363P - A multicentre, real-world observational study of efficacy and safety of first-line osimertinib treatment in patients with epidermal growth factor receptor (EGFR) activating mutation-positive advanced non-small cell lung cancer (Reiwa study)

Background

Osimertinib is a third-generation, irreversible EGFR-tyrosine kinase inhibitor (TKI) that selectively inhibits both EGFR-TKI-sensitizing and EGFR-T790M-resistant mutations. In a phase III trial (FLAURA), osimertinib showed efficacy superior to that of first-generation gefitinib and erlotinib, with a similar safety profile and lower rates of serious adverse events. Osimertinib is currently being used as the first-line treatment for patients with advanced EGFR mutation-positive NSCLC. However, the efficacy and safety of osimertinib treatment in clinical practice have not been fully verified.

Methods

We performed a multicenter, prospective cohort study to evaluate the activity of osimertinib treatment in clinical practice. EGFR mutation-positive NSCLC patients who started EGFR-TKI treatment from September 2018 to August 2020 were enrolled, and first-line osimertinib monotherapy was selected among them.

Results

Of the total enrollment of 659 patients treated with EGFR-TKIs, osimertinib monotherapy was 583 (88%); their median age was 72 years (range: 30-95), male / female: 38.4 / 61.6%, DEL / L858R / others: 48.9 / 45.6 / 5.5%, PS 0 / 1 / 2 / 3 / 4: 37.1 / 48.2 / 10.3 / 3.4 / 0.3%. The overall objective response rate (ORR) was 68.1% (95% CI: 64.1-71.9). The median progression-free survival (PFS) was 20.0 months (95% CI: 17.6-21.7) and the survival rate at 24 months was 72.4% (95% CI: 68.4-76.0). The PFS by mutation type was 23.5 months (95% CI: 20.9-27.4) for exon 19 deletion and 17.0 months (95% CI: 15.2-19.7) for L858R point mutation in exon 21. Grade 3 or higher adverse events were observed in 22.6%, and toxicity discontinuation was observed in 15.8%. Pneumonitis was 12.9% in any grades and 3.1% in grade 3 and above. 82 patients with PS 2 or higher had an ORR of 55.8%, PFS of 13.8 months, 18.4% toxicity discontinuation, and 9.3% had pneumonitis in any grade and 4.7% in grade 3 and above.

Conclusions

Osimertinib showed promising activity with a manageable safety profile in clinical practice, even for patients with poor PS, consistent with effects to previous clinical trials.

Clinical trial identification

UMIN-CTR Clinical Trial: UMIN000038683 Release date: 2019/11/26.

Editorial acknowledgement

Legal entity responsible for the study

Public Health Research Center Comprehensive Support Project for Oncology Research.

Funding

This study was sponsored by the Public Health Research Foundation under the funding support from AstraZeneca.

Disclosure

K. Naoki: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical, Nippon Boehringer Ingelheim, AstraZeneca, Bristol Myers Squibb; Financial Interests, Institutional, Other: Ono Pharmaceutical, Taiho Pharmaceutical, Parexel International Inc. K. Yoh: Financial Interests, Personal, Invited Speaker: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai Pharmaceutical, Daiichi sankyo, Janssen, Kyowa kirin, Lilly, Novartis, Taiho; Financial Interests, Institutional, Principal Investigator: AbbVie, AstraZeneca, Daiichi Sankyo, Lilly, MSD, Pfizer, Taiho, Takeda. K. Usui: Financial Interests, Personal, Invited Speaker: AstraZeneca, Chugai, Boehrlnger Ingerlheim, Phizer, MSD, Eli Lilly, Novartis. Y. Hosomi: Financial Interests, Personal, Invited Speaker: AstraZeneca, Eli Lilly Japan, Taiho Pharmaceutical, Chugai Pharmaceutical, Ono Pharmaceutical, Bristol Myers Squibb, Kyowa Kirin, CSL Behring. K. Kishi: Financial Interests, Personal, Invited Speaker: AstraZeneca. G. Naka: Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Personal, Invited Speaker: AstraZeneca. K. Watanabe: Financial Interests, Personal, Invited Speaker: AstraZeneca, Taiho Pharmaceutical, Chugai Pharmaceutical, Ono Pharmaceutical, MSD, Pfizer, Boehringer Ingelheim. H. Kunitoh: Financial Interests, Personal, Invited Speaker: AstraZeneca, Boehringer Ingelheim, Chugai, Taiho, Daiichi-Sankyo, Johnson and Johnson. All other authors have declared no conflicts of interest.