c-met inhibitors Within 2 weeks of starting afatinib (50 mg/day), the patient had a rapid clinical and symptomatic response, with disappearance of all disease-related symptoms, as well as overall SD with a radiological response in liver and pleura, which was maintained for 3 months . Treatment with afatinib (50 mg/day) was associated with skin-related AEs, diarrhea and mucosal inflammation with intermittent epistaxis, aphthous stomatitis and dry eyes. The time to progression on single-agent afatinib was 4 months; following PD in
KU-0063794 October 2008, the patient received afatinib (40 mg/day) combined with weekly paclitaxel (80 mg/m2). After one cycle, disease-related symptoms disappeared and a dramatic partial remission was seen. As of July 2009, this patient had an ECOG PS of 0, a disease volume of less than that at her remission after first-line c-met inhibitor drug cisplatin-based chemotherapy 2.5 years earlier . Sustained control of carcinoembryonic antigen (CEA) tumor marker levels was also achieved during afatinib treatment. There was an increase in CEA levels during ineffective prior chemotherapy treatment and CEA levels declined rapidly to normal after combination of afatinib and weekly paclitaxel. Afatinib treatment was continued for a total of 15 months, 11 of which were in combination with paclitaxel,
c-met pathway inhibitor after which time the patient developed a brain metastasis without concurrent progression at the other disease sites. Adverse events with afatinib and weekly paclitaxel were mild and included skin reaction, diarrhea, fatigue and hematological AEs. After going off study in September 2009, the patient received trastuzumab sequentially combined with weekly paclitaxel for 6 months (CEA marker stabilization for 3 months), liposomal doxorubicin for 4 months (marker stabilization for 2 months), weekly cisplatin for three administrations, and oral etoposide for 3 months with no further clinical benefit.
In addition, she developed leptomeningeal disease in June 2010, which was treated with four intrathecal administrations of depocyte leading to a durable complete cytological and symptomatic response of her leptomeningeal disease. The patient died in March 2011, with an overall survival of 32 months after inclusion in the study.