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Vemurafenib and cobimetinib in BRAF-mutated melanoma
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Vemurafenib interrupts the BRAF/ MEK/ERK pathway in melanomas that harbour the BRAF V600E mutation (present in about 50% of patients). The addition of cobimetinib, a MEK inhibitor, to vemurafenib might prevent or delay the onset of resistance. In a previous open-label, phase 1b trial, 66 vemurafenib-refractory patients and 63 BRAF-inhibitor-naive patients with BRAF V600 mutation-positive metastatic melanoma were treated with the combination vemurafanib and cobimetinib. In treatment-naive patients, median progression-free survival was 13·7 months, 87% of patients had an overall response, and 10% a complete response. An additional 10% of patients had stable disease. In a phase 3 trial, James Larkin and colleagues randomly assigned 495 patients with previously untreated, unresectable, locally advanced or
metastatic BRAF V600E mutationpositive melanoma to receive vemurafenib and cobimetinib (n=247) or vemurafenib and placebo (n=248). Progression-free survival was the primary endpoint and in the combination group was 9·9 months, compared with 6·2 months in the placebo group (hazard ratio 0·51, 95% CI 0·39–0·68; p<0·001). 68% of patients in the combination group had an objective response, compared with 45% in the placebo group (p<0·001), with complete responses seen in 10% and 4% of patients, respectively. There was a non-significant increase in grade 3 or higher toxic effects in the combination group compared with the placebo group (65% vs 59%), but a decreased number of cutaneous cancers. Ruth Plummer (Northern Institute for Cancer Research, Newcastle, UK) notes: “The data reported are very
encouraging, with the combination treatment giving prolonged progression-free survival for patients. The combination of a BRAF and MEK inhibitor offers better outcomes without a significant increase in sideeffects and is another step forwards in treatment of patients with metastatic melanoma.” Christian Ottensmeier (University of Southmapton, Southampton, UK) adds: “We have seen a rapid development in the treatments for patients with BRAF-mutant melanoma and it is great news for our patients that the vemurafenib and cobimetinib combination leads to such clear clinical benefit. This is an exciting confirmation that targeting both the BRAF and MEK pathways is a potent treatment strategy for advanced melanoma.”
CNRI/Science Photo Library
Vemurafenib and cobimetinib in BRAF-mutated melanoma
Published Online October 10, 2014 http://dx.doi.org/10.1016/ S1470-2045(14)71023-X For the phase 1b trial see Articles Lancet Oncol 2014; 15: 954–65 For the study by Larkin and colleagues see N Engl J Med 2014; published online Sept 29. DOI:10.1056/NEJMoa1408868
Ahmadur Rahman
Thoracoscopic lobectomy versus thoracotomy for NSCLC Subroto Paul and colleagues used highquality observational data from the US Surveillance Epidemiology and End Results–Medicare database to compare the long-term survival (median followup 40 months) of patients with nonsmall-cell lung cancer after different lobectomy procedures. From 2007 to 2009, the investigators identified 6008 patients who were undergoing thoracoscopic lobectomy (n=1293; mean age 74·9 years [SD 5·8]) or thoracotomy lobectomy (n=4715; 74·2 years [5·7]). In a propensity-matched analysis, the differences in long-term survival between patients who had undergone thoracoscopic lobectomy versus those who had undergone thoracotomy lobectomy (1195 individuals in each group) were not significant: 3-year overall survival was 70·6% versus 68·1%, (p=0·55), 3-year cancer-specific survival was 92% versus 89·5% (p=0·05), and 3-year disease-free survival was
86·2% versus 85·4% (p=0·46). More patients in the thoracoscopic group than in the thoracotomy group had at least 12 nodes resected (37% vs 29%; p<0·0001). Luca Bertolaccini (Sacro Cuore Research Hospital, Negrar, Italy) notes, that “lobectomy is the procedure of reference for the treatment of lung cancer and the conventional approach is open or thoracotomic”. He says that Paul and colleagues’ study is interesting and the largest so far of “video-assisted thoracoscopic surgery (VATS) lobectomy practice in the USA”. Bertolaccini also notes that the investigators “found that patients who underwent VATS lobectomy had a more accurate lymph node dissection, not only because VATS is performed by experienced thoracic surgeons, but also because VATS magnifies the vision of the surgical field with a better approach to nodal stations”.
www.thelancet.com/oncology Vol 15 November 2014
According to Jianxing He (First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China), the investigators’ results lend “support to and substantially advance the previous analysis of several institutional case series and an examination of the Danish lung cancer registry, as well as our previous Chinese multi-institutional study”. Logistical challenges and a “lack of equipoise among the thoracic community have thus far prevented a large randomised controlled trial from being conducted”, He notes. “Given the current success and superior surgical outcomes, the future for VATS is bright. The emphasis is no longer on the issue of VATS versus open thoracotomy, but has shifted towards further refinement of this surgical technique and its use in complex resections.”
