Different stories for different EGFR exon 19 deletion variants

abstracts

Honoraria (self): Bristol-Myers Squibb; Honoraria (self): GlaxoSmithKline; Honoraria (self): Hoffmann La Roche; Honoraria (self): Lilly; Honoraria (self): Merck Sharp Dohme; Honoraria (self): Novartis; Honoraria (self): Pfizer; Honoraria (self): Takeda. S. Bouee: Full / Part-time employment: CEMKA. D. Moro-Sibilot: Honoraria (self), Honoraria (institution): AstraZeneca; Honoraria (self), Advisory / Consultancy: Boehringer Ingelheim; Honoraria (self), Honoraria (institution): BristolMyers Squibb; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Lilly; Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Honoraria (institution): Roche; Honoraria (self), Advisory / Consultancy: Takeda; Honoraria (self), Advisory / Consultancy: AbbVie. C. Emery: Full / Part-time employment, CEMKA received a grant from Boehringer Ingelheim to perform the statistical analysis of this study : CEMKA. K. Le Lay: Full / Parttime employment: Boehringer Ingelheim. L. Luciani: Full / Part-time employment: Boehringer Ingelheim. C. Maritaz: Full / Part-time employment: 4. Boehringer Ingelheim. C. Chouaid: Honoraria (self): AstraZeneca; Honoraria (self): Boehringer Ingelheim; Honoraria (self): GlaxoSmithKline; Honoraria (self): Roche; Honoraria (self): Sanofi; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Lilly; Honoraria (self): Novartis; Honoraria (self): Pfizer; Honoraria (self): Takeda; Honoraria (self): Bayer; Honoraria (self): Amgen.

1529P

Phase II study of osimertinib in NSCLC patients with EGFR exon 20 insertion mutation: A multicenter trial of the Korean Cancer Study Group (LU17-19)

T.M. Kim1, C-Y. Ock1, M. Kim2, S.H. Kim3, B. Keam1, Y.J. Kim3, D-W. Kim1, J-S. Lee4, D.S. Heo1 1 Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea, 2Seoul National University Hospital, National University College of Medicine, Seoul, Republic of Korea, 3Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea, 4Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea Background: Osimertinib is an oral, potent, irreversible EGFR tyrosine kinase inhibitor (TKI) selective for sensitizing EGFR and EGFRT790M mutations and approved for the first-line treatment of patients with sensitizing EGFR-mutant NSCLC. EGFR exon 20 insertion mutations account for up to 4% of all EGFR mutations and are generally resistant to EGFR TKIs. Although osimertinib is active against in vitro models of EGFR exon 20 insertion mutation, its efficacy has not been prospectively studied. This phase II study has been performed to evaluate the efficacy of osimertinib in NSCLC patients with EGFR exon 20 insertion mutation who failed to standard chemotherapy (ClinicalTrials.gov, NCT03414814). Methods: Patients received osimertinib 80mg orally once daily until disease progression, unacceptable toxicities, withdrawal, or no clinical benefits. Primary end point was investigator-assessed, confirmed objective response rate (ORR) as defined by RECIST version 1.1. Secondary end points were safety profiles, progression-free survival (PFS), overall survival (OS), and duration of response. Results: Between Jan 2018 and Feb 2019, 15 patients received osimertinib as secondline (20%, n ¼ 3) and  third-line (n ¼ 12) at stage 1 according to Simon’s minimax two-stage design (P0¼0.10, P1¼0.30; a ¼ 0.05, b ¼ 0.20). Median age was 61 years and female were 66.7%. ORR was 0% with mostly disease stabilization (stable disease, 46.7%, n ¼ 7). Three patients who had EGFR exon 20 insertions at M766, A767, and unknown sites were still receiving osimertinib at the cut-off date (disease stabilization, 12, 7, and 7 months, respectively). Median PFS and OS were 3.5 months (95% CI 1.6-

v628 | NSCLC, Metastatic

not reached) and not reached (1-year OS rate, 56.3%), respectively. Disease control rate at 6 months was 31.1%. The most frequently observed adverse events (AEs, all grades, %) were nausea (20%, n ¼ 3), vomiting (20%, n ¼ 3), anemia (13.3%, n ¼ 2), and fever (13.3%, n ¼ 2). Conclusions: Osimertinib is well tolerated, but has limited clinical activity in NSCLC patients with EGFR exon 20 insertion mutation who failed to standard chemotherapy. Clinical trial identification: NCT03414814. Legal entity responsible for the study: Tae Min Kim. Funding: AstraZeneca. Disclosure: T.M. Kim: Advisory / Consultancy, without any compensation: AstraZeneca; Advisory / Consultancy, without any compensation: Novartis; Advisory / Consultancy, without any compensation: Sanofi; Advisory / Consultancy, without any compensation: Bayer; Research grant / Funding (self), outside this work: AstraZeneca; Advisory / Consultancy, without any compensation: Takeda. B. Keam: Research grant / Funding (self), outside this work: AstraZeneca; Research grant / Funding (self), outside this work: MSD; Research grant / Funding (self), outside this work: ONO; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: MSD; Advisory / Consultancy: Genexine. D. Kim: Advisory / Consultancy, without any compensation: AstraZeneca; Advisory / Consultancy, without any compensation: Novartis; Advisory / Consultancy, without any compensation: Takeda. All other authors have declared no conflicts of interest. Linguistic correction

