1450P - Addition of bevacizumab to first-line chemoimmunotherapy in NSCLC with liver metastases

Background

Liver metastases create a unique immunosuppressive microenvironment in patients with advanced non-small cell lung cancer (aNSCLC) and are associated with poorer outcomes when treated with chemoimmunotherapy, especially in non-squamous (ns-) aNSCLC.

Methods

We retrospectively analyzed data from IMpower150 and IMpower130, which included patients with ns-aNSCLC without EGFR/ALK/KRAS alterations, treated with first-line chemotherapy (CT) with/out atezolizumab (CT+IT) and/or bevacizumab (CT+IT+AA, CT+AA). Data was available on the VIVLI platform.

Results

Out of the 1,523 evaluable patients, 20.4% (n=311), 46.4% (n=707), 19.7% (n=300), and 13.4% (n=205) received CT+IT+AA, CT+IT, CT+AA, and CT, respectively. 13.9% (n=212) of the patients had liver metastases (LM). LM were associated with lower serum albumin and higher lactate dehydrogenase levels, a greater number of metastatic sites (all p<0.001) and poor outcomes across all treatment regimens except for patients treated with upfront CT+IT+AA (Table). In the overall population, CT+IT+AA achieved longer progression-free survival (HR for PFS: 0.74, p<0.001) but not overall survival (HR for OS: 0.91, p=0.38) compared to CT+IT. Of all included variables (age, smoking status, Lung Immune Prognostic Index (LIPI), albumin levels, ECOG performance status, and number of metastatic sites), only LM+ patients yielded substantial OS benefit of CT+IT+AA vs. CT+IT (HR for PFS: 0.44, p<0.001; HR for OS: 0.43, p=0.002, Table). No benefit of CT+AA over CT in patients with/out LM was observed. Table: 1450P

Impact of liver metastases on PFS and OS across all regimens and on response to CT+IT +/- AA

Conclusions

LM are associated with poor outcomes in patients with aNSCLC treated with CT, CT+AA and CT+IT but not CT+IT+AA. The addition of bevacizumab to CT+IT improves outcomes (PFS and OS) in patients with liver metastases and helps correct its negative prognostic impact. The presence of liver metastasis may help in guiding treatment selection in first-line aNSCLC.

Clinical trial identification

Impower130: NCT02367781; Impower150: NCT02366143.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

S. Oudard: Financial Interests, Personal, Advisory Role: AstraZeneca, Astellas, Bayer, BMS, Ipsen, Janssen, Merck, MSD, Novartis, Pfizer, Sanofi; Financial Interests, Personal, Non financial benefits, Travel Accomodations and Expenses: Eisai, Roche; Financial Interests, Personal, Advisory Board: Roche. C. Thibault: Financial Interests, Personal, Advisory Board: Janssen, Astellas, Sanofi, Ipsen, Pfizer, Merck, MSD, BMS, AstraZeneca, AAA, Seagen; Financial Interests, Institutional, Funding: AstraZeneca, Sanofi. V.M. Albarran Artahona: Financial Interests, Invited Speaker: Merck; Financial Interests, Non financial benefits, Travel, accomodations, expenses: Janssen. C. Teixido: Financial Interests, Personal, Invited Speaker: AstraZeneca, Merck Sharp & Dohme, Roche Farma, Diaceutics, Pfizer, Janssen Oncology; Financial Interests, Personal, Advisory Board: AstraZeneca, Novartis; Financial Interests, Institutional, Research Grant: Novartis. B. Besse: Financial Interests, Institutional, Funding: 4D Pharma, AbbVie, Amgen, Aptitude Health, AstraZeneca, BeiGene, Blueprint Medicines, Boehringer Ingelheim, Celgene, Cergentis, Cristal Therapeutics, Daiichi Sankyo, Eli Lilly, GSK, Janssen, Onxeo, Ose Immunotherapeutics, Pfizer, Roche-Genentech, Sanofi, Takeda, Tolero Pharmaceuticals; Financial Interests, Institutional, Research Grant: Genzyme Corporation, Chugai Pharmaceutical, Eisai, Inivata, Ipsen, Turning Point Therapeutics. L. Mezquita: Financial Interests, Personal, Advisory Board: Takeda, AstraZeneca, Roche; Financial Interests, Personal, Invited Speaker: Roche, BMS, AstraZeneca, Takeda; Financial Interests, Personal, Research Grant, SEOM Beca Retorno 2019 : BI; Financial Interests, Personal, Research Grant, ESMO TR Research Fellowship 2019 : BMS; Financial Interests, Institutional, Research Grant, COVID research Grant: Amgen; Financial Interests, Institutional, Coordinating PI: INIVATA, Stilla. E. Auclin: Financial Interests, Advisory Board: Sanofi, Amgen. All other authors have declared no conflicts of interest.