678P - Ramucirumab plus Erlotinib (RAM+ERL) for advanced non-small cell lung cancer (NSCLC) harboring EGFR L858R mutation (L858R mut): A multicenter retrospective observational cohort study (REAL-SPEED)

Background

Generally, NSCLC patients (pts) with L858R mut is associated with poorer efficacy of EGFR-TKIs than those with ex19del. However, in RELAY study, RAM+ERL showed comparable efficacy in pts with L858R mut and those with ex19del (median progression-free survival [PFS]: 19.6 vs. 19.4 months [M]). Thus, we planned a retrospective observational cohort study to confirm the efficacy and safety for Japanese pts with L858R mut in the real-world (RW).

Methods

Conducted at 47 sites, this study evaluated pts treated with 1L RAM+ERL in clinical practice between Dec 1, 2020, and Aug 31, 2023. Time to treatment of failure (TTF), PFS, PFS2, and overall survival (OS) as well as adverse events (AEs) were analyzed.

Results

Of the 168pts enrolled, 168 who appropriately met eligibility criteria were finally analyzed. Median age was 72 (33-87) years; ECOG PS of 0/1/2 was 45%/51%/4%, respectively; female was 64%; non-smoker was 66%; brain metastasis was 26%; and PD-L1 expression of 0%/1-49%/≥50%/unknown was 40%/36%/15%/9%, respectively. Among median follow-up time of 21.0 M, events of TTF, PFS, PFS2, and OS occurred in 65%, 43%, 29%, and 20%, respectively, resulting in median TTF, PFS, and PFS2 of 12.2M (95%CI, 9.5-15.5), 17.4M (95%CI, 14.8-24.8), and 27.0M (95%CI, 19.9-NA), respectively, and 2-year OS rate of 78%. Pts with PD-L1 expression of 0%/1-49%/≥50%/unknown exhibited median PFS of 20.4M/21.2M/14.8M/12.9M, respectively (log-rank p=0.11). The most frequent AEs were dermatitis acneiform (71%) and paronychia (43%). Treatment discontinuations were due to AEs (48 pts, 29%) and disease progression (55pts, 33%), of which 31 and 29 pts received osimertinib in 2^nd or later line, respectively, leading to a total treatment rate of 58% (60/103 pts) with osimertinib.

Conclusions

This is the first RW study of RAM+ERL for pts with L858R mut. Although AE discontinuation frequency was notable, PFS was comparable to the result of RELAY study. The addition of RAM to ERL indicated consistent benefit against NSCLC pts harboring L858R mut regardless of PD-L1 expression. Furthermore, 1L RAM+ERL would provide more clinical benefit in terms of sequence therapy.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Eli Lilly Japan.

Disclosure

M. Ishihara: Financial Interests, Institutional, Sponsor/Funding: Eli Lilly Japan. N. Seki: Financial Interests, Personal and Institutional, Sponsor/Funding: Eli Lilly Japan. All other authors have declared no conflicts of interest.