon (RCC)–caecum to transverse, left colon (LCC)–splenic flexure to rectosigmoid, and rectum (RC). Kaplan-Meier and Cox models were used for survival analyses. Results: Of 698 pts, 224 had RCC, 266 LCC and 208 RC primaries. Median age was 69, 66 and 63 years respectively (p Median PFS (months) Bevacizumab vs no bevacizumab Hazard ratio * 95% CI P value RCC 8.7 vs 5.6 0.60 0.42-0.85 0.004 LCC 11.8 vs 8.3 0.69 0.49-0.96 0.028 RC 13.5 vs 9.1 0.74 0.51-1.06 0.101 * Adjusted for age, sex, PS, comorbidity. Conclusions: Tumour site was prognostic in this cohort, with RC and RCC associated with best and worst outcomes respectively. Patients who received bevacizumab in addition to chemotherapy had superior PFS, with the effect appearing greatest in RCC patients. Although known prognostic factors were adjusted for, other clinicopathologic differences that may contribute to patient outcomes cannot be excluded. Patient accrual is ongoing and molecular analyses are planned. Disclosure: H. Wong, A.J. Lomax, M. Tacey, J. Shapiro, A. Zimet, D. Yip, R. Jennens, G. Richardson, J. Tie, S. Kosmider P. Parente, L. Lim, P. Cooray, B. Tran, J. Desai and B. Wong: Roche Products Pty Ltd (Australia) has provided financial assistance for the development, installation and maintenance of this clinical database. K. Field and L. Nott declare: Roche Products Pty Ltd (Australia) has provided financial assistance for the development, installation and maintenance of this clinical database. I have also received honoraria and other renumeration from Roche. J. McKendrick: Roche Products Pty Ltd (Australia) has provided financial assistance for the development, installation and maintenance of this clinical database. I also have an advisory relationship with Roche. P. Gibbs: Roche Products Pty Ltd (Australia) has provided financial assistance for the development, installation and maintenance of this clinical database. I have also received honoraria from Roche.

e17637 Background: The ever-increasing focus on the quality of cancer care delivery is driving multiple initiatives to collect and analyse data related to quality indicators, with a major focus on ...

e14518 Background: Variation in outcomes for rectal (RC) and colon (CC) cancer have been reported, particularly in the advanced disease setting. Established differences in patterns of metastatic sp...

e14558 Background: With an ever-increasing focus on personalized medicine, all factors known to affect treatment response need to be considered when defining optimal therapy for an individual patient (pt). While the prognostic impact of primary tumor site on CRC outcomes is established, emerging data suggest potential differences in response to biologic therapies. Here we explore the impact of tumor site on BEV efficacy in pts with mCRC. Methods: Analysis of pts enrolled in an Australian prospective multicenter mCRC registry. Pts diagnosed from July 2009 to December 2013 and treated with first line chemotherapy were included. Tumor site was defined as: right colon (RCC) – cecum to transverse, left colon (LCC) – splenic flexure to rectosigmoid, and rectum (RC). Kaplan Meier and Cox models were used for survival analyses. Results: Of 541 pts, 160 (29.6%) had RCC, 201 (37.2%) LCC and 180 (33.3%) RC primaries. Median age was 69, 66 and 63 years respectively (p=0.002). There was no significant difference in pe...

PURPOSE To determine the maximum-tolerated doses (MTDs), principal toxicities, and pharmacokinetics of the combination of docetaxel and cisplatin administered every 3 weeks to patients with advanced non-small-cell lung cancer (NSCLC) who have not received prior chemotherapy and to recommend a dose for phase II studies. PATIENTS AND METHODS Patients with advanced NSCLC and performance status 0 to 2 who had not received prior chemotherapy received docetaxel over 1 hour followed by cisplatin over 1 hour with hydration. Dose levels studied were (docetaxel/cisplatin) 50/75, 75/75, 75/100, and 100/75 mg/m2 repeated every 3 weeks. Colony-stimulating factor (CSF) support was not used. Pharmacokinetics of docetaxel and cisplatin were studied in the first cycle of therapy. Most patients (79%) had metastatic disease or intrathoracic recurrence after prior radiation and/or surgery. RESULTS Of 24 patients entered, all were assessable for toxicity and 18 for response. The MTD schedules were docetaxel 75 mg/m2 with cisplatin 100 mg/m2 (dose-limiting toxicities [DLTs] in five of six patients), and docetaxel 100 mg/m2 with cisplatin 75 mg/m2 (DLTs in two of two patients, including one fatal toxicity). Limiting toxicities were febrile neutropenia and nonhematologic, principally diarrhea and renal. Two patients had neutropenic enterocolitis. Pharmacokinetics of both drugs were consistent with results from single-agent studies, which suggests no major pharmacokinetic interaction. Neutropenia was related to docetaxel area under the plasma concentration-versus-time curve (AUC). An alternative schedule was investigated, with cisplatin being administered over 3 hours commencing 3 hours after docetaxel, but toxicity did not appear to be less. Independently reviewed responses occurred in eight of 18 patients (44%; 95% confidence interval, 22% to 69%), most following 75 mg/m2 of both drugs. CONCLUSION Docetaxel 75 mg/m2 over 1 hour followed by cisplatin 75 mg/m2 over 1 hour is recommended for phase II studies. The responses seen in this phase I study suggest a high degree of activity of this combination in previously untreated advanced NSCLC.

