Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), gefitinib or erlotinib, is a key drug in patiens with EGFR-mt NSCLC. Its efficacy would be predicted by development of skin rash. However, although afatinib, 2nd generation EGFR-TKI, has proved to be effective, it has not been fully evaluated if the occurrence of any toxicity is a potential surrogate for its efficacy. Now, we investigated a potential association between development of toxicity and efficacy of afatinib.
We retrospectively studied consecutive 49 patients with EGFR-mutant NSCLC who received afatinib therapy between 2009 and 2015. Relationship with several toxicities and tumor response was examined. To avoid the potential bias of early treatment failure, we excluded pts who failed to continue afatinib for more than 1week.
The Grade 2 or worse common adverse events (AEs) included skin rash in 17 patients (35%), diarrhea in 19 (39%) and mucositis in 15 (31%). Of these, number of patients who developed ≥ Grade 2 AEs within the first week was 5 (10%; skin rash), 12 (25%; diarrhea) and 4 (8%; mucositis). As for objective response, 21 (43%) of the 49 had partial response. In association with AEs and antitumor effect, those who had Grade 2 or worse skin rash within the first week tended to have better tumor response as compared with those who did not have (80% vs. 39%; p = 0.077), (Table).
Relationship with early development of adverse events and response
|No. of patients Response (-)||No. of patients (%) Response (+)|
|≥ G2 hepatitis yes no||1 27||0 (0%) 21(44%)||0.382|
|≥ G2 skin rash yes no||1 27||4 (80%) 17 (39%)||0.077|
|≥ G2 diarrhea yes no||6 22||6 (50%) 15 (41%)||0.565|
|≥ G2 paronychia yes no||1 27||0 (0%) 21 (44%)||0.382|
|≥ G2 mucositis yes no||2 26||2 (50%) 19 (42%)||0.763|
|≥ G2 gastritis yes no||0 28||0 (0%) 21 (43%)|
|≥ G2 dysgeusia yes no||0 28||0 (%) 21 (43%)|
|≥ G2 ILD yes no||0 28||0 (0%) 21 (43%)|
We demonstrated that early development of skin rash would predict the response to afatinib monotherapy.
Clinical trial identification
K. Hotta: received honoraria from Eli Lilly Japan, Taiho Pharmaceutical, Chugai Pharmaceutical and Sanofi-Aventis. N. Nogami: received honoraria from AstraZeneca, Chugai Pharmaceutical, Taiho Pharmaceutical and Boehringer Ingelheim. N. Takigawa: received honoraria from Chugai Pharmaceutical, Taiho Pharmaceutical and Sanofi-Aventis. M. Tanimoto: received donated funds from Nihon Kayaku. K. Kiura: received honoraria from Eli Lilly Japan, Nihon Kayaku, AstraZeneca, Daiichi-Sankyo Pharmaceutical, Chugai Pharmaceutical, Taiho Pharmaceutical and Sanofi-Aventis; received research donated funds from Nihon Kayaku. All other authors have declared no conflicts of interest.