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The study included 583 participants who received vemurafenib monotherapy and 247 who received vemurafenib plus cobimetinib. Adverse events requiring vemurafenib\/cobimetinib dose adjustment within the first 28\u00a0days of therapy were significantly associated with OS (hazard ratio (HR) [95% CI]: dose reduced\/interrupted\u00a0=\u00a00.79 [0.65\u20130.96]; drug withdrawn\u00a0=\u00a01.18 [0.71\u20131.96]; <jats:italic>p<\/jats:italic>\u00a0=\u00a00.032), PFS (HR [95% CI]: dose reduced\/interrupted\u00a0=\u00a00.82 [0.67\u20130.99]; drug withdrawn\u00a0=\u00a01.58 [0.97\u20132.58]; <jats:italic>p<\/jats:italic>\u00a0=\u00a00.017) and objective response (odds ratio (OR) [95% CI]: dose reduced\/interrupted\u00a0=\u00a01.35 [0.99\u20131.85]; drug withdrawn\u00a0=\u00a00.17 [0.06\u20130.43]; <jats:italic>p<\/jats:italic>\u00a0=\u00a0&lt;0.001). Arthralgia occurring within the first 28\u00a0days of vemurafenib or vemurafenib plus cobimetinib therapy was also significantly associated with favourable OS (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.026), PFS (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.042) and objective response (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.047).<\/jats:p>","DOI":"10.1111\/pcmr.12773","type":"journal-article","created":{"date-parts":[[2019,2,13]],"date-time":"2019-02-13T18:35:32Z","timestamp":1550082932000},"page":"576-583","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Effect of early adverse events on response and survival outcomes of advanced melanoma patients treated with vemurafenib or vemurafenib plus cobimetinib: A pooled analysis of clinical trial data"],"prefix":"10.1111","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7652-4378","authenticated-orcid":false,"given":"Ashley M.","family":"Hopkins","sequence":"first","affiliation":[{"name":"Flinders Centre for Innovation in Cancer &amp; 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