A phase II study of daily encorafenib in combination with biweekly cetuximab in patients with BRAF V600E mutated metastatic colorectal cancer: the NEW BEACON study.

BACKGROUND: Patients with BRAF V600E mutated metastatic colorectal cancer (mCRC) have a poor prognosis. The introduction of BRAF targeted therapy with encorafenib and weekly administered cetuximab have shown improved survival with a median progression free survival (PFS) of 4.3 months. However, a regimen with cetuximab given every second week may have comparable efficacy and is more convenient for patients. While BRAF targeted therapy is a new standard therapy in pre-treated patients with BRAF V600E mutated mCRC, resistance invariably occurs and is an emerging challenge. The aim of this study is to investigate the efficacy and tolerability of cetuximab given every second week in combination with daily encorafenib and to explore the correlation between markers of resistance and outcome. METHODS: The study is an open label, single arm, phase II study, investigating the efficacy and tolerability of cetuximab given every second week in combination with encorafenib in patients with BRAF V600E mutated mCRC. Furthermore, we will be investigating mechanisms of response and resistance against BRAF targeted therapy though comprehensive genomic profiling on tumor tissue and blood for circulating tumor DNA analysis. A total of 53 patients (19 + 34 in two steps) will be included according to Simon's optimal two stage design. The primary end point of the study is 2 months PFS rate. DISCUSSION: By combining BRAF inhibitor with cetuximab given every second week we can halve the number of visits in the hospital compared to the currently approved regimen with weekly cetuximab. This seems particularly relevant in a group of patients with a median overall survival of 9.3 months. Resistance after initial response to targeted therapy can be either adaptive (e.g., epigenetic, or transcriptomic alterations) or acquired (selective genetic alterations - e.g., activating de novo mutations) resistance. It is of great importance to untangle these complex mechanisms of resistance in patients with BRAF V600E mutated mCRC to improve treatment strategies in the future potentially even further. TRIAL REGISTRATION: EU Clinical Trial Register, Eudract no. 2020-003283-10 . Registered on 11 November 2020.

Municipality-based pragmatic rehabilitation stratified in accordance with individual needs-results from a longitudinal survey study.

OBJECTIVE: Evidence on municipality-based cancer rehabilitation is sparse. This longitudinal study explores the following: (1) Rehabilitation needs, (2) effectiveness of municipality-based rehabilitation, and (3) whether rehabilitative services are stratified according to individual needs in breast cancer patients. METHODS: We collected data from a longitudinal survey among 82 breast cancer patients referred to municipality-based rehabilitation at the Copenhagen Centre for Cancer and Health. Rehabilitation needs, health-related quality of life (HRQoL), and functional status were collected using patient-reported outcomes (PROs) including distress thermometer, problem list, Functional Assessment of Cancer Therapy-Breast questionnaire (FACT-B), and upper body function with the abbreviated disability of the arm, shoulder, and hand (Quick-DASH) questionnaire. Data collection time points are as follows: entry, follow-up, and end of intervention. RESULTS: At referral, scores were (mean (range)) distress 4.0 (0-10), problems 9.5 (0-24), and FACT-B 103.0 (49.8-135.5). HRQoL increased during rehabilitation (FACT-B ∆ mean 8.1 points (> MID, p < 0.0001)); 56% had a positive change, 34% no difference, and 11% a decline. Those with the lowest FACT-B entry score had significantly longer duration of rehabilitation (10.9 vs 8.7 months, p < 0.001), higher number of services (7.0 vs 5.3, p < 0.003), and participated more in group-based exercise (+3 sessions: 57% vs 8%, p < 0.001). CONCLUSION: This is the first study to report on pragmatic municipality-based cancer rehabilitation. The results suggest that services are aimed at patients with rehabilitation needs, improve HRQoL, and are properly stratified to those who need it the most. We suggest future monitoring of municipality-based rehabilitation services to ensure quality of care.

[Essex-Lopresti lesion is often undiagnosed].

In this review, the diagnostics of the Essex-Lopresti lesion is discussed. The lesion is a combination of fracture of the head of radius, rupture of the interosseous mebrane (IOM) and dislocation of the distal radioulnar joint. The lesion is often overlooked in the primary clinical settings, and it is correlated to severe instability, osteoarthritis and pain if untreated. The tools for diagnosing the condition are physical examination of relevant anatomical structures, radiographs of elbow and wrist and ultrasonic evaluation of IOM as well as peroperative tests of stability. The treatment is primarily focused on re-establishing stability of IOM.