Purpose/Objective(s) Radiotherapy for CCA remains an area of research. ABC-07 [ISRCTN: 10639376] is a randomized trial (1:2 randomization) for newly diagnosed, inoperable, locally advanced CCA (n = 69), comparing 8 cycles of Gemcitabine/Cisplatin (GC) vs 6 cycles GC plus SBRT to the tumor (50 Gy in 5 fractions (Fr)). The primary endpoint of improving progression free survival was not met. Here, we examine the influence of BED, alongside patient and cancer variables, on disease outcomes. Materials/Methods 45 patients were randomized to SBRT, of which 41 received SBRT. The protocol specified longer fractionation (67.5 Gy in 15 Fr) for larger tumors (>6cm, max 12cm) or inclusion of nodal disease. Reduced dose thresholds (45 Gy then 40 Gy in 5 Fr; 58.1 Gy then 45 Gy in 15 Fr) were specified to meet mean liver dose constraints. PTV D95% values (min dose (Gy) to 95% of planning target volume (PTV)) were extracted from DICOM plans and converted to BED (α/β = 10Gy) (termed PTV_D95%BED). Other predictor variables included were: age, performance status (PS), female sex, biliary stent in-situ, T-stage (3-4 vs 1-2), N-stage (1 vs 0), distal CCA (dCCA), PTV Volume (PTV_vol). PTV D95% association with overall survival (OS), progression free survival (PFS) and time to local progression (TLP) was initially tested by univariate Cox and visualized by Kaplan-Meier. Multivariate Cox models were fitted for each endpoint, fitting PTV_D95%BED and other predictor variables, using backward stepwise selection using p<0.2. For TLP, as all variables removed, p<0.3 was used instead. Results PTV volumes were median 65cc (range 21.5 – 498cc). PTV_D95%BED doses were median 72 Gy (IQR 57 – 100 Gy BED). Planned fractionation was 5 Fr (n = 30) or 15 Fr (n = 11). PTV volume vs PTV_D95%BED showed no correlation = -0.0003. By univariate Cox, PTV_D95%BED did not meet p<0.05 threshold against OS (HR 0.989, P = 0.36), PFS (HR 0.982, P = 0.068) or TLP (HR 0.980, P = 0.26). Multivariate model selected variables were: OS model: PS (HR 0.3, p 0.02), N-stage (HR 2.1, p 0.13), PTV_vol (HR 0.98, p 0.037); PFS model: D95%BED (HR 0.98, p 0.047), age (HR 0.96, p 0.054), PTV_vol (HR 0.997, p 0.17); Local progression model: D95%BED (HR 0.96, p 0.14), age (HR 0.94, p 0.18), dCCA (HR 0.27, p 0.25), T-stage3/4 (HR 2.5, p 0.24), PTV_vol (HR 0.995, p 0.21). Conclusion We believe this phase II prospectively collected trial data shows a signal of dose effect in subsequent CCA outcomes. There appears to be no correlation with patient or cancer related variables. Models for prediction of tumor coverage should be incorporated into treatment pathway diagnostics; enabling selection of best candidates for SBRT. Better understanding of tumor biology would also aid in selecting patients where local control is more critical (i.e. lower metastatic propensity).

