Completion of Pembrolizumab in Advanced Non-Small Cell Lung Cancer-Real World Outcomes After Two Years of Therapy (COPILOT)

Andrew Fantoni; Lydia Warburton; Benjamin Solomon; Marliese Alexander; Meghana Maddula; Lauren Julia Brown; Ines Pires da Silva; Adnan Nagrial; Farah Abu Al-Hial; Malinda Itchins; Nick Pavlakis; Samantha Bowyer

doi:10.1016/j.cllc.2024.04.008

Completion of Pembrolizumab in Advanced Non-Small Cell Lung Cancer-Real World Outcomes After Two Years of Therapy (COPILOT)

Clin Lung Cancer. 2024 Jul;25(5):449-459. doi: 10.1016/j.cllc.2024.04.008. Epub 2024 Apr 15.

Authors

Affiliations

¹ Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia; Fiona Stanley Hospital, Murdoch, Western Australia, Australia. Electronic address: [email protected].
² Fiona Stanley Hospital, Murdoch, Western Australia, Australia; Edith Cowan University, Joondalup, Western Australia, Australia.
³ Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia.
⁴ Blacktown Hospital, Blacktown, New South Wales, Australia; Westmead Hospital, Westmead, New South Wales, Australia.
⁵ Blacktown Hospital, Blacktown, New South Wales, Australia; Westmead Hospital, Westmead, New South Wales, Australia; Westmead Institute for Medical Research, Westmead, New South Wales, Australia; The University of Sydney, Sydney, New South Wales, Australia.
⁶ Blacktown Hospital, Blacktown, New South Wales, Australia; The University of Sydney, Sydney, New South Wales, Australia; Melanoma Institute of Australia, Wollstonecraft, New South Wales, Australia.
⁷ Blacktown Hospital, Blacktown, New South Wales, Australia; Westmead Hospital, Westmead, New South Wales, Australia; The University of Sydney, Sydney, New South Wales, Australia.
⁸ Royal North Shore Hospital, St Leonards, New South Wales, Australia.
⁹ The University of Sydney, Sydney, New South Wales, Australia; Royal North Shore Hospital, St Leonards, New South Wales, Australia; GenesisCare St Leonards, St Leonards, New South Wales, Australia.
¹⁰ Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia; University of Western Australia, Crawley, Western Australia, Australia.

PMID: 38705835
DOI: 10.1016/j.cllc.2024.04.008

Abstract

Background: Seminal trials with first-line pembrolizumab for metastatic non-small cell lung cancer (NSCLC) mandated a maximum two-years treatment. We describe real-world outcomes of a multi-site Australian cohort of patients who completed two-years of pembrolizumab.

Methods: Retrospective data were collected from the national AUstralian Registry and biObank of thoRacic cAncers (AURORA). Primary endpoints were progression rate post pembrolizumab discontinuation; and progression free survival (PFS). Local treatment of oligoprogressive disease during pembrolizumab was allowed.

Results: A total of 71 patients from six centers, median age 66.0 years, 49% male and 90% ECOG ≤ 1 were identified. Patients were Caucasian (82%) or Asian (16%); past (66%) or current (24%) smokers with mean 37 pack-years. Histology comprised 73% adenocarcinoma and 16% squamous. 18 patients (25%) had brain metastases at diagnosis. Median PD-L1 tumor proportion score (TPS) was 68%; 12 patients (17%) TPS < 1% and 43 (61%) TPS ≥ 50%. No patients had EGFR/ALK/ROS1 alterations; 29/49 tested (60%) had KRAS mutations. Median follow up was 38.7 months. Objective response rate 78.6%. Median PFS 46.1 months (95% CI 39.5-NR), not reached (46.1-NR) in PD-L1 TPS ≥ 1% versus 28.1 months (16.3-NR) in TPS < 1% (P = .013). 17 patients (24%) received additional local therapy for oligoprogression. Post pembrolizumab discontinuation, 20 patients (28%) had disease progression. Higher rates of progression occurred with TPS < 1% (OR 3.46, P = .06), without complete response (OR 5.06, P = .04), and with treated oligoprogression (OR 3.11, P = .05). 36-month landmark survival was 98.2%.

Conclusion: Patients completing two-years of pembrolizumab for NSCLC in an Australian cohort had high rates of KRAS mutation and PD-L1 expression; a proportion had brain metastases and treated oligoprogression. Progression post pembrolizumab was higher in PD-L1 TPS < 1% and in those without complete response.

Keywords: Australia; Immunotherapy; NSCLC; PD-1 inhibitors; Real world data.

Publication types

Multicenter Study

MeSH terms

Adult
Aged
Aged, 80 and over
Antibodies, Monoclonal, Humanized* / therapeutic use
Antineoplastic Agents, Immunological* / therapeutic use
Australia
Carcinoma, Non-Small-Cell Lung* / drug therapy
Carcinoma, Non-Small-Cell Lung* / mortality
Carcinoma, Non-Small-Cell Lung* / pathology
Female
Follow-Up Studies
Humans
Lung Neoplasms* / drug therapy
Lung Neoplasms* / mortality
Lung Neoplasms* / pathology
Male
Middle Aged
Retrospective Studies
Survival Rate
Treatment Outcome

Substances

pembrolizumab
Antibodies, Monoclonal, Humanized
Antineoplastic Agents, Immunological