Afatinib Activities Different in Uncommon EGFR Mutations in Advanced Non-Small Cell Lung Cancer

Yi-Long Wu, MD Professor
Vice president, Guangzhou People's Hospital
Guangdong Academy of Medical Science
President, Guangzhou Lung Cancer Research Institute
Photo: Oncology Frontier(肿瘤瞭望)

Yi-long Wu, MD Prof, Guangzhou People's Hospital,  Guangdong Academy of Medical Science, the corresponding author, participated  in a paper published in The Lancet Oncology, June 3, 2015 (DOI: http://dx.doi.org/10. 1016/S1470-2045 (15)00026-1) regarding Afabinib's activities in rare EGFR mutations in advanced Lung Adenocarcinomas.

Conclusions

After post hoc analysis of 3 clinical trials, LUX-lung 2(NCT00525148), LUX-Lung 3(NCT00949650) and LUX lung 6(NCT01121393), in Tyrosine kinase  inhibitor naive patients, treated with Afatinib, Yang etc. by categorized all uncommon EGFR mutations into 3 groups, found that Afatinib worked differently from each group.

Afatinib worked better in point mutations or duplication in exons 18-21, Gly719Xaa, Leu861Gln, Ser768lle, benefit less in patients with de-novo Thr790Met and exon 20 insertion mutations.

Design 

The  3 groups were: group 1 with point mutations or duplication in exons 18–21; group 2 with de-novo Thr790Met mutations in exon 20 alone or in combination with other mutations; group 3 with  exon 20 insertions.

Most uncommon EGFR mutations Gly719Xaa, Leu861Gln, and Ser768Ile, alone or in combination with other mutations were analyzed as well.

Results in details

	Objective responses	Median progression-free survival	Median overall survival
Group 1	71·1%, 95% CI 54·1–84·6	10·7 months (95% CI 5·6–14·7)	19·4 months (95% CI 16·4–26·9)
Group 2	14·3%, 1·8–42·8	2·9 months (1·2–8·3)	14·9 months (8·1–24·9)
Group 3	8·7%, 1·1–28·0	2·7 months (1·8–4·2)	9·2 months (4·1–14·2)
Gly719Xaa	77·8%, 95% CI 52·4–93·6
Leu861Gln	56·3%, 29·9–80·2
Ser768Ile	100·0%, 63·1–100·0

Interpretation

Although uncommon EGFR in non small cell lung cancer is rare, only accounts 10%, but by pinpointing the certain types, it will guide clinical decisions more effectively.

Note

James C-H Yang, MD, of National Taiwan University, and Lecia V. Sequist, MD, of Massachusetts General Hospital Cancer Center, contributed equally to this article.
This study was funded by Boehringer Ingelheim.

Reference:

Yang JCH, Sequist LV, Geater SL, et al. (2015). Clinical activity of afatinib in patients with advanced non-small-cell lung cancer harbouring uncommon EGFR mutations: a combined post-hoc analysis of LUX-Lung 2, LUX-Lung 3, and LUX-Lung 6. The Lancet Oncology.