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

BackgroundSeminal 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.MethodsRetrospective 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.Results71 patients from six centres, median age 66.0years, 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 tumour 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=0.013). 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% (OR3.46, p=0.06), without complete response (OR5.06, p=0.04), and with treated oligoprogression (OR3.11, p=0.05). 36-month landmark survival was 98.2%.ConclusionPatients 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.Micro Abstract• Seminal trials with first-line pembrolizumab for metastatic non-small cell lung cancer (NSCLC) mandated a maximum two years treatment. We present real world outcomes of a multi-site Australian cohort of patients who completed two years of treatment.• Retrospective data were collected from the AURORA (AUstralian Registry and biObank of thoRacic cAncers) national database. Primary endpoints were progression rate post pembrolizumab discontinuation and progression free survival (PFS).• 71 patients were identified. Many past (66%) or current (24%) smokers with mean 37 pack-years. Median PD-L1 tumour proportion score (TPS) was 68% with high rates of KRAS mutation (60%).• Post pembrolizumab discontinuation 20 patients (28%) had disease progression. Median PFS was 46.1 months (95%CI 39.5-NR). A significant proportion of patients had brain metastases at diagnosis and treated oligoprogression during pembrolizumab and still completed two years of therapy.• Progression rate after pembrolizumab cessation was higher in PD-L1 negative patients and in those without complete response.