Efficacy and safety of afatinib in Chinese patients with EGFR-mutated metastatic non-small-cell lung cancer (NSCLC) previously responsive to first-generation tyrosine-kinase inhibitors (TKI) and chemotherapy: comparison with historical cohort using erlotinib

Victor H F Lee, Dennis K C Leung, Tim-Shing Choy, Ka-On Lam, Pui-Mei Lam, To-Wai Leung, Dora L W Kwong, Victor H F Lee, Dennis K C Leung, Tim-Shing Choy, Ka-On Lam, Pui-Mei Lam, To-Wai Leung, Dora L W Kwong

Abstract

Background: Afaitnib has shown anti-tumor activity against metastatic EGFR-mutated NSCLC after prior failure to first generation EGFR-TKI and chemotherapy. We prospectively evaluated the efficacy and safety of afatinib in Chinese patients who previously failed first-generation TKI and chemotherapy under a compassionate use program (CUP) and compared to the erlotinib cohort.

Methods: Patients who suffered from metastatic EGFR-mutated NSCLC previously responsive to first-generation TKI and chemotherapy received afatinib until progression, loss of clinical benefits or intolerable toxicity. Treatment response, survival and safety were evaluated and compared to the erlotinib cohort.

Results: Twenty-five and 28 patients received afatinib and erlotinib respectively. More patients in the afatinib group had worse performance status (ECOG 2) than the erlotinib group (p = 0.008). After a median follow-up of 12.1 months, afatinib demonstrated comparable objective response rate (ORR) (20.0% vs. 7.1%, p = 0.17) but significantly higher disease control rate (DCR) (68.0% vs. 39.3%, p = 0.04) compared to erlotinib. Median progression-free survival (PFS) (4.1 months [95% CI, 2.7-5.5 months] vs. 3.3 months [95% CI, 2.2-4.3 months], p = 0.97) and overall survival (OS) were not different between the two groups (10.3 months [95% CI, 7.5-13.0 months] vs. 10.8 months [95% CI, 7.4-14.2 months], p = 0.51). Multivariate analyses revealed that age ≤ 70 years and time to progression (TTP) ≥ 18 months for the 1st TKI therapy were prognostic of PFS (p = 0.006 and p = 0.008 respectively). Afatinib caused less rash (60.0% vs. 67.9%, p = 0.04) but more diarrhea (60.0% vs. 10.7%, p = 0.002) compared to erlotinib.

Conclusion: Afatinib produced encouraging clinical efficacy as 2nd TKI therapy with manageable safety profiles in our Chinese patients after failure to another TKI and systemic chemotherapy. This study was registered at ClinicalTrials.gov (NCT02625168) on 3rd December 2015.

Figures

Fig. 1
Fig. 1
Kaplan-Meier plots illustrating survival outcomes in patients treated with afatinib or erlotinib as 2nd tyrosine-kinase inhibitor (TKI) therapy after previous failure to first-generation TKI and chemotherapy. a. Progression-free survival (PFS) in the afatinib and erlotinib group. b. Overall survival (OS) in the afatinib and erlotinib group. c. PFS comparing those whose time to progression to 1st TKI therapy was ≥18 months versus those whose time to progression to 1st TKI therapy was <18 months
Fig. 2
Fig. 2
Computed tomography images of one of our study patients with metastatic bronchoalveolar carcinoma which harbored exon 19 deletion treated with afatinib as 2nd TKI therapy after failure to gefitinib and chemotherapy. a. Baseline images showing diffuse ground glass opacities representing tumor infiltrates in lower lobes of both lungs. b. CT images at 3 months after afatinib showing significant reduction of tumor infiltrates. c. CT images at 6 months after afatinib showing further response and tumor shrinkage to afatinib

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