Advance reports 341

Advance reports We report the highlights of two recent meetings, the annual meeting of the European League Against Rheumatism (EULAR), 25–28 May 2011, London, and the annual meeting of the American Society of Clinical Oncology (ASCO), 3–7 June 2011, Chicago.

Dawn Powell GM Peter Sayer GM email [email protected]

EULAR patients with very early stage or collective clinical experience, and early stage rheumatoid arthritis who we continue to gain important Etanercept were treated with methotrexate and knowledge about these conditions Several studies on etanercept etanercept had a higher probability and the potential benefits of (Enbrel) were presented at the of achieving remission and one treating patients with certain EULAR congress. or no swollen joints after a year chronic inflammatory diseases.” The interim results of the than patients, at the same disease PRESERVE trial1 were the focus stages, treated with methotrexate References of one of these studies. These alone. Clinical remission with the results showed that a substantial combination of etanercept and 1. Poster THU0245, EULAR 2011 proportion of patients with methotrexate was achieved despite 2. Abstract AB0439, EULAR 2011 moderately active rheumatoid stricter criteria from EULAR 3. Poster THU0488. EULAR 2011 arthritis (RA) receiving a regarding the definition of clinical 4. PosterTHU0191. EULAR 2011 combination of etanercept and remission (achievement of no or Studies sponsored by Pfizer methotrexate for 36 months one swollen joints and a simplified achieved a normal health-related disease activity score). Certolizumab pegol quality of life score (57%), a Other studies presented Adding certolizumab pegol clinically meaningful improvement on etanercept at the EULAR (Cimzia) to current therapy for in fatigue (73%), and improved congress showed: that compared patients with rheumatoid arthritis sleep adequacy (56%). Investigators with sulfasalazine, it improved was associated with a rapid and Smolen et al concluded: “These functionality independently of its consistent clinical response in a outcomes indicate benefits that effects on mobility in patients with study presented at EULAR.1 The are consistent with prior studies ankylosing spondylitis;3 and that results were from the latest analysis in different populations (eg, it had greater effect on quality of of the REALISTIC study. more severe RA) as well as being life in patients with psoriasis and In the overall study population, consistent with clinical and psoriatic arthritis than in patients the ACR20 response rates at radiographic results from this with psoriasis alone.4 week 12 were statistically higher population.” They added that Regarding the data presented in the group of patients receiving further data from the PRESERVE at EULAR, the Senior Vice certolizumab than in those trial, from the second period of President of Clinical Development receiving placebo (51.1% versus the study, will indicate whether and Medical Affairs at Pfizer, 25.9%, respectively). Te response the initial responses observed who are the manufacturers of rate with certolizumab did not for patient-reported outcomes etanercept, said: “With its first significantly differ between patients are maintained after the dose of approval for RA in 1998 in the who had previously received TNF etanercept is removed or reduced. US and 2000 in Europe, Enbrel inhibitors and those who had not Another study2 showed that has 2.5 million patient-years of (47.2% and 53.5%, respectively).

