4082 - Real-world (RW) treatment patterns and outcomes for second-line (2L) therapy and beyond in patients (pts) with epidermal growth factor receptor-mutated (EGFRm) advanced NSCLC receiving a first-line (1L) first- or second-generation (1G/2G) EGFR tyrosine kinase inhibitor (TKI)

Background

EGFR-TKIs are the preferred 1L therapy for pts with EGFRm metastatic NSCLC. However, treatment and survival in this population with 2L therapy and beyond are not well defined in the RW setting. To address this, we analysed RW cohort data in the USA, UK, Germany and France.

Methods

A retrospective chart review was conducted for 472 pts with EGFRm NSCLC receiving a 1L 1G / 2G EGFR-TKI (1 Jan 2015–31 Dec 2017). Data on 1L and 2L treatment and progression after 1L initiation (defined by clinical progression, start of 2L treatment or death before 2L treatment initiation) were extracted. 1L progression-free (PFS) and overall survival (OS) were estimated via Kaplan–Meier methods.

Results

Baseline characteristics at 1L: median age 62 yrs; 43% female; 61% current/former smokers; 60% Caucasian; 76% Exon 19 deletion. 1L EGFR-TKI treatments: 44% afatinib; 36% erlotinib; 21% gefitinib. Median duration of overall follow-up from start of 1L was 19.9 months (mo; range 0.3–50.3). Of 472 pts, 344 (73%) progressed on 1L treatment, including 158 who died during follow-up. 128 (27%) pts did not progress: 86 (18%) remained on 1L treatment and 42 (9%) pts discontinued 1L treatment before follow-up end. Median 1L PFS (95% CI) was 14.5 (13.3, 15.6) mo and median OS (95% CI) from start of 1L was 34.6 (29.5, 45.5) mo. Of 344 pts with 1L progression, 255 (74%) were tested for T790M; 129 (38%) were positive, of whom 97 received osimertinib (75%). Of 126 pts testing negative, 17 (13%) received osimertinib. Of 344 pts with 1L progression, 258 (75%) received 2L treatment, osimertinib-containing regimens being most common (n = 109/258, 42%). For 86 (25%) pts with 1L progression but no 2L treatment, 73 (85%) died and 13 (15%) were alive at follow-up end.

Conclusions

25% of pts progressing on 1L EGFR-TKIs did not receive 2L treatment (due to death in most cases). Furthermore, 25% of pts who progressed on 1L treatment and tested T790M positive did not receive osimertinib. Findings indicate that rates of resistance mutation testing and utilisation of effective EGFRm NSCLC therapies may be suboptimal.

Clinical trial identification

Editorial acknowledgement

Robert Harrison, PhD, of iMed Comms, Macclesfield, UK, an Ashfield Company; funded by AstraZeneca.

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

R. Shah: Honoraria (self), Travel / Accommodation / Expenses: Boehringer Ingelheim, Roche, AstraZeneca. N. Girard: Honoraria (self), Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): AstraZeneca, Boehringer Ingelheim. S.P. Nagar: Advisory / Consultancy, Employee of RTI-HS who provides consulting services to AstraZeneca: AstraZeneca. F. Griesinger: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca, Boehringer Ingelheim, Novartis, Pfizer, Celgene, Lilly, Roche, Merck Sharp & Dohme, Bristol-Myers Squibb, Takeda, Siemens; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: AbbVie. J. Roeper: Honoraria (institution): Boehringer Ingelheim, Roche, AstraZeneca. K. Davis: Research grant / Funding (institution): AstraZeneca, Novartis, Celgene, Sanofi, Pfizer, Amgen. N. Bakker: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. B. Thakrar: Full / Part-time employment: AstraZeneca. A. Taylor: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. All other authors have declared no conflicts of interest. J. Feliciano: Honoraria (self), Advisory / Consultancy: Merck; Honoraria (self), Advisory / Consultancy: Genentech; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Takeda; Honoraria (self), Advisory / Consultancy: Eli Lilly.