Metastatic pancreatic adenocarcinoma (mPDAC) has a poor prognosis with a 5-year survival rate of 3%. In non-metastatic, unresectable locally advanced pancreatic cancer (LAPC) patients, endoscopic-ultrasound (EUS)-guided intra-tumoral phosphorus-32 ( 32 P)-microparticles implantation resulted in local disease control rate [LDCR] (defined as Stable Disease [SD] or better) at 16 weeks (3 months post-implantation) of 90.5%. This is the first multicentre analysis of 32 P-microparticles implantation in patients with mPDAC. Patients with mPDAC treated with chemotherapy and intratumoural 32 P-microparticles (OncoSil™; OncoSil Medical) delivering 100Gy target tumour absorbed dose from 5 centres in Australia and UK were retrospectively analysed. Patients received 32 P-microparticles in the PanCO study (metastases identified post-enrolment by PET-imaging) or special access scheme. 14 patients were treated (male: 50%; median age: 64.5 years; ECOG 0/1/2: 21.4%/57.1%/21.4%). Median primary tumour longest diameter [LD] and volume were 40.5mm and 21.8cm 3, respectively. Patients had a median of 3 metastases (range, 1-7) in liver (42.9%), lung (35.7%), liver/lung (7.1%), liver/peritoneum (7.1%) or lung/peritoneum (7.1%). Patients received chemotherapy (FOLFIRINOX [n=4; 1 2 nd -line] or gemcitabine/nab-paclitaxel [n=10; 2 2 nd -line]). 32 P-microparticles were implanted at median 3.1 months from initial chemotherapy commencing [baseline], 7 patients at median 1.1 months (range, 0.7-2.5 [early cohort]) and 7 at median 4.9 months (range, 3.6-7.9 [delayed cohort]). Pre-implantation, RECIST response was 2 (14.3%) Partial Response [PR], 5 (35.7%) SD, 1 (7.1%) local Progressive Disease [PD] and 2 (14.3%) distant PD; 4 (28.6%) had no intermediate scan. LDCR at 3 months post-implantation was 100%. Best RECIST primary tumour response vs . pre-implantation scan was 4 (28.6%) PR, including the patient with local PD pre-implantation, plus 10 (71.4%) SD. The early implantation cohort had a mean –22.0% (median –25.0%) maximal decrease in primary tumour LD vs . baseline. The delayed implantation cohort had a mean –30.2% (median –25.0%) maximal decrease in primary tumour LD vs . pre-implantation, compared to a mean –8.6% (median –4.2%) pre-implantation decrease vs . baseline. One patient (7.1%) had a good response and thus underwent surgical resection (R0 on histology). Median CA19-9 in patients with baseline >35U/mL decreased from 856.5U/mL to 72U/mL at nadir; 6/10 patients had >50% decrease. Site(s) of first progression post-implantation were: 57.1% distant, 28.6% local/distant, 7.1% local and 7.1% no progression; 2 patients (14.3%) with distant PD developed local PD (5 and 30 months later). Median follow-up was 35.3 months. Although median progression-free survival (PFS) from 32 P-implantation was 5.6 months (95% CI: 4.3-non-calculable [nc]), local PFS was longer than distant PFS (9.4 (95% CI: 5.9-nc) vs . 5.6 (95% CI: 4.3-nc)). From chemotherapy commencement, median overall survival was 13.9 (95% CI: 12.2-nc) months. No Grade 4/5 acute toxicities were observed; 3 (21.4%) patients had device- or procedure-related Grade 1/2 AEs (abdominal pain; nausea; fatigue; dyspepsia) that were also attributed to chemotherapy. EUS-guided 32 P-microparticles implantation to deliver 100Gy to target tumour appears safe in mPDAC patients receiving chemotherapy, with encouraging outcomes including 100% LDCR at 3 months post-implantation. This retrospective analysis highlights the potential clinical benefits, particularly of local tumour control and overall survival, in a metastatic cohort in whom outcomes are often poor.

BRAF mutations occur in 8% to 12% of patients with mCRC and are associated with clinically poor prognosis. E+C was approved by the FDA and EMA for patients with BRAF V600E-mutant mCRC who have received prior systemic therapy based on the results of the BEACON study (NCT02928224), which combined patients treated in the second- (2L) and third-line (3L) setting. Here we evaluate the characteristics and outcomes separately for patients who received 2L and 3L E+C or control. BEACON was a phase 3, open label study evaluating E (300 mg QD) plus C (400 mg/m 2 initial dose followed by 250 mg/m 2 weekly) with or without binimetinib (45 mg BID) vs control (C plus irinotecan or FOLFIRI). The primary study endpoint was OS. For this post hoc analysis (data cutoff: November 10, 2022), patients receiving E+C or control were grouped by line of therapy (2L and 3L). A total of 291 patients received 2L treatment (n=146 E+C; n=145 control); median age was 60 and 59 years, 45.9% and 49.0% had ECOG PS 1, and 45.2% and 44.1% had ≥3 organs involved at baseline. Of those who received 3L treatment (n=74 E+C; n=76), median age was 62 and 61 years, 50.0% and 55.3% had ECOG PS 1, and 50.0% and 44.7% had ≥3 organs involved at baseline. For 2L, the OS HR [95% CI] was 0.60 [0.46, 0.78]; P P P =0.0057 (median OS: 7.9 and 4.8 months for E+C and control); the PFS HR [95% CI] was 0.43 [0.29, 0.66]; P < 0.0001 (median PFS: 4.2 and 1.5 months). In 2L, 31 (21.2%) vs 3 (2.1%) patients for E+C vs control were confirmed responders. For 3L, 14 (18.9%) vs 1 (1.3%) patients for E+C vs control were confirmed responders. Of patients who received 2L treatment, 91 patients (62.3%) in the E+C group, and 77 patients (53.1%) in the control group received subsequent therapy. Of those who received 3L treatment, 35 patients (47.3%) in the E+C group and 34 patients (44.7%) in the control group received subsequent therapy. The most common all-causality AEs (≥30% in the E+C arm) in the 2L (E+C vs control) were diarrhea, nausea, dermatitis acneiform, abdominal pain, and fatigue. In the 3L, these were fatigue, diarrhea, nausea, decreased appetite, and anemia. E+C is an effective treatment regimen for patients with BRAF V600E-mutant mCRC in the 2L and 3L setting. In the BEACON CRC study, patient characteristics and outcomes were generally similar between those who received E+C in 2L and those who received it in 3L. First-line E+C with or without chemotherapy is currently under investigation in the BREAKWATER study (NCT04607421).