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There also was no significant treatment arms. In a previous level five or above). Words used difference in response rates study, tocilizumab monotherapy to describe morning symptoms between those who were receiving was shown to have superiority included: sore (53%), tired certolizumab monotherapy over methotrexate in standard (56%), swollen (58%), restricted and those who were receiving rheumatoid arthritis parameters (56%), inflamed (45%), and concomitant disease-modifying at 24 weeks.2 The first and only frozen (19%). antirheumatic drugs (DMARs); biologic therapy to do so Overall, 83% of patients 47.6% and 52%, respectively. Other Professor Philip Conaghan, claimed that their symptoms benefits observed with certolizumab Professor of Musculoskeletal had a significant impact on included improvements in fatigue, Medicine at the University of Leeds, their quality of life. But in the sleep problems, and pain. said about the ACT-RAY results: UK, this figure rose to 92%. The Professor Roy Fleischmann, “This data is very promising for reduced quality of life associated from the University of Texas patients who are unable to tolerate with morning symptoms Southwestern Medical School, said: methotrexate and could provide affected patients’ emotional “These results are encouraging a more efficacious alternative to wellbeing. According to the because they demonstrate the current therapy.” survey, half of patients were clinical usefulness of certolizumab “frustrated” by their inability pegol in a broad population of References to do certain things because of patients with RA and reflect the their symptoms, more than a patient variability that we see in 1. Abstract OP0020 third felt that they were a burden everyday practice.” 2. Jones G, et al. Ann Rheum Dis 2010; to others, and almost a quarter 69 : 88–96 felt “depressed” about their References Trial sponsored by Roche symptoms. Nearly all (96%) of the 1. Poster FRI024, EULAR 2011 RA and QoL rheumatologists surveyed A research report, presented recognised that morning Trial sponsored by UCB at EULAR and published in symptoms had an impact on the Annals of the Rheumatic patients’ lives, but 62% did Tocilizumab Diseases, has revealed the impact not specifically treat these Tocilizumab (RoActemra) of RA on quality of life.1 symptoms. Only one fifth of monotherapy is as effective as The report surveyed patients said that their current tocilizumab in combination with rheumatologists and patients treatment was completely methotrexate in people with across 21 countries in Europe effective for relieving their rheumatoid arthritis, a study about the effect of morning morning symptoms and 66% presented at EULAR shows.1 stiffness and pain associated with of European rheumatologists The ACT-RAY study RA on quality of life. It found agreed that there was a need for randomised patients with that stiffness and pain in the new treatments that specifically moderate-to-severe rheumatoid morning was a daily occurrence address stiffness and pain in the arthritis who had an inadequate for six in 10 of the patients in morning. response to methotrexate to remain the survey (to be eligible for Professor Douglas Veale, on stable-dose methotrexate the survey, patients had to Professor of Medicine and plus 8 mg tocilizumab or 8 mg experience these symptoms Consultant Rheumatologist tocilizumab plus placebo. Afer 24 at least three times a week). at St Vincent’s University weeks, the DAS28 remission rates Three quarters of the patients Hospital, Dublin, said that for those receiving tocilizumab who had daily symptoms rated the report showed it was clear monotherapy was 35% and 40% for their symptoms as being at the that the morning stiffness and those receiving the combination (a higher end of the scale (asked pain associated with RA had non-significant difference). There to describe the severity of their an “emotional and economic” was also no significant difference symptoms on a scale of 0–10, impact on patients’ lives. “We in safety profiles between the two they said their symptoms were at need to ensure these symptoms

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are discussed with patients so that References patients receiving vemurafenib was any negative impact on their lives 84% compared with 64% of patients is addressed and minimised.” 1. Abstract AB0037. EULAR 2011 receiving darcarbazine.Tis equated to a 63% relative reduction in the References risk of death in patients receiving ASCO the new drug compared those 1. Understanding the impact of morning receiving dacarbazine. stiffness and pain due to rheumatoid Metastatic melanoma Progression-free survival was arthritis. A European Research Report As widely reported in the national also better in the vemurafenib in 21 countries press, a study simultaneously group. The estimated median Te surveys for the report were published in the New England progression-free survival was conducted by an independent Journal of Medicine and presented 5.3 months for patients taking research company and funded at ASCO shows that a new drug, vemurafenib and 1.6 months for by Mundipharma, who produce vemurafenib, has the potential to patients taking dacarbazine. This a treatment for RA (Lodotra) be the first significant treatment equated to a 74% relative risk that is particularly for those breakthrough for metastatic reduction in tumour progression who have morning stiffness. melanoma in 30 years.1 with vemurafenib. Furthermore, At present, patients with stage 48% of patients receiving Gout IV melanoma have a poor prognosis vemurafenib met the criteria for An abstract study indicated that and, depending on their substage, a confirmed response compared febuxostat (Adenuric) 80 mg is an only survive for eight to 18 months with only 5% of patients taking more effective antihyperuricemic after diagnosis. Dacarbazine, the dacarbazine (slightly lower than agent than the standard treatment standard chemotherapy used to reported in other studies). allopurinol. treat metastatic melanoma, is Investigators Chapman et al The study was a meta- associated with a 7–12% response explained that one of the reasons analysis of randomised rate and a median overall survival of for conducting the study was controlled trials comparing 5.6 to 7.8 months. that recent studies had raised the febuxostat with allopurinol About 40–60% of cutaneous possibility that melanomas with (found via the online medical melanomas are associated with the BRAF V600E mutation were database Pubmed). It found that mutations in the BRAF gene. more aggressive and less sensitive overall, febuxostat was superior Of these mutations, 90% relate to chemotherapy than BRAF wild- to allopurinol in achieving the to the BRAF V600E mutation. type melanomas. Tey concluded: target serum urate level (<6 mg/ Vemurafenib is a potent inhibitor “Our results show that single- dl), the primary outcome, of mutated BRAF and has agent vemurafenib improved at the end of the study. The been showed to have marked the rates of response and of both investigators concluded that antitumour effects against progression-free survival and febuxostat was equally safe melanoma cells lines with the overall survival, as compared as allopurinol but advised: BRAF V600E mutation but not with darcarbazine, in patients “Prophylaxis with colchicine is, against cells with wild-type BRAF. with metastatic melanoma with however, indicated at the start In the study, patients with BRAF V600E. These findings of the therapy due to slightly previously untreated, unresectable provide a solid foundation increased occurrence of gouty stage IIIC or IV melanoma and for the development of future flares before two months of who tested positive for the BRAF combination therapies.” therapy [with febuxostat]. V600E mutation were randomised One of the principal Febuxostat would be a better to receive vemurafenib (at 960 mg investigators of the study, Dr James choice in patients with mild-to- twice daily orally) or dacarbazine Larkin, from the Royal Marsden moderate renal insufficiency and (at 1000 mg per square metre of Hospital, said that “without for those who are intolerant to body-surface area by intravenous question”, the results represented allopurinol.” infusion every three weeks). Afer a major turning point in the six months, overall survival in treatment of metastatic melanoma.

