Sequential Afatinib and Osimertinib Shows Continued OS Benefit in EGFR+ NSCLC

Treatment with afatinib (Gilotrif) followed by osimertinib (Tagrisso) resulted in a median overall survival (OS) benefit of almost 4 years in US patients with EGFR T790M–positive non–small cell lung cancer (NSCLC) in the real-world setting, according to results from a new analysis from the phase 3 GioTag study (NCT03370770).¹

These data proved to be consistent to that of the global primary analysis of the trial and a separate, interim US analysis, according to Boehringer Ingelheim, the developer of afatinib.

“Developing resistance to EGFR 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/Head and Neck Oncology at Montefiore Medical Center, stated in a press release.² “These real-world data provide further insight into the OS 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.”

Results from this analysis showed that the median OS with afatinib followed by osimertinib was 47.6 months (90% CI, 35.5-51.5). Moreover, the Kaplan-Meier estimate of 2-year OS was 85% at a data maturity of 35%.

In 129 patients at centers throughout the United States, the overall median time-to-treatment failure (TTF) was 28.4 months (90% CI, 27.0-34.1). The median time on afatinib was 11.3 months (90% CI, 10.3-12.0) and 15.0 months with osimertinib (90% CI, 13.4-16.4). The median time between the end of afatinib treatment and the start of osimertinib treatment was 22 days.

When broken down by different subgroups based on patient baseline and disease characteristics, results showed a lengthy median TTF in patients with EGFR Del19-positive (n = 91) disease of 30.3 months (90% CI, 28.1–not reached [NR]), patients with an ECOG performance status of 0-1 (n = 100) of 32.7 months (90% CI, 28.4-NR), and patients aged 65 years and older (n = 38) of 34.1 months (90% CI, 19.9-44.5).

Encouraging median TTF was also reported in patients under 65 years of age (n = 91), at 28.4 months (90% CI, 27.0-32.7), and patients with an ECOG performance status of 2 or more (n = 28), at 22.6 months (90% CI, 16.0-27.6).

“These real-world data offer additional evidence that afatinib prior to osimertinib may be an important consideration for patients with EGFR mutation–positive NSCLC,” Bjoern Reuter, MD, Therapeutic Area Head Oncology at Boehringer Ingelheim, stated in the press release. “Cancer can take away so much and understanding strategies such as treatment sequencing is one way Boehringer Ingelheim is taking cancer on.”

Previously, updated interim results of the trial showed that afatinib followed by osimertinib resulted in a median OS of 41.3 months and a 2-year OS rate of 80% in patients with EGFR T790M–positive NSCLC.^3,4

Additionally, in patients with Del19-positive tumors, the median OS was 45.7 months (90% CI, 45.3-51.5) and the 2-year OS rate was 82%. The median time on treatment for afatinib and osimertinib was 28.1 months; for those with Del19 disease, it was 30.6 months. Following treatment with afatinib, the median time on osimertinib was 15.6 months in the overall patient population and a bit longer in those with Del19, at 16.4 months.

In the retrospective, observational, unblinded GioTag trial, sequential afatinib and osimertinib was given to a total of 203 patients with EGFR-mutant NSCLC who also had acquired T790M mutations. The majority of participants were administered the approved starting dose of afatinib at 40 mg daily (83.7%) and osimertinib at 80 mg daily (98%).

More than half of patients, or 58.8%, were Caucasian, 24.5% of patients were Asian, and 8.8% were African Americans (8.8%). Moreover, 15.2% of patients had an ECOG performance status of at least 2, while 10.3% had central nervous system metastases. Moreover, 73.5% of patients (n = 149) had Del19-positive tumors and 26.0% had L858R mutations; 1 patient had both abnormalities.

The first portion of the 2-stage process comprised a subsequent analysis in which investigators evaluated updated data from a patient subset for whom electronic health records were available.

All patients must have received osimertinib 10 months or longer before enrolling on the study to avoid early censoring and ensure mature data. The primary end point of the trial was TTF and an OS analysis was exploratory.

By April 2019, 85 patients (41.9%) had died, 26 (12.8%) were lost to follow-up, and 92 patients (45.3%) were alive; this included 63 (31.0%) who remained on osimertinib treatment. One patient was excluded from analysis because of conflicting data reports.

Additional data had demonstrated an updated median TTF of 28.1 months (90% CI, 26.8-30.3) with the treatment. Specifically in patients with Del19-positive tumors, the median TTF was 30.6 months (90% CI, 27.6-32.0).

At a median follow-up of 30.3 months, the overall median OS was 41.3 months (90% CI, 36.8-46.3); the median OS was even higher in patients with Del19-positive tumors, at 45.7 months (90% CI, 45.3-51.5).

The final analysis for the full patient population from the phase 3 GioTag study is anticipated later this quarter, according to Boehringer Ingelheim.

References

1. Feinberg B, Halmos B, Gucalp R, et al. Making the case for EGFR TKI sequencing in EGFR mutation-positive NSCLC: a GioTag study US patient analysis. Published online August 6, 2020. Future Oncol. doi:10.2217/fon-2020-0188
2. Additional analysis of real-world data confirms sequential Gilotrif followed by osimertinib provided a median overall survival of nearly four years in US-treate patients with EGFR mutation-positive NSCLC. News release. Boehringer Ingelheim. August 10, 2020. Accessed August 10, 2020. https://bit.ly/33YN4TV.
3. Updated real-world data shows Giotrif/Gilotrif (afatinib) followed by osimertinib provided a median overall survival of up to almost four years in patients with EGFR Del19 and T790M mutation-positive NSCLC. News release. Boehringer Ingelheim. August 2, 2019. Accessed August 10, 2020. https://bit.ly/2KksMIT. 
4. Hochmair MJ, Morabito A, Hao D, et al. Sequential afatinib and osimertinib in patients with EGFR mutation-positive non-small-cell lung cancer: updated analysis of the observational GioTag study. Published online August 2, 2019. Future Med. doi:10.2217/fon-2019-0346