BRAF mutations occur in 15% of colorectal patients. There are no targeted drugs approved by the FDA so far, and the prognosis is poor. Among them, BRAF V600E is the most common mutation.
Recently, the results of the Phase III BEACON CRC trial study announced: three-drug combination therapy of patients with metastatic colorectal cancer (CRC) who had previously received second-line treatment of BRAF V600E mutation-encorafenib (Bratovi) + binimetinib (Mektovi) + cetuxima Monoclonal antibody (erbital), compared with the combination of irinotecan and cetuximab, can reduce the risk of death by 48%.
Rezultati studije faze III pokazali su da je medijan ukupnog preživljavanja (OS) trostruke terapije bio 9.0 mjeseci, u usporedbi s 5.4 mjeseca kod pacijenata koji su primali cetuksimab i irinotekan.
Array BioPharma, the manufacturer of enkorafenib and binimetinib, said in a press release that it intends to submit these data for marketing approval in the second half of 2019.
Glavni istražitelj MD Anderson Centra za rak dr. Scott Kopetz rekao je da je ispitivanje BEACON CRC prvo kliničko ispitivanje faze III kod pacijenata s kolorektalnim bolesnicima s BRAF V600E-mutiranim tipom. Ima značajno poboljšanje u odnosu na standardnu kombinaciju tri lijeka i očekuje se da će promijeniti trenutni postojeći plan kliničkog liječenja.
Ostale identifikacije dobivene trostrukom terapijom
The US FDA previously granted the three-drug combination plan as a breakthrough treatment designation for the treatment of patients with BRAF V600E mutant metastatic Rak debelog crijeva, which was used after failure of first-line or second-line treatment. This decision is based on the results of the safety introduction phase of the BEACON CRC trial (a trial to assess the safety of drugs).
In March 2019, the National Comprehensive Cancer Network (NCCN) updated the clinical practice guidelines for colorectal cancer oncology, combining encorafenib + binimetinib + EGFR monoclonal antibody (cetuximab) as a BRAF V600E mutant metastatic colorectal cancer patient. Type 2A treatment is recommended and should be used after 1 or 2 lines of treatment have failed.
Tijekom faze sigurnog uvođenja, 30 bolesnika dobivalo je trostruku terapiju, 300 mg enkorafeniba jednom dnevno; 45 mg binimetiniba dva puta dnevno; a zatim kombinirana sa standardnom dozom cetuksimaba.
29 pacijenata ima BRAF V600 mutaciju, a 1% pacijenata ima mikrosatelitsku nestabilnost-visok status. Rezultati pokazuju da je trostruka shema ranije pokazala dobru toleranciju. Prema podacima pruženim na Simpoziju karcinoma probavnog trakta 2019., medijan vremena praćenja bio je 18.2 mjeseca, a rezultati su pokazali procijenjeni srednji opstanak bez napredovanja od 8.0 mjeseci i medijan ukupnog preživljenja od 15.3 mjeseca (godinu dana više). Uz lokalnu procjenu stope odgovora od 48%, 3 pacijenta postigla su potpuni odgovor.
Što se tiče sigurnosti, i triplet i duplex sheme dobro se podnose i nema slučajne toksičnosti. Dvije sigurnosne značajke također su u skladu s onima viđenim u svakoj od prethodnih studija.
This heavy study data may become the first targeted treatment plan for patients with metastatic colorectal cancer that does not contain chemotherapy drugs. This is undoubtedly an important good news for the population of patients with BRAF V600E mutant colorectal cancer who have a very high demand for effective treatment.
