Abstract 305P
Background
Anti-PDL1 associated with platinum based chemotherapy (CT) is the standard of care for esSCLC. Liver metastases (LM) promote immune tolerance and induce resistance to immunotherapy. In this study, we explored the prognostic and predictive roles of LM on the efficacy of anti-PDL1 in addition to upfront CT in esSCLC.
Methods
Patients (pts) included in the phase III CASPIAN (discovery cohort) and IMpower133 (validation cohort) trials were included. Both trials randomized pts between CT alone or in combination with: durvalumab (D-CT) or durvalumab tremelimumab (DT-CT) for the CASPIAN study, atezolizumab (A-CT) for IMpower133. Multivariable (MV) Cox models were constructed to assess the prognostic value of LM. Predictive value of LM was explored with an interaction term.
Results
In the discovery cohort, 782 pts were included, of whom 320 had LM. 258 pts received CT, 264 D-CT and 260 DT-CT. LM were associated with poor PFS (m 4.7 months vs 6.3 mo, p < 0.0001) and OS (m 8.6 mo vs 13.9 mo, p < 0.0001), regardless treatment arm. LM was predictive of the absence of immunotherapy benefit with non-significant HR for PFS and OS for the D-CT and DT-CT arms (p for interaction: 0.03 for PFS, 0.32 for OS) unlike LM- pts (Table). In the validation cohort, 393 pts were included, of whom 144 had LM. 198 pts received A-CT and 195 CT. Similarly to the discovery cohort, LM were a poor prognostic factor for PFS (m 4.2 mo vs 5.4 mo, p < 0.0001) and OS (m 8.6 mo vs 12.5 mo, p < 0.0001), regardless treatment arm. Anti PDL1 showed less benefit in PFS and OS compared to the LM- population, despite non-significant p for interaction: 0.77 for OS and 0.52 for PFS (Table).
Table 305P| Progression free survival | Overall survival | |||||||
| LM+ | LM– | LM+ | LM– | |||||
| HR* (95%CI) | p | HR* (95%CI) | p | HR* (95%CI) | p | HR* (95%CI) | p | |
| CASPIAN | ||||||||
| CT | − | − | − | |||||
| D-CT | 1.13 | 0.70 | 0.69 | 0.01 | 1.02 | 0.89 | 0.69 | 0.02 |
| (0.84–1.52) | (0.54–0.89) | (0.75–1.38) | (0.53–0.91) | |||||
| DT-CT | 1.03 (0.77–1.39) | 0.76 (0.59–0.98) | 0.95 (0.70–1.29) | 0.80 (0.61–1.05) | ||||
| IMpower133 | ||||||||
| CT | − | − | − | − | ||||
| A-CT | 0.75 (0.52–1.08) | 0.12 | 0.67 (0.51–0.87) | 0.003 | 0.73 (0.51–1.07) | 0.11 | 0.71 (0.52–0.98) | 0.04 |
*All HR are multivariate, adjusted on prognostic factors selected in the univariate analysis.
Conclusions
LM are associated with poor prognostic in pts with esSCLC treated with first line anti-PDL1 plus CT. LM might be a predictive marker for anti PDL1 inefficiency. Novel treatment strategies should be explored for this population.
Clinical trial identification
NCT03043872, NCT02763579.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
E. Auclin: Financial Interests, Personal, Advisory Board: Amgen, Sanofi; Non-Financial Interests, Personal, Other: Ipsen, BMS; Financial Interests, Institutional, Research Grant: Ipsen. L. Mezquita: Financial Interests, Personal, Training: BMS, AstraZeneca, Roche, Takeda, Janssen, Pfizer, MSD; Financial Interests, Personal, Advisory Role: Roche, Takeda, Janssen, MSD; Financial Interests, Personal, Research Grant: Inivita, AstraZeneca, Gilead. S. Cousin: Financial Interests, Personal, Advisory Board: AbbVie, Amgen, Lilly, Roche; Non-Financial Interests, Personal, Principal Investigator: AstraZeneca, Daiichi Sankyo, Gilead, Takeda, Sanofi, MSD, GSK, BMS. B. Besse: Financial Interests, Institutional, Advisory Board: AbbVie, BioNTech SE, Beijing Aviston Biotechnology, Bristol Myers Squibb, CureVac AG, PharmaMar, Sanofi Aventis, Regeneron; Financial Interests, Institutional, Expert Testimony: AbbVie, Bristol Myers Squibb, Eli Lilly, Ellipse pharma Ltd, CureVac AG, F. Hoffmann-La Roche Ltd, Foghorn Therapeutics Inc., Genmab, Immunocore, Owkin, Sanofi; Financial Interests, Institutional, Invited Speaker: AbbVie, AstraZeneca, Bristol Myers Squibb, MSD, Daiichi Sankyo, Eli Lilly, Ose Immunotherapeutics, Sanofi, Servier, Ose immunotherapeutics, Sanofi, Takeda, Genmab, Taiho, AstraZeneca, Amgen, BeiGene, CureVac, Janssen, MSD, PharmaMar, Eli Lilly, Daiichi Sankyo, Enliven, Nuvalent, Ellipsis, Prelude Therapeutics; Non-Financial Interests, Personal, Leadership Role, Chair of the Scientific Chairs Council: EORTC; Non-Financial Interests, Personal, Advisory Role, Member of the Scientific Board: IFCT. All other authors have declared no conflicts of interest.