Afatinib, Osimertinib Sequence Shows Promise for EGFR-Positive NSLC

The GioTag study demonstrated that sequential afatinib and osimertinib improved overall survival among patients from the US with epidermal growth factor receptor mutation-positive non-small cell lung cancer and a T790M resistance mutation.

A new analysis from the GioTag study showed that sequential afatinib (Gilotrif) and osimertinib (Tagrisso) contributed to a median overall survival (OS) of almost 4 years among patients from the US with EGFR mutation-positive non-small cell lung cancer (NSCLC) and a T790M resistance mutation, according to Boehringer Ingelheim, the developer of afatinib.1

These findings are consistent with the global primary analysis of the GioTag study, as well as a separate, interim analysis conducted in the US.

“Developing resistance to EGFR [tyrosine kinase inhibitors; TKIs] is, unfortunately, an expected outcome for many people with this specific lung cancer, and strategies for sequencing treatments continue to evolve with the use of TKIs in clinical practice,” Balazs Halmos, MD, chief of thoracic and head and neck oncology at Montefiore Medical Center, said in a press release. “These real-world data provide further insight into the overall survival associated with afatinib and subsequent osimertinib treatment and reinforce that previous findings may have application in the US treatment setting for patients with T790M acquired resistance.”

The real-world retrospective, observational GioTag study is assessing the impact of first-line treatment with afatinib followed by osimertinib in patients with Del19/L858R EGFR mutation-positive NSCLC with acquired T790M mutations. In particular, this analysis looked at outcomes from a subgroup of 129 patients sourced from chart review and electronic records of consecutive patients treated at US treatment centers between December 28, 2017 and May 31, 2018.

Overall, the afatinib-osimertinib sequence was associated with a combined median time on treatment (time to treatment failure; TTF) of 28.4 months.2 A similar TTF was also observed across several subgroups, including those with EGFR Del19-positive disease (30.3 months), those with an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1 (32.7 months), and in patients 65 years of age or older (34.1 months).

In the most recent analysis, median time on afatinib was 11.3 months (90% CI: 10.3-12.0) and 15 months (90% CI, 13.4–16.4) for osimertinib. Moreover, median overall survival was 47.6 months (90% CI, 35.5-51.5). Results from the final analysis for the full GioTag patient population are expected to be published later this quarter.

“These real-world data offer additional evidence that afatinib prior to osimertinib may be an important consideration for patients with EGFR mutation-positive non-small cell lung cancer,” Bjoern Rueter, MD, head of the Oncology Therapeutic Area in the Boehringer Ingelheim US branch, said in the release. “Cancer can take away so much, and understanding strategies such as treatment sequencing is one way Boehringer Ingelheim is taking cancer on.”


1. Additional analysis of real-world data confirms sequential Gilotrif® followed by osimertinib provided a median overall survival of nearly four years in U.S.-treated patients with EGFR mutation-positive NSCLC [news release]. Ridgefield, Connecticut. Published August 10, 2020. Accessed August 10, 2020.

2. Feinberg B, Halmos B, Gucalp R, Tang W, Moehring B, Hochmair MJ. Making the case for EGFR TKI sequencing in EGFR mutation-positive NSCLC: a GioTag study US patient analysis. Future Oncology. Published online August 6, 2020. doi:10.2217/fon-2020-0188