This article summarises expert discussion on the management of patients with hepatocellular carcinoma (HCC), which took place during the 24th World Gastrointestinal Cancer Congress (WGICC) in Barcelona, July 2022. A multidisciplinary approach is mandatory to ensure an optimal diagnosis and staging of HCC, planning of curative and therapeutic options, including surgical, embolisation, ablative strategies, or systemic therapy. Furthermore, in many patients with HCC, underlying liver cirrhosis represents a challenge and influences the therapeutic options.

The SCOPE gastrointestinal (GI) program gathered real-world insights on the management of patients with metastatic gastric cancer (mGC), colorectal cancer, and pancreatic cancer. Results on prescribing patterns and treatment decisions in different settings for patients with mGC are reported. An international panel of expert GI oncologists developed the SCOPE GI cancer survey. Healthcare professionals (HCPs) were asked about their management of patients with GC, and their third-line (3L) and fourth-line (4L) treatment decisions for several real-world patient cases. Data were collected at in-person and virtual meetings conducted from July 2021–December 2022. In total, 499 HCPs participated across 17 countries in Europe, the Middle East, and Latin America. The majority (82%) were medical oncologists and practiced in public hospitals/clinics (76%). In total, 93%, 62%, and 52% of HCPs tested for HER2, MMR/MSI, and PD-L1 status at diagnosis, respectively. The main 3L treatment goals were preserving quality of life (QOL; 31%), prolonging overall survival (26%), and relieving symptoms (16%). HCPs reported that 25% of patients refused active treatment in the 3L; the main reasons were deterioration/limitation of daily activities (37%) and concerns regarding efficacy of the current 3L treatment options (36%). When a patient refuses active treatment, 57% of HCPs would explore the reasons and recommend appropriate treatment, if possible, while 38% would accept the patient's decision and opt for best supportive care (BSC). Considering a 63-year-old unfit (ECOG PS 2) patient, pMMR/MSS, HER2 negative, and PD-L1 combined positive score (CPS) 0, who received 1L FOLFOX/5-FU and 2L FOLFIRI, 93% of HCPs stated trifluridine-tipiracil was an appropriate 3L treatment; the main drivers were survival data for 54% of HCPs and QOL for 21% of HCPs. Trifluridine-tipiracil was selected as the 3L treatment of choice (74%) for this patient regardless of whichever 1L or 2L treatments had been administered; the 2 most favored 4L choices were BSC (44%) and trifluridine-tipiracil (21%). If the patient was older (78-year-old), trifluridine-tipiracil remained the preferred 3L treatment (73%), although the proportion of HCPs who would prescribe BSC in 4L increased to 87%. For a fit (ECOG 1) 64-year-old with HER2 and pMMR/MSS negative, PD-L1 CPS 0 disease, who received 1L FOLFOX/5-FU and 2L ramucirumab/paclitaxel, 89% of HCPs stated that trifluridine-tipiracil was an appropriate 3L treatment, driven by the phase III survival data (44%) and QOL (18%). Regardless of the 1L or 2L treatment, trifluridine-tipiracil remained the 3L treatment of choice for this patient. BSC was the preferred 4L treatment (32%) overall, although there was some regional variation with HCPs in Western Europe preferring trifluridine-tipiracil while those in Central/Eastern Europe opted most frequently for irinotecan monotherapy. In mGC, HER2 and MMR/MSI were tested most frequently at diagnosis. PD-L1 testing may increase now, due to availability of immune checkpoint inhibitors in 1L. The main 3L treatment goals were to preserve QOL, prolong survival, and relieve symptoms, which aligned with patients' concerns about deterioration of daily activities. The preferred 3L treatment choice was trifluridine-tipiracil, and BSC was the preferred 4L option.

