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Background: Enco + cetux (doublet) has been approved in the US, EU, and Japan for the treatment of BRAF V600E-mutant mCRC after progression on 1-2 prior regimens. In the BEACON CRC study (NCT02928224), median OS (95% CI) with the doublet was 9.3 months (8.0-11.3) vs 5.9 months (5.1-7.1) with cetux + irinotecan or FOLFIRI (control) in patients (pts) with BRAF V600E-mutant mCRC (HR 0.61 [95% CI: 0.5-0.8]). This post hoc analysis investigates OS by prior therapies to the doublet treatment in pts with BRAF V600E-mutant mCRC from the BEACON CRC study. Methods : OS of pts treated with the doublet or control were compared according to prior treatment with bevacizumab, oxaliplatin or FOLFOXIRI and duration of prior anticancer therapy (ACT). Results : Sixty-four per cent and 55% of pts in the doublet and control arm respectively received prior bevacizumab. Of pts who had one prior therapy, 95% and 88% received prior oxaliplatin and 20% and 14% received prior FOLFOXIRI, respectively. In the doublet arm, pts who had bevacizumab < 4 months before start of study treatment had a median OS of 8.3 months (95% CI: 6.2-11.2); those who had bevacizumab >=4 months prior had a median OS of 10.7 (95% CI: 7.5-17.7). Within each treatment arm, OS was similar regardless of prior treatment with oxaliplatin or FOLFOXIRI. The duration of prior ACT was similar across study arms, ranging from 5.6 to 5.8 months for the first line of ACT. Conclusions : In the BEACON CRC study, pts treated with the doublet for BRAF V600E-mutant mCRC demonstrated similar OS regardless of prior therapies or duration of prior therapy use. This exploratory post hoc analysis provides data that reflect the prior treatment landscape clinicians may face when deciding subsequent treatment regimens for pts with BRAF V600E-mutant mCRC.

Background: In the BEACON study, encorafenib + binimetinib + cetuximab (enco/bini/cetux; triplet) and enco + cetux (doublet) improved OS and ORR vs standard of care in previously treated BRAF V600E-mutant mCRC pts. Molecular profiling of tumours from this study was performed to identify molecular correlates of outcome. Methods : Baseline tumour samples were analysed by whole-exome sequencing (WES) and whole transcriptome sequencing (WTS). BRAF-mutant (BM) and consensus molecular subtypes (CMS) were determined and pathway activities evaluated with gene set variation analysis. Tumour response was evaluated for each subtype. Additional association and interaction analyses between molecular features and outcomes by treatments are ongoing and will be presented. Results : Baseline tumour samples were analysed by WES and/or WTS for 79.2% of pts. Of the 460 pts analysed by WTS (73.7% in the triplet arm, 66.4% in the doublet arm, 67.4% in the control arm), 84.6% were classified as CMS1 or CMS4. Overall 32.2% of pts were classified as BM1 and the majority (84.5%) of these were CMS4. Many of those classified as BM2 (67.8%) were CMS1 (64.7%). In the BM1 and CMS4 tumours, expression of inflammatory response and epithelial mesenchymal transition genes were elevated, and expression of cell cycle genes was reduced. Response rate in pts with CMS4 and/or BM1 tumors was higher in the triplet arm (CMS4: 33.3% [95% CI: 21.7-46.7]; BM1: 33.3% [95% CI: 21.4-47.1]) vs the doublet arm (CMS4: 19.2% [95% CI: 9.6-32.5]; BM1: 14.9% [95% CI: 6.2-28.3]). Conclusions : Molecular characteristics and biological properties observed in BRAF V600E-mutant mCRC suggest a subset of pts with specific molecular features may derive greater clinical benefit from triplet vs doublet therapy. These findings support further investigating the biological landscape in BRAF-mutant mCRC to enable potential hypotheses for pt selection to improve clinical outcome in future studies.

Background: Unresectable locally advanced pancreatic cancer (LAPC) is generally managed with chemotherapy or chemoradiotherapy, but prognosis is poor with a median survival of ~13 months (or up to 19 months in some studies). We assessed a novel brachytherapy device, using phosphorous-32 (32P) microparticles, combined with standard-of-care chemotherapy. Patients and Methods: In this international, multicentre, single-arm, open-label pilot study, adult patients with histologically or cytologically proven unresectable LAPC received 32P microparticles, via endoscopic ultrasound-guided fine-needle implantation, planned for week 4 of 5-fluorouracil, leucovorin, irinotecan and oxaliplatin (FOLFIRINOX) or gemcitabine/nab-paclitaxel chemotherapy, per investigator's choice. The primary endpoint was safety and tolerability measured using Common Terminology Criteria for Adverse Events version 4.0. The lead efficacy endpoint was local disease control rate at 16 weeks. Result(s): Fifty patients were enrolled and received chemotherapy [intention-to-treat (ITT) population]. Forty-two patients received 32P microparticle implantation [per protocol (PP) population]. A total of 1102 treatment-emergent adverse events (TEAEs) were reported in the ITT/safety population (956 PP), of which 167 (139 PP) were grade >=3. In the PP population, 41 TEAEs in 16 (38.1%) patients were possibly or probably related to 32P microparticles or implantation procedure, including 8 grade >=3 in 3 (7.1%) patients, compared with 609 TEAEs in 42 (100%) patients attributed to chemotherapy, including 67 grade >=3 in 28 patients (66.7%). The local disease control rate at 16 weeks was 82.0% (95% confidence interval: 68.6% to 90.9%) (ITT) and 90.5% (95% confidence interval: 77.4% to 97.3%) (PP). Tumour volume, carbohydrate antigen 19-9 levels, and metabolic tumour response at week 12 improved significantly. Ten patients (20.0% ITT; 23.8% PP) had surgical resection and median overall survival was 15.2 and 15.5 months

