Afatinib (Gilotrif) Efficacious in the EGFR+ NSCLC With Uncommon Mutations, Regardless of Ethnicity

According to outcomes from a pooled analysis cane during the 2020 IASLC North America Conference on Lung Cancer, afatinib was found to be effective when used in Asian and non Asian patients with NSCLC with the major uncommon as well as compound EGFR mutations, irrespective of ethnicity. 

The outcomes from a pooled analysis of the randomized clinical trials and real-world findings showed that afatinib elicited ORR of 66 percent in Asian patients with the EGFR mutated NSCLC vs 59 percent in the non-Asian patients. 

Besides in Asian patients, the median DOR (Duration of Response) was noted as 14.7 months in comparison with the 15.9 months in the non Asian patients.

The objective response rate with afatinib in Asian patients whose tumors harbored a G719X mutation was noted as 62 percent vs 65 percent in non Asian patients.

For a population with a L861Q mutation, the objective response rate was noted as 60 percent vs 50 percent, respectively. Lastly, in those with a S768I mutation, the objective response rate was noted as 80 percent vs 25 percent, respectively.

According to Bjoern Rueter, MD, therapeutic head of oncology, USA, at Boehringer Ingelheim, “These findings sets further expand our understanding of afatinib’s therapeutic profile in the metastatic non-small cell lung cancer among population with EGFR mutation +Ve disease.” 

“As we continue to take cancer on at Boehringer Ingelheim, our ongoing study is aimed at the supporting unmet treatment requirements for the lung cancer and broader oncology community through leading science,” Bjoern Rueter added. 

According to the study authors, The EGFR mutations which are not common are known to show heterogeneity with regard to their sensitivity to the EGFR TKIs.

Afatinib (Gilotrif) has previously showcased wide activity against the uncommon mutations in vitro, together with the encouraging clinical efficacy with regard to the mutations L861Q, S768I and G719X. 

In spite of this early promise, the efficacy of the inhibitory activity of afatinib (Gilotrif) against the other uncommon epidermal growth factor receptor mutations is limited.

For the pooled analysis, researchers assessed the activity of afatinib (Gilotrif) in Asian as well as non Asian patients with non-small cell lung cancer and uncommon epidermal growth factor receptor mutations who were not taken prior treatment with the EGFR TKIs; these patients had taken treatment in randomized controlled trials or in the real world findings. 

Mutations who are not common included de novo T790M; exon-20 insertions; major mutations who are not common like L861Q, G719X, and S768I; compound mutations; and certain other uncommon alterations.

The respective key end points of the analysis included ORR, DOR, and time to the failure of treatment. 

Of the Asian (n = 178) and non Asian (n = 120) patients with the uncommon mutations considered in the analysis, 62 percent and 35 percent, respectively, had a major uncommon mutation.

Twenty percent and 20 percent, respectively, had G719X only; 26 percent and 8 percent, respectively, had L861Q only; 3 percent and 4 percent, respectively, had S768I only; and 16 percent and 39 percent, respectively, had exon-20 insertions.

The additional outcomes exposed that the objective response rate in Asian patients with the compound mutations was 81 percent vs 100 percent in the non Asian patients.

The median DOR in the Asian and non Asian patients with these mutations was noted as 11.5 months and 18.6 months, respectively.

The Asian patients with the other uncommon mutations have an objective response rate of 79 percent vs 60 percent in the non Asian patients.

Within this subpopulation, the median DOR in the Asian and non Asian patients was noted as 9.0 months vs 10.7 months, respectively.

Else, certain patients who harbored exon-20 insertions responded to the afatinib. The objective response rate in Asian patients who harbored these mutations was noted as 21 percent vs 23 percent in the non Asian patients.

Notably, the time to failure of treatment proved to be longest in patients with the non small cell lung cancer that harbored major uncommon and compound epidermal growth factor receptor mutations.

Authors concluded in the abstract, “Afatinib had the wide activity against the other uncommon epidermal growth factor receptor mutations and certain exon-20 insertion mutations, unaffected by the ethnicity.” 

 “The Asian patients appeared to have a healthy proportion of the major uncommon mutations, known to be highly sensitive to the afatinib,” authors added. 

Reference:

https://www.onclive.com/view/afatinib-efficacious-in-egfr-nsclc-harboring-major-uncommon-mutations-irrespective-of-ethnicity

https://www.oncnursingnews.com/view/afatinib-efficacious-in-egfr-nsclc-with-uncommon-mutations-regardless-of-ethnicity