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Different stories for different EGFR exon 19 deletion variants

C. Zhao1, T. Jiang2, J. Li2, Y. Wang2, M. Qiao2, X. Chen3, C. Su2, C. Zhou2, X. Li4 Lung Cancer and Immunology, Shanghai Pulmonary Hospital, Tongji University, Shanghai, China, 2Oncology, Shanghai Pulmonary Hospital, Tongji University, Shanghai, China, 3Department of Oncology, Shanghai Pulmonary Hospital, Tongji University, Shanghai, China, 4Department of Lung Cancer and Immunology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China

1

Background: Epidermal growth factor receptor (EGFR) exon 19 deletion (19del) and L858R mutation respond differently to first generation tyrosine kinase inhibitors (TKIs), however, the clinical outcomes of different 19del variants to TKIs and the resistance patterns are not well studied. Methods: From April 2016 to August 2017, 194 treatment-naive NSCLC patients detected as EGFR exon 19 deletions using amplification-refractory mutation system were included. DNA sequencing was used to detect the subtypes. Clinicopathological features as well as patients’ outcomes to first-line EGFR TKIs were analyzed. Results: Twelve EGFR 19del variants were confirmed in 169 of the 194 samples. Among these, p.E746_A750del was the most frequent variant (147/169, 87.0%). p.E746_A750del was more frequently found in females (p ¼ 0.008) and never smokers (p ¼ 0.004) than other deletions. And deletions starting with E746 was also more frequently found in these patients than L747 (p ¼ 0.014 and p ¼ 0.018, respectively). Interestingly, T790M occurred more frequently in p.E746_A750del than other deletions (64.3% vs 18.2%, p ¼ 0.017) or deletions started with E746 than L747 (63.6% vs 11.1%, p ¼ 0.012). Patients harboringdeletions starting with L747 plus insertions had significantly shorter progression-free survival (PFS) than no insertions (8.3m vs 15.0m, p ¼ 0.008), as well as other subtypes (8.3m vs 12.8m, p ¼ 0.016). Multivariate analysis showed that only L747 deletion plus insertions and age were independent factors influencing PFS (p ¼ 0.015 and 0.046, respectively). Conclusions: p.E746_A750del was the most frequent variant of EGFR exon 19del in NSCLC patients. It was more frequently found in female and never smoking patients. T790M mutation had a higher ratio in these patients when they were resistant to firstline TKI treatment. Deletions starting with L747 plus insertions had shorter PFS than other variants. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.

Volume 30 | Supplement 5 | October 2019

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mechanism of resistance. While osimertinib may also be given as first-line treatment, limited data exists on the real life effectiveness of the TKIs sequencing approach: TKI 1G or 2G followed by osimertinib. The French National medico administrative claim database (SNDS) offers the opportunity to estimate the effectiveness parameters for these patients in France. Methods: Based on SNDS, a historic cohort of patients with a diagnosis of EGFRmutated NSCLC treated, after a first-line with a TKI 1G or 2G, with osimertinib in second-line between 2015 and 2017 was extracted. Follow-up was conducted until December 31st 2017. Patients’ characteristics, Time on treatments and Overall survival were analysed. Results: 1,404 NSCLC patients have been treated with osimertinib in the database between 2015 and 2017. Among them, 509 had a previous treatment with TKI 1G or 2G without any other anticancer drug before osimertinib initiation, and constitute the analysed population. Mean age was 70.9 (29.1% were above 80 years old), 25.7% were males. Median time on TKI treatment (between the beginning of the first TKI 1G or 2G until discontinuation of osimertinib) was not reached but the percentages of patients still treated were: 83.8% at 24 months and 75.5% at 36 months. Median overall survival was not reached but the percentages of patients still alive were: 79.6% at 24 months and 70.3% at 36 months. Updated data will be presented at the meeting. Conclusions: Our cohort confirms the prolonged time on TKI treatment and survival rates of patients receiving TKI 1G or 2G followed by osimertinib in a real life setting. Legal entity responsible for the study: The authors. Funding: Boehringer Ingelheim. Disclosure: N. Girard: Honoraria (self): AstraZeneca; Honoraria (self): Boehringer Ingelheim;

Annals of Oncology