Patient populations by geography

Asian patients in the observational GioTag study

The observational GioTag study (NCT03370770) investigated outcomes in patients with EGFR mutation-positive non-small cell lung cancer (NSCLC) who were treated with sequential afatinib* and osimertinib in a real-world clinical setting. In the final analysis of Asian patients (n=50), median time on treatment was 37.1 months (90% confidence interval [CI]: 28.1–40.3) and median overall survival (OS) was 44.8 months (90% CI: 37.0–57.8).¹ Among Asian patients with del19-positive tumors (n=31), median time on treatment was 40.0 months (90% CI: 36.4–45.0) and median OS was 45.7 months (90% CI: 38.2–57.8).¹

These results suggest that sequential afatinib followed by osimertinib can be a feasible and effective therapeutic strategy in Asian patients with EGFR mutation-positive NSCLC who develop the T790M resistance mutation.¹

OS for Asian patients treated with sequential afatinib and osimertinib in the GioTag study¹

Asian patients in LUX-Lung 3 and 7

Data from LUX-Lung 3 (72% Asian population) and LUX-Lung 7 (57% Asian population) indicate that the efficacy of afatinib in Asian patients with NSCLC is in line with that seen in other study populations, with EGFR mutation status, rather than ethnicity, being a key predictor of efficacy.^2,3 For instance, the hazard ratio (HR) for progression-free survival (PFS) in LUX-Lung 7 was 0.72 for non-Asian patients and 0.76 for the Asian population.³

Japanese patients in LUX-Lung 3

A subgroup analysis of Japanese patients who participated in LUX-Lung 3 showed a significant increase in PFS with afatinib compared with cisplatin/pemetrexed in all Japanese patients, as well as in patients with common EGFR mutations. OS was significantly longer with afatinib than with chemotherapy in patients with del19 mutations (46.9 vs 31.5 months), but did not differ significantly between treatment arms in patients with L858R mutations.⁴

PFS outcomes for Japanese patients in LUX-Lung 3

OS outcomes for Japanese patients with del19 mutations in LUX-Lung 3

Chinese patients in LUX-Lung 6

The LUX-Lung 6 Phase III trial was conducted in Asian countries; 90% of randomized patients were of Chinese ethnicity.

A post-hoc analysis of the Chinese patient subgroupt demonstrated that, overall, afatinib significantly increased PFS compared with gemcitabine/cisplatin: median 11.0 vs 5.6 months; HR=0.30; 95% CI: 0.21–0.43; p<0.0001. The objective response rate (ORR) and disease control rate (DCR) were also significantly higher with afatinib than with gemcitabine/cisplatin in the overall population: ORR,  67% vs 24%, respectively; odds ratio=6.94; 95% CI: 4.05–11.88 (p<0.0001); DCR, 92% vs 77%, respectively; odds ratio=3.45; 95% CI: 1.77–6.71 (p=0.0003).⁵  

Although there was no significant difference in OS between the treatment arms for the overall population (p=0.7765), in patients with EGFR del19 mutations OS afatinib significantly improved OS compared with gemcitabine/cisplatin: median 31.6 vs 16.3 months, respectively; HR=0.61; 95% CI: 0.41–0.91 (p=0.0146).⁵ Afatinib also significantly increased PFS compared with gemcitabine/cisplatin in in patients with common (EGFR del19 or L858R) mutations: median 11.0 vs 5.6 months; HR=0.26; 95% CI: 0.18–0.37; p<0.0001).⁵

There were no unexpected safety findings with afatinib in Chinese patients.⁵

Chinese patients with squamous NSCLC in LUX-Lung 8

A post-hoc subgroup analysis of data from 67 Chinese patients with advanced squamous NSCLC in LUX-Lung 8 confirmed that the efficacy, safety and tolerability of afatinib in this subgroup are in line with that seen in the overall study population.⁶ Trends favoring afatinib versus erlotinib in terms of PFS (median 2.8 vs 2.8 months; HR=0.70; 95% CI: 0.38–1.27), OS (median 10.8 vs 8.2 months; HR=0.69; 95% CI: 0.39–1.21), tumor control and improvements in patient-reported outcomes (PROs) were comparable to those in the overall study population.⁶

The long-term benefit of afatinib appeared more pronounced in the Chinese subgroup compared with the overall LUX-Lung 8 population. Four of the 36 Chinese patients (11%) treated with afatinib were long-term responders who received afatinib for ≥12 months, compared with 21/398 (5%) of the overall study population.⁶ At the data cut-off, three of the four Chinese long-term responders were still on treatment, while the fourth had disease progression.⁶

Asian results from an afatinib compassionate use program in patients who progressed following prior therapies

A subanalysis was performed in patients who had participated in the afatinib compassionate use program in Asian countries (N=2,242) and received a median of three lines of prior therapy.⁷ Response data were available from 431 patients; ORR was 24.4% in the overall population, 27.4% in patients with common EGFR mutations (n=230) and 28.1% in patients with uncommon EGFR mutations (n=32).⁷ Median time to treatment failure with afatinib was 7.6 months in 1,550 patients for whom data were available, 6.4 months in patients with common EGFR mutations (n=692), 8.4 months in patients with uncommon EGFR mutations (n=83) and 12.2 months in patients with HER2 mutations.⁷ The safety profile of afatinib in Asian patients was consistent with that in non-Asian patients.