e18559 Background: Concurrent chemoradiotherapy (CCRT) has become the standard of care for patients (pts) with unresectable stage III NSCLC. Although 60Gy of radiotherapy is accepted as the standard radiation dose, the concurrent chemotherapy regimen is idiosyncratic to the institution with PC generally reserved for older and less fit pts. We retrospectively reviewed outcomes and toxicity of two widely used regimens at our institution (Austin Health, Melbourne): weekly PC (Belani et al, 2005) versus (vs) PE given weeks 1 and 5 (SWOG 9019) each with concurrent chest radiotherapy. Methods: Charts from stage III NSCLC pts treated with radical dose CCRT between 2000-2011 were reviewed. Clinical data including demographics, toxicity, and response were reviewed. Results: A total of 83 (PC: 50, PE: 33) pts were treated. PC pts were older [median age (range) 70 year (44-83) vs 63 year (32-76); p=0.001]. Other characteristics were comparable in PC and PE groups (Table). Increased grade (gr) ≥3 neutropenia was seen with PE (39% vs 12%, p=0.008). Other gr ≥3 toxicities were similar including febrile neutropenia, esophagitis and pneumonitis. With a median follow up of 17.2 months (mo), no statistical difference in overall survival (OS) (median PC 21.3 mo vs PE 13.7 mo; p=0.690) and relapse free survival (median PC 12.0 mo vs PE 11.1 mo; p=0.934) were observed. In multivariate analysis, where treatment type and age were included in the model, only more advanced stage predicted poorer OS (p=0.045). Conclusions: PC was more likely to be used in elderly pts. Despite this, PC resulted in significantly less hematological toxicity but achieved similar survival outcomes compared to PE. PC is an acceptable CCRT regimen especially in older pts. [Table: see text]

497 Background: Potential differences between public and private cancer care in Australia include the degree of subspecialisation, multidisciplinary clinic review, access to clinical trials and continuity of care, all of which could impact treatment and outcomes. Here we compared demographics, tumour details, treatment and survival outcomes for patients (pts) with newly diagnosed metastatic colorectal cancer (mCRC) treated in the public versus private setting. Methods: This research was conducted using the TRACC (Treatment of Recurrent and Advanced Colorectal Cancer) mCRC clinical research database. Data collection began in June 2009 and is ongoing at 15 Australian centres. Here, data from four public and eight private hospitals are presented. Results: Of 671 pts, 253 (38%) were treated at public hospitals and 418 (62%) at private centres. For public versus private pts there was no significant difference in median age or percentage with good performance status. More private pts received first-line chemotherapy (89% vs 80%, p=0.002), but there were no significant difference in the use of bevacizumab (50% versus 43%, p=0.10). Similar proportions received combination therapy (72% private vs 68% public) but the use of single agent oral capecitabine was higher for private patients (9% vs 4%, p=0.03). More public pts were enrolled in a first-line clinical trial (17.3% vs 1.2%, p

Docetaxel (Taxotere ® ; T), a semi-synthetic taxoid has considerable single agent activity in NSCLC with a response rate of 38% (Francis et al. , JCO12; 1232, 1994). We recently reported the results of a phase I trial of T in combination with cisplatin (P) in patients (pts) with metastatic or locally advanced NSCLC. For phase II trials, the recommended dose of each agent administered as a 1 hr infusion was 75 mg/m 2 (Ann. Oncol. 5; P773, 1994). Hydration was started 2 hrs prior to T which was given immediately prior to P and ended 22 hrs post P. Ondansetron and dexamethasone were given as antiemetics. Cycles were repeated each 21 days. Eligibility included locally advanced/metastatic NSCLC, no prior chemotherapy, measurable disease, age 18–75 yrs, WHO performance status (PS) 0–2 and adequate bone marrow, hepatic and renal function. CSF's or prophylactic antibiotics were not permitted. Interim results, as analysed on 9/3/95 are reported. Baseline characteristics for the 47 eligible patients (2 pts with Stage 1 disease were excluded from response analysis) were median age 60 (range 36–74) years, PS 1/2 of 61%/22% and Stage III/IV, 37%/63% pts respectively. All pts were evaluable for toxicity but only eligible pts completing 2 cycles of chemotherapy were evaluable for response. In 36 evaluable pts, the partial response (PR) rate was 33% (12/36 pts), SD 44% (16/36 pts) and PD 22% (8/36 pts). Of the 12 PR's, 6 have been confirmed on subsequent CT scans. Grade 4 toxicities included febrile neutropenia (3 pts), neutropenia (31 pts) and diarrhea (5 pts). Grade 3 or 4 nausea/vomiting was seen in 10 pts. Other toxicities requiring dose reductions or discontinuation of study medication included cardiac abnormalities (2 pts) and fluid retention (2 pts). There were 9 hypersensitivity reactions. There was 1 toxic death (infection and neutropenia). Although significant toxicities were observed, these were manageable. Final results will be presented. The combination of docetaxel and cisplatinum has significant activity in NSCLC although does not appear to be substantially better than T alone. Toxicity may preclude phase III evaluation.

Two cases of small cell carcinoma of the lung in which flare responses were demonstrated are discussed. Although the primary tumor and extraskeletal metastases responded to first-line chemotherapy, bone scintigraphs performed 3 months after the start of treatment suggested tumor progression. However, following repeat bone imaging and subsequent clinical evaluation, the interim scintigraphs appeared to represent an unusual flare response, in which the activity of pre-existing hot spots increased and new lesions developed.

There has been recent concern about both the care of dying patients and the adequacy of the preparation that most doctors receive for this task. The role of the doctor in palliative care is discussed and the educational needs of medical students in palliative care are suggested. A palliative care course for fifth-year students at the Austin Hospital-Repatriation General Hospital Clinical School, University of Melbourne, is described. This course recently has been adopted by the Victorian Palliative Care Council as a model for undergraduate palliative medicine education, and has been recommended to the University of Melbourne and Monash University Medical Schools for incorporation in each Clinical School curriculum.