Background: BEACONCRC is a randomized, phase 3 study which evaluated the triplet of encorafenib (ENCO) + binimetinib (BINI) + cetuximab (CETUX) and the doublet of ENCO + CETUX vs. investigator's choice of irinotecan + CETUX or FOLFIRI + CETUX in patients (pts) with BRAFV600E metastatic colorectal cancer (mCRC) whose disease had progressed after 1-2 prior regimens in the metastatic setting. Primary endpoints were overall survival (OS) and objective response rate (ORR; by blinded central review) for triplet vs control. In a previous interim analysis, triplet and doublet improvedOS andORRversus standard of care. Here we report on an updated analysis. Method(s): Updated analysis includes 6 months of additional follow-up and response data for all randomized pts. The study is ongoing. Result(s): Patients received triplet (n = 224), doublet (n = 220), or control (n = 221). Median OS was 9.3 months (95% confidence interval [CI]:8.2, 10.8) for triplet and 5.9 months (95% CI:5.1-7.1) for control (hazard ratio [HR] (95% CI): 0.60 (0.47-0.75)). Median OS for doublet was 9.3 months (95% CI: 8.0-11.3) (HR vs control: 0.61 (0.48- 0.77). Confirmed ORR was 26.8% (95% CI: 21.1%-33.1%) for triplet, 19.5% (95% CI: 14.5%-25.4%) for doublet, and 1.8% (95% CI: 0.5%- 4.6%) for control. Retrospective subgroup analyses suggested some pts may benefit more from triplet than doublet therapy (Table). Both triplet and doublet showedimprovedOS compared to control in all subgroups. Adverse events were consistent with prior analysis, with grade >=3 adverse events in 65.8%, 57.4%, and 64.2% for triplet, doublet and control, respectively. Conclusion(s): The updated analysis of the BEACON CRC study confirmed that encorafenib + cetuximab with or without binimetinib improved OS and ORR in previously treated pts with BRAF V600E mCRC compared with standard chemotherapy.

Background: LAPC is associated with a poor prognosis. Current standard treatment is limited to chemotherapy or chemoradiotherapy. P-32 Microparticles is a brachytherapy device that implants a predetermined dose of P-32 into pancreatic tumours via endoscopic ultrasound (EUS) guidance. This reports the initial results of a pilot study in combination with chemotherapy. Method(s): Eligible patients were permitted to receive either GNP or FOLFIRINOX. P-32 was implanted at week 4 or 5. The dose of P-32 was calculated from tumour volume to deliver an absorbed dose of 100 Gy. Diffusion pattern of the P-32 suspension was assessed by EUS and bremsstrahlung SPECT/CT imaging. Safety data was graded using CTCAE v4.0 criteria. Response was assessed according to RECIST 1.1 with CT scans every 8 weeks and FDG-PET scans at baseline and week 12. Result(s): 50 patients were enrolled (Intent-to-Treat population (ITT)) of which 42 were implanted with the device (Per Protocol population (PP)). 10 received FOLFIRINOX and 40 GNP. Median age was 65, 28 were male and all had a PS 0/1. 1070 adverse events (ITT) were reported; 153 (80% of patients) were >= Grade 3. The most common AEs of >= Grade 3 were haematological (39, 46%) and gastrointestinal disorders (30, 34%). No serious device-or radiation-related toxicities have been reported. PP Local Disease Control Rate at Week 16 was 90%; 95% CI: 77-97% and at Week 24 was 71%; 95% CI: 55-84%. Overall Response Rate (ORR) was 31%; 95% CI: 18-47%. Median change in tumour volume from Baseline to Week 16 and to Week 24 was-38% (range +89% to-90%) and-27.5% (range +139% to-79%). Ten (24%) patients underwent surgical resection following repeat staging. Eight patients had R0 margin. Conclusion(s): The use of EUS-guided implantation of P-32 is feasible, with an acceptable safety profile in combination with first-line chemotherapy for LAPC patients. Encouraging OR and DCR are observed. Further follow-up to inform results of local progression free survival