Introduction: uLAPC has poor prognosis. We report post-hoc analysis of resected vs. non-resected cohorts in a study of beta-radiation-emitting Phosphorous-32 (32P)-microparticles, implanted into tumours via endoscopic-ultrasound (EUS) guidance, and standard-of-care chemotherapy in uLAPC.

The BRAF inhibitor encorafenib, in combination with cetuximab (EC), has recently been approved for patients with BRAFV600E-mutated metastatic colorectal cancer (BRAFV600E-mCRC) after prior systemic therapy. As the combination is the first BRAF inhibitor-based regimen approved for BRAFV600E-mCRC the goal of this analysis was to explore novel and distinctive data visualization outputs to enable a potentially more practical interpretation and prediction of the safety profile of encorafenib + cetuximab and thus better management of adverse events. Adverse Events (AE) of interest (AEI’s), including dermatological AEs, arthralgia/myalgia, nausea/vomiting, diarrhea, abdominal pain, fatigue/asthenia, and nephrotoxicity, were previously defined, examined and published from the EC group of the multicenter, randomized, phase 3 BEACON study. The presence of AE, time to AE onset and time to AE resolution were investigated and their association with clinical characteristics (age, gender) were explored using data visualization including stacked bars, multistate models’ visualization, bubble timeline analysis, boxplots, heatmap graphs and infographics based unsupervised machine learning results. Representation with a bubble timeline analysis provides visual advantages to ease interpretation, within the same graph, the frequency of AEI occurrence, the grades of AEI, time to onset and/or time to resolution, depending on each AEI category. This aids a global overview and linkage patterns of safety and timelines. This analysis was conducted on 216 patients in the BEACON study treated with EC. The most commonly occurring AEI were dermatological toxicity (75.5%), arthralgia/myalgia (56.0%) and fatigue/asthenia (56.0%) with most AEI being Grade 1 or 2. The probability of experiencing AEI was higher in women than in men, especially for arthralgia/myalgia (W:65,4%; M: 47,3%), abdominal pain (W: 43,3%; M: 26,8%), and nausea/vomiting (W: 55,8%; M: 38,4%). However, the observed median onset time was 2 weeks earlier for men for abdominal pain and arthralgia/myalgia. Bubble timeline analysis highlight dermatological toxicities, nausea/vomiting and fatigue occur sooner than other AEI types (respective median onset time (in weeks): 2.4, 2.3, 2.0), and that nausea/vomiting, diarrhea and abdominal pain resolve faster (respective median recovery time (in weeks): 0.8, 0.7 and 1,8 weeks. Multistate models were tested to provide a visualization of the evolution of probability of onset and probability of recovery for each AEI groups since the inclusion. For dermatological toxicity, the highest probability of onset was between 2 and 3 months (38% at 3 months). Patients who experienced a first dermatological AE had less chance to develop a second one (at 3 months, probability of 15% vs 54%). Additional analyses will be presented at the meeting. This novel approach allows a more nuanced perspective and approach to understanding AEI patterns, including linking disparate AE’s. This type of visualization can help heath care givers to better predict EC side effects which is generally well tolerated in most patients, with most AEIs being mild to moderate in severity. Analyses providing novel visual aids to support the interpretation of safety profiles of EC should help oncologists and heath care givers in daily clinical practice to improve overall outcomes for patients.

