Treatment decisions, clinical outcomes, and pharmacoeconomics in the treatment of patients with EGFR mutated stage III/IV NSCLC in Germany: an observational study

Abstract

Background: We evaluated treatment decisions and outcomes in a cohort of predominately Caucasian patients with EGFR mutation-positive (EGFR Mut+) non-small-cell lung cancer (NSCLC).

Methods: REASON (NCT00997230) was a non-interventional study in German patients with stage IIIB/IV NSCLC. Secondary endpoints for EGFR Mut + NSCLC included progression-free survival (PFS), overall survival (OS), adverse event (AE) management, and pharmacoeconomic outcomes.

Results: Among 334 patients with EGFR Mut + NSCLC, tyrosine kinase inhibitors (TKIs) were the most common first-line therapy (56.6%, 53.0% gefitinib). Among patients who received TKIs/gefitinib before first disease progression, PFS was longer compared with those who did not receive a TKI (median 10.1/10.0 vs. 7.0 months; HR 0.67/0.69; log-rank p = 0.012/p = 0.022). OS was longer for those patients who ever received a TKI/gefitinib during their complete therapy course compared with those who never received a TKI (median 18.4/18.1 vs. 13.6 months; HR 0.53/0.55; p = 0.003/p = 0.005). Total mean first-line treatment healthcare costs per person were higher for those receiving TKIs (€46,443) compared with those who received chemotherapy (€27,182). Mean outpatient and inpatient costs were highest with chemotherapy. Rash, diarrhea, and dry skin were the most commonly reported AEs for patients receiving gefitinib.

Conclusions: In REASON, TKI therapy was the most common first- and second-line treatment for EGFR Mut + NSCLC, associated with increased drug costs compared with chemotherapy. Patients who received gefitinib or a TKI ever during their complete therapy course had prolonged PFS and OS compared with patients who did not receive a TKI.

Trial registration: The trial was registered on October, 2009 with ClinicalTrials.gov : https://ichgcp.net/clinical-trials-registry/NCT00997230?term=NCT00997230&rank=1.

Keywords: EGFR tyrosine kinase inhibitor; EGFR-mutations; Non-small cell lung cancer (NSCLC); Observational; REASON study.

Conflict of interest statement

Ethics approval and consent to participate

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

The opinion from the Ethics Committee of the coordinating investigator (Ärztekammer Sachsen-Anhalt) was sought for the final study protocol, including the final version of the Informed Consent Form. Notifications were sent to the Ethics Committees of all involved investigators. An Ethics Committee opinion was also sought for any amendment to the protocol in accordance with local requirements.

All patients provided written, informed consent.

This article does not contain any studies with animals performed by any of the authors.

Consent for publication

Not applicable

Competing interests

WS reports honoraria from, Roche, Lilly and Boehringer Ingelheim, consulting or advisory roles with Roche, Lilly and Boehringer Ingelheim and travel, accommodation or expenses from Boehringer Ingelheim. PS reports honoraria from AstraZeneca, Novartis, Roche, Amgen and Pfizer and consulting or advisory roles with AstraZeneca, Novartis, Amgen and Pfizer. WE reports honoraria from AstraZeneca, Eli Lilly, Boehringer Ingelheim, Pfizer, Novartis, Roche, Merck, Bristol-Myers Squibb, Amgen, GlaxoSmithKline, Astellas, Bayer, Teva, Merck Serono, Daichi Sankyo and Hexal and consulting or advisory roles with AstraZeneca, Eli Lilly, Boehringer Ingelheim, Novartis, Pfizer, Roche, Merck, Bristol-Myers Squibb, Astellas, Bayer, Teva and Daichi Sankyo. UZ is an employee of iOMEDICO AG. LM is an employee of AstraZeneca. MT reports honoraria from AstraZeneca, Roche, Bristol-Myers Squibb, MSD, Lilly, Novartis and Pfizer and consulting or advisory roles with AstraZeneca, Bristol-Myers Squibb, MSD, Lilly, Novartis and Roche. MD reports no potential conflicts of interest.

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Figures

Fig. 1

Second- and third-line treatment in patients with EGFR Mut + NSCLC More than one agent could be reported. *Other = experimental (n = 4 s-line), afatinib (n = 3 s-line), experimental afatinib (n = 2 third-line), gefitinib/placebo (n = 1 s-line), trofosfamide (n = 1 s-line). †Data for patients receiving second-line treatment are a combination of planned treatment (n = 63 patients who did not consent to collection of data for second-line treatment) and actual treatment (n = 59 patients who consented to collection of data for second and subsequent lines of treatment). Mut+, mutation-positive; NSCLC, non-small-cell lung cancer

Fig. 2

KM estimates of PFS and OS: patients with EGFR Mut + advanced NSCLC by therapy Kaplan-Meier estimates of progression-free survival (a and b) and overall survival (c and d), of patients with EGFR Mut + advanced NSCLC who received either a TKI (a and c) or gefitinib (b and d) prior to first disease progression compared with those patients who did not receive a TKI prior to first disease progression. KM, Kaplan-Meier; Mut+, mutation-positive; NSCLC, non-small-cell lung cancer; TKI, tyrosine kinase inhibitor

Fig. 3

KM estimates of OS: patients with EGFR Mut + advanced NSCLC who ever received a TKI Kaplan-Meier estimates of overall survival of patients with EGFR Mut + advanced NSCLC who ever received either a TKI (a) or gefitinib (b) during their entire course of treatment compared with those who did not receive a TKI. KM, Kaplan-Meier; Mut+, mutation-positive; NSCLC, non-small-cell lung cancer; TKI, tyrosine kinase inhibitor