Intracranial Efficacy of Atezolizumab, Bevacizumab, Carboplatin, and Paclitaxel in Real-World Patients with Non-Small-Cell Lung Cancer and EGFR or ALK Alterations

Abstract

Contrary to Pemetrexed-containing chemo-immunotherapy studies, Atezolizumab, Bevacizumab, Carboplatin, and Paclitaxel (ABCP) treatment has consistently shown clinical benefit in prospective studies in patients with lung cancer and actionable mutations, where intracranial metastases are common. Here, we aimed to describe the real-life population of patients fit to receive ABCP after targeted therapy and quantify its clinical effect in patients with brain metastases. Patients treated in Cheshire and Merseyside between 2019 and 2022 were identified. Data were collected retrospectively. A total of 34 patients with actionable EGFR or ALK alterations had treatment with a median age of 59 years (range 32-77). The disease control rate was 100% in patients with PDL1 ≥ 1% (n = 10). In total, 19 patients (56%) had brain metastases before starting ABCP, 17 (50%) had untreated CNS disease, and 4 (22%) had PDL1 ≥ 1%. The median time to symptom improvement was 12.5 days (range 4-21 days), with 74% intracranial disease control rates and 89.5% synchronous intracranial (IC) and extracranial (EC) responses. IC median Progression Free Survival (mPFS) was 6.48 months, EC mPFS was 10.75 months, and median Overall Survival 11.47 months. ABCP in real-life patients with brain metastases (treated or untreated) was feasible and showed similar efficacy to that described in patients without actionable mutations treated with upfront chemo-immunotherapy.

Keywords: ALK; Atezolizumab; EGFR; PDL1; Paclitaxel; brain metastases; checkpoint inhibitor; immunotherapy; lung cancer.

Figure 1

Kaplan–Meyer curves for all 34 patients plotted with 95% confidence intervals (dotted lines). (A) Progression-Free Survival. (B) Overall Survival. Black squares in the coloured lines represent censored patients. mPFS; median Progression-Free Survival. mOS; median Overall Survival.

Figure 2

Response rates (A,C) and survival curves (B,D) of patients with known PDL1 expression (A,B), and of patients with EGFR mutation with or without T790M-acquired mutation (C,D). Black squares represent censored patients. PD; progressive disease, DCR; disease control rate, mOS; median Overall Survival.

Figure 3

Kaplan–Meyer curves for the 19 patients who had brain metastases before starting ABCP treatment plotted with 95% confidence intervals. (A) Intracranial Progression-Free Survival, (B) Extracranial Progression-Free Survival, and (C) Overall Survival. Black squares represent censored patients. Discontinuous lines mark 50% on the Y axis and the 12-month mark on the X axis. mPFS; median Progression-Free Survival. mOS; median Overall Survival.

Figure 4

Clinical outcomes of CNS patients plotted for individual patients and separated along the Y axis according to radiological response to ABCP. Combined PFS of previous TKI treatments are plotted on the left for each patient, with the number of TKI treatment lines within each bar. ABCP outcomes (OS from day 1 ABCP, extracranial PFS, and intracranial PFS) are plotted on the right. Patients with ALK translocations are marked as ALK+. mOS; median Overall Survival, mPFS; median Progression-Free Survival, IC; intracranial, EC; extracranial.