Results: APE1 was overexpressed in CRC tissues compared to paired normal tissue at the mRNA and protein levels.Overexpression of APE1 was significantly associated with advanced stage, lymphovascular invasion, perineural invasion, deeper tumor invasion, lymph node metastasis, distant metastasis, and poor survival.Multivariate analysis demonstrated that APE1, perineural invasion and lymph node metastasis were the independent prognostic factors associated with overall survival.The mean Ki-67 labeling index value of APE1-positive tumors was significantly higher than that of APE1-negative tumors.However, there was no significant difference between APE1 expression and the apoptotic index or microvessel density.Conclusions: These findings indicate that overexpression of APE1 is significantly associated with tumor progression and poor survival in CRC patients.Therefore, APE1 may be a novel biomarker and present a potential prognostic factor for CRC.

The SCOPE gastrointestinal (GI) cancers program was designed to gather real-world clinical insights on the management of patients with metastatic gastric cancer, colorectal cancer, and pancreatic cancer (mPaCa). Herein, practice patterns for patients with unresectable or resectable mPaCa are reported. The SCOPE survey was developed by an expert panel of GI oncologists. Healthcare professionals (HCPs) were asked about treatment choices and drivers for first- (1L) and second- (2L) line patient scenarios. Due to different treatment paradigms, HCPs from Japan were only queried about practice patterns for patients with resectable mPaCa. Participants were asked to choose their answers from a list of options predefined by the expert panel. Data were collected at in-person or virtual meetings. Between July 2021 and December 2022, there were 762 respondents from 13 countries across Europe, South America, and Japan. Of these, 53% were medical oncologists, 20% were internists, and 19% were surgeons, with HCPs from the last 2 specialties exclusively based in Japan; 83% of HCPs worked in a public setting. HCPs outside of Japan were asked how they treat 1L patients with unresectable stage IV, BRCA wildtype mPaCa. The most favored treatments were Gem-NabP (50%) and FOLFIRINOX/mFOLFIRINOX (45%); the main driver was to improve overall survival (OS; Gem-NabP: 71%; FOLFIRINOX/mFOLFIRINOX: 72%). If the patient had BRCA-mutated vs wildtype mPaCa, FOLFIRINOX/mFOLFIRINOX (43%) and Gem-platinum (36%) were the treatments of choice, while only a small proportion of HCPs (11%) would choose Gem-NabP. In the 2L setting, if a patient had first received Gem-NabP treatment, 68% of HCPs chose Nal-Iri + 5-FU-LV as their preferred treatment; improving OS (57%) was the main goal, followed by preserving quality of life (QOL; 23%). If, alternatively, the patient had received 1L FOLFIRINOX/mFOLFIRINOX treatment and experienced grade 2 neurotoxicity, the 2L choice shifted to gemcitabine monotherapy (42%). All HCPs, including those from Japan, were asked how they would treat a patient with resectable stage II mPaCa that relapsed after 5-month treatment-free interval following adjuvant treatment with mFOLFIRINOX. Gem-NabP was the preferred 1L treatment choice in the metastatic setting (78%); improving OS was the main driver (70%), followed by preserving QOL (12%). If the patient had received Gem-NabP in 1L, Nal-Iri + 5-FU-LV was the preferred 2L treatment choice (80%); the main goals were improving OS (52%), preserving QOL (21%), and stabilizing disease (11%). For all HCPs, the main consideration when choosing a 2L treatment for a patient with resectable mPaCa was performance status (72%). In line with international guidelines for mPaCa, Gem-NabP and FOLFIRINOX/mFOLFIRINOX were the preferred 1L treatment options, and Nal-Iri + 5-FU-LV was the treatment of choice for 2L patients who had progressed on Gem-based regimens. The main drivers behind 1L and 2L treatment choices were improving OS and preserving QOL.