Published Online October 10, 2014 http://dx.doi.org/10.1016/ S1470-2045(14)71024-1 For the study by Paul and colleagues see BMJ 2014; published online Oct 2. DOI:10.1136/bmj.g5575
Farhat Yaqub e535
Vemurafenib interrupts the BRAF/ MEK/ERK pathway in melanomas that harbour the BRAF V600E mutation (present in about 50% of patients). The addition of cobimetinib, a MEK inhibitor, to vemurafenib might prevent or delay the onset of resistance. In a previous open-label, phase 1b trial, 66 vemurafenib-refractory patients and 63 BRAF-inhibitor-naive patients with BRAF V600 mutation-positive metastatic melanoma were treated with the combination vemurafanib and cobimetinib. In treatment-naive patients, median progression-free survival was 13·7 months, 87% of patients had an overall response, and 10% a complete response. An additional 10% of patients had stable disease. In a phase 3 trial, James Larkin and colleagues randomly assigned 495 patients with previously untreated, unresectable, locally advanced or
metastatic BRAF V600E mutationpositive melanoma to receive vemurafenib and cobimetinib (n=247) or vemurafenib and placebo (n=248). Progression-free survival was the primary endpoint and in the combination group was 9·9 months, compared with 6·2 months in the placebo group (hazard ratio 0·51, 95% CI 0·39–0·68; p<0·001). 68% of patients in the combination group had an objective response, compared with 45% in the placebo group (p<0·001), with complete responses seen in 10% and 4% of patients, respectively. There was a non-significant increase in grade 3 or higher toxic effects in the combination group compared with the placebo group (65% vs 59%), but a decreased number of cutaneous cancers. Ruth Plummer (Northern Institute for Cancer Research, Newcastle, UK) notes: “The data reported are very
encouraging, with the combination treatment giving prolonged progression-free survival for patients. The combination of a BRAF and MEK inhibitor offers better outcomes without a significant increase in sideeffects and is another step forwards in treatment of patients with metastatic melanoma.” Christian Ottensmeier (University of Southmapton, Southampton, UK) adds: “We have seen a rapid development in the treatments for patients with BRAF-mutant melanoma and it is great news for our patients that the vemurafenib and cobimetinib combination leads to such clear clinical benefit. This is an exciting confirmation that targeting both the BRAF and MEK pathways is a potent treatment strategy for advanced melanoma.”
CNRI/Science Photo Library
Vemurafenib and cobimetinib in BRAF-mutated melanoma
Published Online October 10, 2014 http://dx.doi.org/10.1016/ S1470-2045(14)71023-X For the phase 1b trial see Articles Lancet Oncol 2014; 15: 954–65 For the study by Larkin and colleagues see N Engl J Med 2014; published online Sept 29. DOI:10.1056/NEJMoa1408868
Ahmadur Rahman
Thoracoscopic lobectomy versus thoracotomy for NSCLC Subroto Paul and colleagues used highquality observational data from the US Surveillance Epidemiology and End Results–Medicare database to compare the long-term survival (median followup 40 months) of patients with nonsmall-cell lung cancer after different lobectomy procedures. From 2007 to 2009, the investigators identified 6008 patients who were undergoing thoracoscopic lobectomy (n=1293; mean age 74·9 years [SD 5·8]) or thoracotomy lobectomy (n=4715; 74·2 years [5·7]). In a propensity-matched analysis, the differences in long-term survival between patients who had undergone thoracoscopic lobectomy versus those who had undergone thoracotomy lobectomy (1195 individuals in each group) were not significant: 3-year overall survival was 70·6% versus 68·1%, (p=0·55), 3-year cancer-specific survival was 92% versus 89·5% (p=0·05), and 3-year disease-free survival was
86·2% versus 85·4% (p=0·46). More patients in the thoracoscopic group than in the thoracotomy group had at least 12 nodes resected (37% vs 29%; p<0·0001). Luca Bertolaccini (Sacro Cuore Research Hospital, Negrar, Italy) notes, that “lobectomy is the procedure of reference for the treatment of lung cancer and the conventional approach is open or thoracotomic”. He says that Paul and colleagues’ study is interesting and the largest so far of “video-assisted thoracoscopic surgery (VATS) lobectomy practice in the USA”. Bertolaccini also notes that the investigators “found that patients who underwent VATS lobectomy had a more accurate lymph node dissection, not only because VATS is performed by experienced thoracic surgeons, but also because VATS magnifies the vision of the surgical field with a better approach to nodal stations”.
www.thelancet.com/oncology Vol 15 November 2014
According to Jianxing He (First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China), the investigators’ results lend “support to and substantially advance the previous analysis of several institutional case series and an examination of the Danish lung cancer registry, as well as our previous Chinese multi-institutional study”. Logistical challenges and a “lack of equipoise among the thoracic community have thus far prevented a large randomised controlled trial from being conducted”, He notes. “Given the current success and superior surgical outcomes, the future for VATS is bright. The emphasis is no longer on the issue of VATS versus open thoracotomy, but has shifted towards further refinement of this surgical technique and its use in complex resections.”
Published Online October 10, 2014 http://dx.doi.org/10.1016/ S1470-2045(14)71024-1 For the study by Paul and colleagues see BMJ 2014; published online Oct 2. DOI:10.1136/bmj.g5575
Farhat Yaqub e535