Abstract 1150P
Background
Immunotherapy blocking the PD-1/PD-L1 axis has been used as monotherapy for barely a decade in advanced non-small cell lung cancers (aNSCLC). Tumor progression can occur even after durable clinical benefit (DCB), defined as a minimum of 6 month of responsive/stable disease (per RECIST 1.1). It is qualified as oligo-progression (OPD) if occurring in ≤3 lesions. Clinical and radiological data in this situation is still scarce and heterogeneous, but needed to optimize care and understand the underlying biological processes.
Methods
We reviewed clinical and radiological data of all aNSCLC cases which started an anti-PD-1/PD-L1 monotherapy between 2015-06-30 and 2019-10-31 in our single institution and had progressive disease (PD) after DCB. Disease was assed per RECIST 1.1, tumor growth rate (TGR) was calculated at baseline of immunotherapy and at first PD. Primary objective was to estimate the association of OPD with post-progression survival (PPS). Secondary objectives were radiological and TGR characterizations. Hazard ratios (HR, 95% CI) were obtained using multivariable Cox regression.
Results
Of 61 aNSCLC patients achieving DCB, 43 (70.5%) had subsequent PD and met our inclusion criteria. Median post-progression survival (PPS) was 21.3 months. PD occurred mostly as OPD (n=33, i.e. 76.2% of evaluable patients) and often limited to pre-existing lesions (72.1% of cases). 24/28 (85.7%) of assessable OPD had no lesions appearing at next imagery. Main sites of PD were lungs (44.2%), lymph nodes (34.9%) and central nervous system (11.6%). OPD was associated with an increased PPS, HR=0.18 (0.03-1.17) for death. TGR was assessable for 30/43 patients and suggested a persistent benefit of PD-1/PD-L1 blockade continuation beyond PD in at least 19/43 (44.2%) cases.
Conclusions
This study provides a rationale to guide clinical management and basic research on acquired resistance to immunotherapy. Overall, progression after DCB under PD-1/PD-L1 blockade appears in a few pre-existing lesions rather than new ones. OPD was associated with extended PPS. TGR is a promising tool for PD-1/PD-L1 blockade continuation decision.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
E. Fabre-Guillevin: Financial Interests, Institutional, Invited Speaker: Bristol Myers Squibb; Financial Interests, Institutional, Principal Investigator: Merck. All other authors have declared no conflicts of interest.