BACKGROUND:In the BEACON CRC study (NCT02928224), encorafenib plus cetuximab with binimetinib {9.3 versus 5.9 months; hazard ratio (HR) [95% confidence interval (CI)]: 0.60 [0.47-0.75]} or without binimetinib [9.3 versus 5.9 months; HR (95% CI): 0.61 (0.48-0.77)] significantly improved overall survival (OS) compared with the previous standard of care (control) in patients with BRAF V600E metastatic colorectal cancer (mCRC). Quality of life (QoL) was a secondary endpoint, assessed using validated instruments. PATIENTS AND METHODS:BEACON CRC was a randomized, open-label, phase III study comparing encorafenib plus cetuximab with or without binimetinib and the investigator's choice of irinotecan plus cetuximab or FOLFIRI plus cetuximab (chemotherapy control) in patients with previously treated BRAF V600E mCRC. Patient-reported QoL assessments included the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC) and Functional Assessment of Cancer Therapy-Colorectal (FACT-C). The primary outcome for these tools was time to definitive 10% deterioration. RESULTS:Encorafenib plus cetuximab, both with and without binimetinib, was associated with longer median times to definitive 10% deterioration versus the control group in the EORTC Global Health Status scale [HR (95% CI): 0.65 (0.52-0.80) versus 0.61 (0.49-0.75), respectively] and the FACT-C functional well-being subscale [HR (95% CI): 0.62 (0.50-0.76) versus 0.58 (0.47-0.72), respectively]. Consistent results were observed across all subscales of the EORTC and FACT-C instruments. QoL was generally maintained during treatment for the global EORTC and FACT-C scales. CONCLUSIONS:In addition to improving OS, encorafenib plus cetuximab with or without binimetinib delays QoL decline in previously treated patients with BRAF V600E-mutant mCRC.

14 Background: Our phase II randomized study was conducted in patients with previously untreated unresectable mCRC not eligible to receive standard oxaliplatin- or irinotecan- based chemotherapy regimens. The results of the primary study analysis were reported earlier and demonstrated a promising efficacy in terms of progression-free survival (PFS) and an acceptable safety profile for the combination of trifluridine/tipiracil + bevacizumab (E. Van Cutsem et al. Ann. Oncol. 2020). Here we present the final end-of-study analysis on the overall survival (OS). Methods: Eligible patients were randomized in 1:1 ratio to receive either trifluridine/tipiracil administered orally at 35 mg/m²/dose bid from days 1-5 and days 8-12, and bevacizumab at 5 mg/kg on days 1 and 15 of a 28-day treatment cycle (TT-B), or capecitabine administered orally at 1250 or 1000 mg/m²/dose bid (according to the patient’s status) from days 1-14 and bevacizumab at 7.5 mg/kg on day 1 of a 21-day treatment cycle (C-B). Cycles were repeated until documented disease progression, unacceptable toxicity, or investigator’s/patient’s decision. Following the treatment discontinuation, all patients were followed for OS until the end-of-study, which was defined as the date of the withdrawal visit for the last patient. In the absence of death confirmation or for patients alive as of the end-of-study date, survival time was censored at the date of their last study follow-up. For the OS analysis the HR and the corresponding 2-sided 80% and 2-sided 95% CIs for TT-B versus C-B were estimated using a Cox proportional hazard model adjusting for the stratification factors based on IWRS data. OS was summarized using Kaplan-Meier curves and further characterized in terms of the median and survival probabilities at 6, 12, 18, and 24 months along with the corresponding 2-sided 80% and 2-sided 95% CI (Brookmeyer and Crowley CI for median and Kalbfleisch and Prentice CI for survival probabilities). Results: From April 2016 to March 2017, 153 patients were randomized and followed until end-of-study on September 1, 2020. Twenty-one patients, 11 from TT-B and 10 from C-B, were alive and censored for the analysis. Median OS was 22.31 months in TT-B and 17.67 months in C-B with HR 0.78 (95% CI, 0.55, 1.10). Survival probability at 18 months in TT-B was 0.62 (95% CI, 0.50, 0.72), and 0.47 (95% CI, 0.35, 0.57) in C-B. Conclusions: Our study demonstrated earlier a median PFS of 9.2 months for TT-B and 7.8 months for C-B when administered to patients with previously untreated unresectable mCRC ineligible for standard combination chemotherapy. The final study analysis performed on OS, the main secondary endpoint, provided further evidence for TT-B as a noteworthy valuable regimen in this population settings. Clinical trial information: NCT02743221.

