330P - A real-world multi-center prospective observational study of atezolizumab (Atezo) + bevacizumab (Bev) + carboplatin (CBDCA) + paclitaxel (PTX) (ABCP) in patients (pts) with advanced EGFR-mutated (EGFRm) NSCLC after EGFR-TKIs failure

Background

Single-agent programmed death (PD)-1/PD-ligand (L) 1 inhibitors are known to have poor clinical outcomes in pts with advanced EGFRm NSCLC. Otherwise a subset analysis of the IMpower150 trial suggested the substantial efficacy of ABCP in the same pts’ population. We conducted a prospective observational study to evaluate the safety and effectiveness of ABCP in pts with advanced EGFRm NSCLC in a real world setting.

Methods

Eligible criteria included pts aged 20 or older, with nonsquamous EGFRm NSCLC treated with at least one prior EGFR-TKI, and who have a plan to receive the combination therapy of Atezo (1200 mg/body, day 1), Bev (15 mg/kg, day 1), CBDCA (AUC 6 mg/mL/min, day 1) and PTX (175 mg/m2, day 1) every 3 weeks up to 4 cycles followed by Atezo plus Bev until loss of clinical benefit in their clinical practice. Written informed consent was obtained from all included pts. The primary endpoint was progression-free survival (PFS). The major secondary endpoints included overall survival (OS), overall response rate (ORR), and safety.

Results

From 38 centers in Japan, 142 pts were enrolled (median age 69 [IQR 60–72], 57% were female, 97% were ECOG PS of 0 or 1, 49% were Ex19del and 39% were L858R, 54% were never smoker, 81% were de novo stage III or IV), and 139 pts were eligible for analysis. At data cutoff (Nov. 21, 2021), median follow-up was 17.3 months. Median PFS was 5.4 month (95% CI, 4.56-6.46) and median OS was 17.4 month (95% CI, 13.7-not reached). ORR was 33.8% (95% CI, 26.0-42.3). Concomitant autoimmune disease was associated with a favorable PFS (hazard ratio, 0.43 (95%CI, 0.16-1.17)). The frequent grade (G) ≥ 3 AEs (≥ 20%) were neutropenia (43.2%), leukopenia (42.4%), febrile neutropenia (23.7%) and lymphopenia (21.6%). Peripheral sensory and motor neuropathy (all Gs / ≥ G 3) occurred in 43.2/5.8% and 10.1/2.2% of pts, respectively. Three interstitial lung disease (G1:2, G3:1) was observed.

Conclusions

ABCP for EGFRm NSCLC pts after EGFR-TKIs failure showed moderate effectiveness with good tolerability, and can be a treatment option in a real world setting.

Clinical trial identification

UMIN Clinical Trials Registry (UMIN-CTR): UMIN000037967.

Editorial acknowledgement

Legal entity responsible for the study

Takayasu Kurata (Principal Investigator).

Funding

Chugai Pharmaceutical Co. Ltd.

Disclosure

S. Kuyama, H. Yoshioka, H. Kaneda, S. Miura, N. Katakami, A. Tamiya, H. Tanaka, Y. Fujisaka, K. Azuma, A. Hata, K. Sawa: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical. T. Yokoyama, T. Kurata: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical; Financial Interests, Institutional, Research Grant: Chugai Pharmaceutical. All other authors have declared no conflicts of interest.