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

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.

The impact of an educational and information systems initiative on somatic BRCA testing rates in patients with high grade serous tubo-ovarian cancer in Western Australia.

Objective: Poly-ADP ribose polymerase inhibitors (PARPi) have expanded the management armamentarium against high grade serous tubo-ovarian cancer (HGSOC) in patients with germline and somatic BRCA pathogenic variants (PVs). Germline testing has been available in Western Australia (WA) since July 2015, whilst somatic BRCA testing was previously only available through interstate laboratories. We hypothesized that due to complexity of referral, testing rates for somatic BRCA would be low. We aimed to demonstrate that improving education and information systems would improve testing rates in our service. Methods: Retrospective data were collected for all patients with HGSOC reviewed between June - November 2021. BRCA testing for this period was discussed at multi-disciplinary tumor board. Patients eligible to commence PARPi that had not received somatic testing were referred. Changes were implemented to patient outcome reports, the results application was adjusted to flag clinicians, departmental guidelines were developed, and teaching sessions conducted. Testing rates from March - August 2022 were compared. Results: From June - November 2021, 98% of patients had germline BRCA testing performed. PVs in BRCA1/2 were detected in 18% of patients. Of those without germline PVs, further somatic BRCA testing was referred in 42% of patients. One somatic PV was detected. From March - August 2022, 99% of patients had germline BRCA testing and 17% had PVs detected. Further somatic BRCA testing was referred in 72% of patients. No somatic PVs were detected. Conclusion: Testing rates for germline BRCA variants in patients with HGSOC in WA are high. Focused education and information systems improved somatic BRCA testing rates.