Longitudinal Study of Advanced Non-Small Cell Lung Cancer with Initial Durable Clinical Benefit to Immunotherapy: Strategies for Anti-PD-1/PD-L1 Continuation beyond Progression

Ivan Pourmir; Reza Elaidi; Zineb Maaradji; Hortense De Saint Basile; Monivann Ung; Mohammed Ismaili; Laure Fournier; Bastien Rance; Laure Gibault; Rym Ben Dhiab; Benoit Gazeau; Elizabeth Fabre

doi:10.3390/cancers15235587

Longitudinal Study of Advanced Non-Small Cell Lung Cancer with Initial Durable Clinical Benefit to Immunotherapy: Strategies for Anti-PD-1/PD-L1 Continuation beyond Progression

Cancers (Basel). 2023 Nov 26;15(23):5587. doi: 10.3390/cancers15235587.

Authors

Affiliations

¹ Department of Thoracic Oncology, Georges Pompidou European Hospital, CARPEM, Paris Cité University, 20 Rue Leblanc, 75015 Paris, France.
² INSERM U970, Université Paris-Cité, 56 Rue Leblanc, 75015 Paris, France.
³ Department of Radiology, Georges Pompidou European Hospital, CARPEM, AP-HP Paris Cité University, 20 Rue Leblanc, 75015 Paris, France.
⁴ Department of Medical Bioinformatics, Georges Pompidou European Hospital, 20 Rue Leblanc, 75015 Paris, France.
⁵ Department of Pathology, Georges Pompidou European Hospital, AP-HP, Cité University, 20 Rue Leblanc, 75015 Paris, France.

Abstract

Background and aim: A better understanding of resistance to checkpoint inhibitors is essential to define subsequent treatments in advanced non-small cell lung cancer. By characterizing clinical and radiological features of progression after anti-programmed death-1/programmed death ligand-1 (anti-PD-1/PD-L1), we aimed to define therapeutic strategies in patients with initial durable clinical benefit.

Patients and methods: This monocentric, retrospective study included patients who presented progressive disease (PD) according to RECIST 1.1 criteria after anti-PD-1/PD-L1 monotherapy. Patients were classified into two groups, "primary resistance" and "Progressive Disease (PD) after Durable Clinical Benefit (DCB)", according to the Society of Immunotherapy of Cancer classification. We compared the post-progression survival (PPS) of both groups and analyzed the patterns of progression. An exploratory analysis was performed using the tumor growth rate (TGR) to assess the global growth kinetics of cancer and the persistent benefit of immunotherapy beyond PD after DCB.

Results: A total of 148 patients were included; 105 of them presented "primary resistance" and 43 "PD after DCB". The median PPS was 5.2 months (95% CI: 2.6-6.5) for primary resistance (p < 0.0001) vs. 21.3 months (95% CI: 18.5-36.3) for "PD after DCB", and the multivariable hazard ratio was 0.14 (95% CI: 0.07-0.30). The oligoprogression pattern was frequent in the "PD after DCB" group (76.7%) and occurred mostly in pre-existing lesions (72.1%). TGR deceleration suggested a persistent benefit of PD-1/PD-L1 blockade in 44.2% of cases.

Conclusions: PD after DCB is an independent factor of longer post-progression survival with specific patterns that prompt to contemplate loco-regional treatments. TGR is a promising tool to assess the residual benefit of immunotherapy and justify the continuation of immunotherapy in addition to radiotherapy or surgery.

Keywords: PD-1; acquired resistance; immune checkpoint inhibitors; non-small cell lung cancer; oligoprogression; tumor growth rate.

Grants and funding

This research received no external funding.