Therefore, the dacomitinib dose was reduced to enable dose escalation of PD-0325901, as we hypothesised that robust MEK inhibition was necessary to block the KRAS-activated MAPK pathway before tumour cells activate their escape mechanism through upstream tyrosine kinase receptors.7 Because ocular toxicity, i.e. asymptomatic central serous retinopathy, emerged at the 5 and 6mg dose levels, we halted dose escalation at 6 mg, and established the RP2D with continuous dacomitinib dosing at 15 mg of dacomitinib QD plus 6 mg of PD-0325901 BID 21 days on/7 days off. The gene discussed is NTRK1; the disease is central serous retinopathy.