365P - Patterns of progression on first-line osimertinib in patients with EGFR mutation-positive advanced non-small cell lung cancer (NSCLC): A Swiss cohort study

Background

Osimertinib (osi) is a third-generation EGFR tyrosine kinase inhibitor (TKI) with antitumor activity in non-small cell lung cancer (NSCLC) against activating EGFR and T790M mutation. The incidence of oligo-PD on first-line osi is unknown.

Methods

We retrospectively analyzed patients (pts) with advanced NSCLC and an EGFR mutation who received first line osi at 13 Swiss centers. Oligo-PD was defined as PD in ≤ 5 lesions. The rate, outcomes of pts with oligo-PD vs. systemic-PD (i.e. PD in >5 lesions) and patterns of progression were analyzed.

Results

A total of 138 pts were included. Median age was 68.4 years (range: 38.0-93.3). There were 58% females, 81% had a PS ≤ 1, 60%/20%/9% were never/former/current smokers. Seventy-eight (57%) of pts had EGFR exon 19 deletion, 47 (34%) L858R exon 21 mutation and 12 (9%) other EGFR mutations. Median follow-up was 31.4 months (IQR: 22.0-48.3). Median progression-free survival (PFS) was 18.5 (95% CI, 14.5-21.0) vs. 8.7 (95% CI, 4.5-15.6) months for activating vs. other EGFR mutations. Median overall survival (OS) was 51.5 months (95% CI, 36.2-65.0) for all pts and 51.6 months (95% CI, 38.4-65.0) for pts with activating mutations. At data-cut off 73 were PD, 75% with oligo- and 25% with systemic PD. Number of progressive lesions in oligo-PD were 1 (37%), 2 (25%), 3 (6%), 4 (7%) and 5 (1%). Main sites of PD were lungs (52%), brain (29%) and bones (25%). Median time until treatment failure in oligo-PD vs. systemic-PD pts was 20.6 months (95% CI, 16.1-28.6) vs. 10.8 months (95% CI, 8.3-13.2, p<0.001). Twenty-three pts (42%) with oligo-PD received local ablative treatment (LAT). Pts with vs. without LAT had similar OS (51.6 [95% CI, 22.4-65.0] vs. 51.4 [95% CI 38.4-65.3] months, p=0.65).

Conclusions

We observed a very favorable OS of 51.5 months in our real-world Swiss cohort of pts treated with first line osi. As previously reported in the second line we report a high rate of oligo-PD of 75%. Time to treatment failure of pts with oligo-PD was significantly longer compared to pts with systemic PD (20.6 vs. 10.8 months, p<0.001). Surprisingly, the incidence of PD in the brain was 29%, indicating the importance of regular brain imaging. The role of LAT needs to be explored in future studies.

Clinical trial identification

2020-02986 EKOS 20/239.

Editorial acknowledgement

Legal entity responsible for the study

Cantonal Hospital St. Gallen, Department of Oncology and Haematology.

Funding

AstraZeneca.

Disclosure

A. Schuler: Other, Institutional, Other, Travlel support: Takeda ; Other, Institutional, Funding, unrestricted funding/financial support for the study: AstraZeneca; Other, Institutional, Invited Speaker, Invited Speaker for Institution: Amgen. S. Schmid: Financial Interests, Institutional, Research Grant: AstraZeneca, BMS, Janssen, vonTobel Stiftung, Fill the Gap, Altschüler Stiftung; Financial Interests, Institutional, Advisory Board: BMS, MSD, AstraZeneca, Boehringer Ingelheim; Financial Interests, Institutional, Other, Travel support: Takeda, Boehringer Ingelheim, MSD. O. Gautschi: Financial Interests, Institutional, Other, Consultant: Amgen, Lilly; Financial Interests, Institutional, Advisory Board: BAYER, Novartis; Financial Interests, Institutional, Invited Speaker: LILLY. L.A. Mauti: Financial Interests, Personal, Advisory Role: AstraZeneca, BMS, Pfizer, Roche, Takeda, MSD, Sanofi, Merck; Financial Interests, Personal, Funding: AstraZeneca; Financial Interests, Personal, Other, Travel Support: AstraZeneca; Financial Interests, Personal, Invited Speaker: Takeda, MSD, AstraZeneca, Novartis. S.I. Rothschild: Financial Interests, Institutional, Other, Honoraria: Roche, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, MSD Oncology, Novartis, Amgen, Lilly, Eisai, Merck Serono, Pfizer, Takeda, Bayer, Janssen Oncology, Otsuka, PharmaMar, Sanofi; Financial Interests, Institutional, Advisory Role: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Pfizer, Eisai, Lilly, Merck Serono, MSD Oncology, Novartis, Roche Pharma AG, Takeda, Otsuka; Financial Interests, Institutional, Advisory Board: Amgen; Financial Interests, Institutional, Funding: AbbVie, Bristol Myers Squibb, AstraZeneca, Boehringer Ingelheim, Merck Serono, Roche Pharma AG; Financial Interests, Personal, Other, Travel Support: Sanofi; Financial Interests, Institutional, Other, Travel Support: Roche Pharma AG, Bristol Myers Squibb, MSD Oncology, AstraZeneca, Takeda, Boehringer Ingelheim, Amgen. A. Addeo: Financial Interests, Personal and Institutional, Advisory Board: MSD Oncology, Roche, Takeda, Pfizer, Bristol Myers Squibb, AstraZeneca, Eli-Lilly; Financial Interests, Personal and Institutional, Invited Speaker: Eli Lilly, AstraZeneca, Amgen. W. Janthur: Other, Personal, Advisory Board: MSD, Roche, Amgen, Takeda. C. Britschgi: Financial Interests, Personal, Advisory Role: AstraZeneca, Pfizer, Roche, Takeda, Janssen-Cilag, Boehringer Ingelheim, Roche; Financial Interests, Personal, Other, Travel Support: AstraZeneca, Takeda. M. Frueh: Financial Interests, Institutional, Other, Grants: BMS, AstraZeneca; Financial Interests, Institutional, Advisory Role: AstraZeneca, Merck Sharp&Dohme, Bristol Myers Squibb, Boehringer Ingelheim, Pfizer, Takeda, Roche; Financial Interests, Institutional, Other, Payment for expert testimony: Takeda, Roche; Financial Interests, Institutional, Other, Travel Support: Merck; Financial Interests, Institutional, Advisory Board: Roche. All other authors have declared no conflicts of interest.