BACKGROUND: The Short Course Oncology Therapy (SCOT) study is an international, multicentre, non-inferiority randomised controlled trial assessing the efficacy, toxicity, and cost-effectiveness of 3 months (3 M) versus the usually given 6 months (6 M) of adjuvant chemotherapy in colorectal cancer. METHOD(S): In total, 6088 patients with fully resected high-risk stage II or stage III colorectal cancer were randomised and followed up for 3-8 years. The within-trial cost-effectiveness analysis from a UK health-care perspective is presented using the resource use data, quality of life (EQ-5D-3L), time on treatment (ToT), disease-free survival after treatment (DFS) and overall survival (OS) data. Quality-adjusted partitioned survival analysis and Kaplan-Meier Sample Average Estimator estimated QALYs and costs. Probabilistic sensitivity and subgroup analysis was undertaken. RESULT(S): The 3 M arm is less costly (-4881; 95% CI: -6269; -3492) and entails (non-significant) QALY gains (0.08; 95% CI: -0.086; 0.230) due to a better significant quality of life. The net monetary benefit was significantly higher in 3 M under a wide range of monetary values of a QALY. The subgroup analysis found similar results for patients in the CAPOX regimen. However, for the FOLFOX regimen, 3 M had lower QALYs than 6 M (not statistically significant). CONCLUSION(S): Overall, 3 M dominates 6 M with no significant detrimental impact on QALYs. The results provide the economic case that a 3 M treatment strategy should be considered a new standard of care.Copyright © 2018, The Author(s).

BACKGROUND: The Short Course Oncology Therapy (SCOT) study is an international, multicentre, non-inferiority randomised controlled trial assessing the efficacy, toxicity, and cost-effectiveness of 3 months (3 M) versus the usually given 6 months (6 M) of adjuvant chemotherapy in colorectal cancer. METHODS: In total, 6088 patients with fully resected high-risk stage II or stage III colorectal cancer were randomised and followed up for 3-8 years. The within-trial cost-effectiveness analysis from a UK health-care perspective is presented using the resource use data, quality of life (EQ-5D-3L), time on treatment (ToT), disease-free survival after treatment (DFS) and overall survival (OS) data. Quality-adjusted partitioned survival analysis and Kaplan-Meier Sample Average Estimator estimated QALYs and costs. Probabilistic sensitivity and subgroup analysis was undertaken. RESULTS: The 3 M arm is less costly (-£4881; 95% CI: -£6269; -£3492) and entails (non-significant) QALY gains (0.08; 95% CI: -0.086; 0.230) due to a better significant quality of life. The net monetary benefit was significantly higher in 3 M under a wide range of monetary values of a QALY. The subgroup analysis found similar results for patients in the CAPOX regimen. However, for the FOLFOX regimen, 3 M had lower QALYs than 6 M (not statistically significant). CONCLUSIONS: Overall, 3 M dominates 6 M with no significant detrimental impact on QALYs. The results provide the economic case that a 3 M treatment strategy should be considered a new standard of care.

BACKGROUND: 6 months of oxaliplatin-containing chemotherapy is usually given as adjuvant treatment for stage 3 colorectal cancer. We investigated whether 3 months of oxaliplatin-containing chemotherapy would be non-inferior to the usual 6 months of treatment. METHODS: The SCOT study was an international, randomised, phase 3, non-inferiority trial done at 244 centres. Patients aged 18 years or older with high-risk stage II and stage III colorectal cancer underwent central randomisation with minimisation for centre, choice of regimen, sex, disease site, N stage, T stage, and the starting dose of capecitabine. Patients were assigned (1:1) to receive 3 months or 6 months of adjuvant oxaliplatin-containing chemotherapy. The chemotherapy regimens could consist of CAPOX (capecitabine and oxaliplatin) or FOLFOX (bolus and infused fluorouracil with oxaliplatin). The regimen was selected before randomisation in accordance with choices of the patient and treating physician. The primary study endpoint was disease-free survival and the non-inferiority margin was a hazard ratio of 1·13. The primary analysis was done in the intention-to-treat population and safety was assessed in patients who started study treatment. This trial is registered with ISRCTN, number ISRCTN59757862, and follow-up is continuing. FINDINGS: 6088 patients underwent randomisation between March 27, 2008, and Nov 29, 2013. The intended treatment was FOLFOX in 1981 patients and CAPOX in 4107 patients. 3044 patients were assigned to 3 month group and 3044 were assigned to 6 month group. Nine patients in the 3 month group and 14 patients in the 6 month group did not consent for their data to be used, leaving 3035 patients in the 3 month group and 3030 patients in the 6 month group for the intention-to-treat analyses. At the cutoff date for analysis, there had been 1482 disease-free survival events, with 740 in the 3 month group and 742 in the 6 month group. 3 year disease-free survival was 76·7% (95% CI 75·1-78·2