Although the majority of colorectal cancer (CRC) diagnoses occur in adults ≥50 years old (y), there has been a rise in CRC diagnoses in adults BRAF V600E-mutant metastatic CRC (mCRC). This subanalysis evaluates the effect of age on survival, QoL, and safety in patients from BEACON CRC. BEACON CRC was a randomized, open-label, phase 3 study comparing enco+cetux±bini and investigator’s choice of irinotecan+cetux or FOLFIRI+cetux (control) in patients with previously treated BRAF V600E-mutant mCRC. PFS, OS, patient-reported QoL, and safety were assessed by age at enrollment (< 50 or ≥50 y). QoL was measured using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (QLQ-C30) and Functional Assessment of Cancer Therapy-Colorectal (FACT-C). The Kaplan–Meier method was used to calculate median PFS and OS with 95% confidence intervals (CIs) for each subgroup. For OS, Cox proportional hazards models were used to estimate the hazard ratio (HR) with 95% CI. Patients in each treatment arm were stratified by age: < 50 y (enco+cetux+bini, n=47/224; enco+cetux, n=33/220; control, n=49/221) and ≥50 y (enco+cetux+bini, n=177/224; enco+cetux, n=187/220; control, n=172/221). Median (95% CI) PFS by age < 50 y and ≥50 y, respectively, for enco+cetux+bini was 5.0 (3.94–5.55) and 4.4 (4.17–5.55) months; for enco+cetux, 4.3 (2.92–6.01) and 4.3 (4.04–5.52) months; and for control, 1.5 (1.05–1.58) and 1.6 (1.48–2.20) months. Median OS (95% CI) by age < 50 y and ≥50 y, respectively, for enco+cetux+bini was 9.8 (7.56–12.48) and 9.0 (8.02–11.73) months; for enco+cetux, 10.3 (7.26–not reached) and 8.8 (7.89–11.24) months; and for control, 5.4 (3.75–8.90) and 6.4 (5.09–7.39) months. Within each treatment group, OS was similar between age groups: HR (95% CI) for enco+cetux+bini, 0.92 (0.60–1.40); enco+cetux, 0.63 (0.37–1.08); control, 1.24 (0.85–1.80). Mean changes from baseline in QLQ-C30 and FACT-C scores were similar within the same treatment group, regardless of age. Overall, the incidence and severity of adverse events (AEs) were similar within treatment groups, regardless of age; for enco+cetux, there were fewer grade 3/4 AEs in the < 50 y group (39.4%) than in the ≥50 y group (60.7%). In this subanalysis of BEACON CRC, OS was similar between age groups for patients with BRAF V600E-mutant mCRC. Patients < 50 y had fewer grade 3/4 AEs in the enco+cetux group. This subanalysis is limited by the low number of patients. Further analyses are warranted to compare these age groups when treated with targeted therapies for mCRC.

Unresectable LAPC has a poor prognosis. Current standard-of-care (SoC) is limited to chemotherapy or chemo-radiotherapy. Brachytherapy using a device containing beta-radiation-emitting Phosphorous-32 (P-32) microparticles is implanted directly into pancreatic tumours via endoscopic-ultrasound (EUS) guidance. We report a post-hoc analysis of resected vs. non-resected cohorts in PanCO, a single-arm, multi-centre, pilot study of P-32 microparticles with SoC chemotherapy in patients with unresectable LAPC.

The ABC-06 clinical trial stablished ASC+mFOLFOX as the standard of care treatment after Cisplatin and Gemcitabine (CisGem) for ABC. Within the ABC-06 study, patients (pts) diagnosed with ABC (cholangiocarcinoma, gallbladder or ampullary cancer) with progression after CisGem were randomised (1:1) to ASC+mFOLFOX or ASC. Tumour markers (CA19.9, CEA and CA125), were scheduled at baseline (BSL) and at every follow-up visit. This post-hoc analysis explored if changes (stable/reducing vs increasing) of Ca19.9 at week 4 from initiation of ASC+mFOLFOX was associated with radiological progression-free survival (PFS). Secondary end-points included impact of raised BSL Ca19.9 (defined as x1.5 ULN) and chemotherapy-induced changes on overall survival (OS). CEA and CA125 were also analysed. Out 162 pts randomised, BSL Ca19.9 data was available for 135 pts. Paired BSL and week-4 Ca19.9 data was available for 37 pts in the ASC+mFOLFOX arm: Ca19.9 was stable/reducing in 17 (45.9%) and increasing in 20 pts (54.1%). Stable/reducing Ca19.9 showed a numerically longer median radiological PFS (4.3 months (m) vs 