1433P - CNS efficacy of atezolizumab, bevacizumab, carboplatin and paclitaxel in patients with non-small cell lung cancer and actionable mutations

Background

Prospective and retrospective data support the use of Atezolizumab in combination with Bevacizumab, Carboplatin and Paclitaxel (ABCP) in patients with extensive non-small cell lung cancer with EGFR mutations after exhausting oral targeted therapy. The atezo-brain study showed CNS efficacy of upfront atezolizumab and platinum doublet in patients without EGFR or ALK alterations and untreated brain metastases (CNS mPFS 6.9 months). The clinical impact of ABCP in patients with brain metastases and EGFR or ALK alterations remains unknown. Here we aimed to quantify the clinical impact of ABCP in our patient population with actionable mutations and brain metastases.

Methods

Patients with actionable mutations and CNS disease treated at the Clatterbridge Cancer Centre with ABCP between 2019 and 2022 were identified. All patients had been consistently selected, monitored, and documented by the same team. Data was collected retrospectively. Progression-free survival (PFS) and Overall Survival (OS) were quantified from day 1 of cycle 1.

Results

19 patients had brain metastases at baseline, with an average age of 59 (range 32-77). 4 had ALK translocations, 2 had rare EGFR mutations and 13 had common EGFR mutations. 4 patients had received brain radiotherapy. 13 patients had asymptomatic brain metastases and 7 patients had well-controlled CNS symptoms. They all had an average of 11 cycles of treatment (median 7). Disease control was achieved in 14 patients (74%) with partial response in 9 of them (47%). There was a 94% concordance in intracranial vs extracranial response. All patients with CNS symptoms experienced a subjective improvement after an average of 13 days, although one patient was then noted to have CNS progression on brain MRI at week 9. The median PFS was 5.71 months (CNS mPFS 6.79 months) and the median OS was 11.21 months. Grade 3-4 toxicity leading to treatment modification occurred in 10 patients (53%), but none leading to treatment discontinuation.

Conclusions

Our data indicates CNS efficacy of ABCP regardless of the actionable mutation or previous CNS treatment, with frequent and quick responses. This supports the use of ABCP in patients with actionable mutations and untreated brain metastasis.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Clatterbridge Cancer Centre.

Funding

Has not received any funding.

Disclosure

C. Escriu: Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Invited Speaker: Roche. All other authors have declared no conflicts of interest.