347P - Real-world efficacy of first-line therapy in wild-type non-small cell lung cancer (NSCLC) patients with brain metastases

Background

De novo brain metastases occur frequently in NSCLC. Untreated brain metastases are an exclusion criteria for most clinical trials whilst local therapies administered at the time of diagnosis may confound radiological response assessment. The intracranial activity of first line chemoimmunotherapy in this setting is uncertain, therefore further data on optimal treatment sequencing are needed.

Methods

Patients with wild-type NSCLC and de novo brain metastases receiving 1^st line chemoimmunotherapy or single agent immunotherapy were selected from clinical databases from three institutions. A composite time-to event (TTE) outcome of intracranial disease progression, death or need for local therapy to brain metastases was calculated as a surrogate for intracranial disease progression.

Results

A total of 68 patients were included. Patients were predominantly male (59%), 1 (61%) or 0 (28%), symptomatic (50%) with an adenocarcinoma (90%). The PD-L1 TPS was <1% (37%), 1-49% (17%) and >50% (46%) respectively. Surgery (26%) or upfront radiotherapy (43%) were performed prior to systemic therapy, with 45% proceeding to upfront systemic therapy alone (best intracranial response CR 2/68, PR 8/68, SD 10/68, PD 2/68, NE 9/68). Sixty-nine percent of patients received chemoimmunotherapy and 31% single agent pembrolizumab. At a median follow-up of 20.7 months, OS was 15 months and the median intracranial TTE was 7.3 months. Subgroup analysis did not reveal any significant difference in TTE when patients were stratified according to the presence of brain metastasis symptoms, number of brain metastases or TPS, despite a trend towards significance (p=0.1) in patients who received radiotherapy.

Conclusions

These data suggest that clinical prognostic factors such as PD-L1 status, number of brain metastases or symptoms at baseline are not predictive of intracranial response to chemoimmunotherapy or immunotherapy alone, however the trend towards improved TTE with upfront local treatment may identify patients in whom this treatment sequence is optimal. This warrants further investigation in a larger patient cohort or a prospective trial of treatment sequence.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

M. Itchins: Financial Interests, Personal, Advisory Board: Roche, MSD. M. Boyer: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Role: MSD, AstraZeneca, Bristol Myers Squibb, Janssen; Financial Interests, Personal, Research Grant: MSD, Pfizer, Boehringer Ingelheim, Lilly, Roche, AstraZeneca, Bristol Myers Squibb, Amgen, Ascentage Pharma, Novartis, Merck Serono; Financial Interests, Personal, Sponsor/Funding: MSD, Genentech/Roche. N. Pavlakis: Financial Interests, Personal, Advisory Board: Boehringer Ingelheim, MSD, Merck, BMS, AstraZeneca, Takeda, Pfizer, Roche, Amgen, BeiGene, Novartis, AllVascular; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim, Pfizer, Roche, Takeda, Pierre-Fabre; Financial Interests, Institutional, Funding: Bayer, Pfizer, Roche. S.C. Kao: Financial Interests, Personal, Advisory Board: Roche, MSD. All other authors have declared no conflicts of interest.