3.3m) but differences did not reach statistical significance (HR 1.08 (95% CI 0.55-2.14); p=0.81). When restricted to patients with raised BSL Ca19.9 (23 pts), impact on PFS was more marked (5.7m vs 3.2m), but remained non-significant (HR 1.68 (95% CI 0.70-4.01); p=0.23). Stable/reducing Ca19.9 at week 4 did not impact significantly on OS (p=0.56 (regardless of BSL Ca19.9 level; 37 pts); p=0.84 (if raised BSL Ca19.9; 23 pts)). Raised BSL Ca19.9 was associated both with shorter unadjusted clinical median PFS (3.2m vs 5.0m; HR 1.53 (95% CI 1.05-2.23); p=0.027) and unadjusted OS (4.4m vs 6.4m; HR 1.97 (95% CI 1.33-2.93); p When Cox Regression model (120 pts) for OS exploring the prognostic roles of raised BSL Ca19.9, CEA and CA125 was adjusted for pre-defined stratification factors (platinum sensitivity, albumin, and stage) and randomised trial arm, each raised tumour marker had an independent impact (HR 1.56 (95% CI 1.03 to 2.35); p=0.03 / HR 1.60 (95% CI 1,06 to 2.43) p=0.026 / HR 1.70 (95% CI 1.13 to 2.56); p=0.011 for Ca19.9, CEA and CA125, respectively). Unadjusted median OS was 8.9m if all tumour markers at BSL were non-raised, and 7.0m, 4.0m, 3.2m in the event of having 1, 2 or 3 raised BSL tumour markers. For ABC patients treated with second-line ASC+mFOLFOX, utility of Ca19.9 measured at week-4 after chemotherapy initiation is limited; raised BSL Ca19.9, CEA and CA125 have independent prognostic roles and future studies may need to consider these (individually or pooled) as stratification factors.

Approximately 10% of patients with metastatic colorectal cancer (mCRC) have BRAF mutations, predominantly V600E. Encorafenib has been approved in combination with cetuximab in the US and the EU, and in combination with cetuximab with or without binimetinib in Japan, for the treatment of BRAF V600E-mutant mCRC after prior systemic therapy based on results from the BEACON CRC trial. The trial evaluated encorafenib plus cetuximab with or without binimetinib (triplet or doublet, respectively) versus investigators’ choice of irinotecan or FOLFIRI plus cetuximab (control). 1 First-line treatment options for patients with BRAF V600E-mutant mCRC include cytotoxic chemotherapy combined with inhibitors of VEGF or immune checkpoint inhibitors in patients with MSI-H tumors. The impact of sequential treatment with anti-VEGF and anti-EGFR therapies in mCRC has been the subject of investigation in recent years. This post hoc analysis evaluated overall survival (OS) by prior bevacizumab treatment in patients with BRAF V600E-mutant mCRC treated with the triplet, doublet, or control regimens in the BEACON CRC study. Of 665 patients enrolled in the study, the number of patients in the triplet, doublet, and control arms who received prior bevacizumab were 136 (61%), 140 (64%), and 122 (55%), respectively. For patients in the triplet arm, median OS (95% confidence interval [CI]) for those who had no prior bevacizumab treatment, bevacizumab treatment < 4 months before study treatment, or bevacizumab treatment ≥ 4 months before study treatment was 12.6 months (9.3–17.8; n = 88), 8.1 months (7.2–9.6; n = 103), and 7.9 months (6.3–not reached; n = 33), respectively. In the doublet arm, median OS (95% CI) for the same categories was 9.4 months (7.6–16.5; n = 80), 8.3 months (6.2–11.2; n = 111), and 10.7 months (7.5–17.7; n = 29), respectively. In the control arm, median OS (95% CI) for the same categories was 7.4 months (5.6–9.5; n = 99), 5.1 months (4.0–6.4; n = 103), and 4.4 months (2.0–11.6; n = 19), respectively. Median OS using a 6-month prior bevacizumab cut-off was similar to that for the 4-month cut-off. Additional analyses exploring the potential impact of prior bevacizumab use on encorafenib plus cetuximab with or without binimetinib treatment will be presented. This exploratory post hoc analysis evaluates OS in patients from BEACON CRC treated with encorafenib plus cetuximab with or without binimetinib to investigate the potential effects of prior bevacizumab treatment on subsequent regimens for patients with BRAF V600E-mutant mCRC. Reference: 1. Tabernero J, et al. J Clin Oncol. 2021;39(4):273–284.