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References However, this increase was not References statistically significant. 1. Chapman P, Hauschild A, Robert Mr Giles Toogood, Consultant 1. Abstract 4574. ASCO 2011 C, et al. Improved survival with Hepatobiliary Surgeon at St James’s vemurafenib in melanoma with BRAF Hospital in Leeds, said: “For most V600E mutation. N Eng J Med 2011; Study sponsored by Celgene Epub patients with advanced cancer, the chance to live longer, or even Renal cell carcinoma Trial supported by Roche be cured, are the most important Axitinib significantly extends benefits that treatments can offer.” progression free survival in Colorectal cancer He added that the results were patients with previously treated A new study, which was presented “extremely important” for both advanced renal cell carcinoma at ASCO, has found that adding patients with liver-limited disease compared with sorafenib, a new cetuximab (Erbitux) to standard and patients with non liver-limited study has shown.1 first-line chemotherapy improves disease. “We have a strong sign The study assessed 723 clinical outcome in patients that both groups can benefit from, patients with clear-cell advanced with KRAS wild-type metastatic cetuximab combination therapy.” renal cell carcinoma who had colorectal cancer who have liver- progressed following prior limited disease or who have non Trial sponsored by Merck therapy with regimens containing liver-limited disease. Serono sunitinib, cytokines, bevacizumab In patients with KRAS wild- or temsirolimus. Patients were type colorectal cancer, the liver is References randomised to receive axitinib (at an important area for investigation a starting dose of 5 mg twice daily) because resection of colorectcal liver 1. Abstract 3576. ASCO 2011 or sorafenib (400 mg twice daily). metastases is a potentially curative Prostate cancer Compared with patients receiving option. Tis new study reviewed the A combination of lenalidomide sorafenib, patients receiving treatments arms of the CRYSTAL (Revlimid), bevacizumab (Avastin), axitinib had a 43% improvement and OPUS studies (which both docetaxel, and prednisone was in median progression-free showed that adding cetuximab to associated with a high response rate survival. A principal investigator standard first-line chemotherapy in patients with metastatic castrate of the study, Dr Brian Rini, improved clinical benefit in patients resistant prostate cancer in an said that the data were useful with KRAS wild-type metastatic abstract presented at ASCO. because they helped doctors to colorectal cancer) according to Prednisone and docetaxel are advance their understanding metastatic site, resection rates, already established as effective of renal cell carcinoma, which and progression-free and overall treatments for metastatic prostate has limited proven treatment survival times. cancer. In a previous study, options when the patient Investigators found that the Huang et al hypothesised that has been previously treated. addition of cetuximab improved the addition of lenalidomide “The clinically meaningful outcome across clinical efficacy and bevacizumab could improve improvement in progression- endpoints in both patients with overall survival in this patient free survival seen with axitinib liver-limited disease and those population. Therefore, in this is even more encouraging as it with non liver-limited disease. For study, they investigated a cycle was accompanied by generally example in patients with non liver- of treatments involving all four manageable tolerability, an limited disease, the addition of therapies. They found that the important consideration for cetuximab increased overall survival combination was associated with these patients.” by more than five months compared an overall response rate of 86.4% with standard chemotherapy alone. and that all responding patients References Also, the rate of potentially curative had at least a 50% reduction in liver surgery increased by 2–3 fold prostate specific antigen (PSA). 1. Abstract 4503, ASCO 2011 with the addition of cetuximab in The results were achieved with patients with liver-limited disease. manageable toxicity. Trial sponsored by Pfizer

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