Thomas A. Burke

Background: Although data on patients treated with pembrolizumab are available from clinical trials and single-country real-world reports, to our knowledge no multi-country real-world studies have investigated the use of pembrolizumab as an adjuvant treatment for stage III melanoma. Methods: We used the European Melanoma Registry (EUMelaReg), a disease entity-based registry specific for melanoma, to examine treatment and outcomes for adult patients with stage III melanoma with lymph node involvement who had complete resection and received adjuvant treatment with pembrolizumab. The primary objectives were to describe the demographic and clinical characteristics of the included patients as well as time on adjuvant pembrolizumab treatment (TOT), real-world recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) from adjuvant pembrolizumab initiation. Secondary objectives were time to next treatment (TTNT) after adjuvant use of pembrolizumab, next-line therapy for stage III and unresectable stage IV melanoma and overall survival (OS) from initiation of pembrolizumab. Results: Patients were stratified according to age, sex, BRAF status, number of positive lymph nodes and disease substage. Median TOT was 11.1 (9.2–11.5) months, median RFS was 29.6 [18.7–not reached (NR)] months and median DMFS was 32.4 (22.7–NR) months. TTNT was 29.9 (22.2–NR) months, while median OS was not reached. Conclusions: The results of this study offer insights into the real-world use of pembrolizumab as an adjuvant therapy for melanoma in Europe.

Background: This study provides insights into the treatment use and outcomes of metastatic non-small cell lung cancer (NSCLC) patients in a real-world setting prior to and after the availability of immuno-oncology (IO) regimens in the first line (1L). Methods: Metastatic NSCLC patients, who initiated systemic 1L anticancer treatment from 2014 to 2020, were identified from health records. Patients were grouped into Pre-1L IO and Post-1L IO, according to the availability of pembrolizumab 1L monotherapy at the date of initiating 1L systemic anticancer treatment. Patient characteristics, treatment patterns and outcomes were assessed by the cohort. Overall survival (OS) and real-world progression-free survival (rwPFS) were calculated using the Kaplan-Meier method. Results: The most common 1L treatment was platinum-based chemotherapy regimens in both groups (≥46%), followed by single-agent chemotherapy (27.0%) in Pre-1L IO and pembrolizumab (26.0%) in Post-1L IO. Median OS was 6.2 (95% CI 5.5–7.4) in Pre- and 8.9 months (95% CI 7.5–10.6) in Post-1L IO, while rwPFS was 3.7 (95% CI 3.3–4.2) and 4.7 months (95% CI 3.9–5.7), respectively. Conclusions: Even if a small proportion of patients received a 1L IO, the data showed an improved survival outcomes in the Post-1L IO group.

The aims of this study were to describe systemic treatment patterns and clinical outcomes for unresectable advanced/metastatic non-small-cell lung cancer (NSCLC) by first-line regimen type in real-world clinical settings in Japan after the introduction of first-line immune checkpoint inhibitor (ICI) monotherapy in 2017. Using retrospective chart review at 23 study sites, we identified patients ≥20 years old initiating first-line systemic therapy from 1 July 2017 to 20 December 2018, for unresectable stage IIIB/C or IV NSCLC; the data cutoff was 30 September 2019. Eligible patients had recorded programmed death-ligand 1 (PD-L1) tumor proportion score (TPS) and no known actionable EGFR/ALK/ROS1/BRAF genomic alteration. Kaplan-Meier method was used to determine time-to-event endpoints. Of 1208 patients, 647 patients (54%) received platinum doublet, 463 (38%) received ICI monotherapy, and 98 (8%) received nonplatinum cytotoxic regimen as first-line therapy. PD-L1 TPS was ≥50%, 1–49% and <1% for 44%, 30%, and 25% of patients, respectively. Most patients with PD-L1 TPS ≥50% received ICI monotherapy (453/529; 86%). Excluding 26 patients with ECOG performance status of 3–4 from outcome analyses, the median patient follow-up was 11.3 months. With first-line platinum doublet, ICI monotherapy, and nonplatinum cytotoxic regimens, median overall survival (OS) was 16.3 months (95% CI, 14.0–20.1 months), not reached, and 14.4 months (95% CI, 10.3–21.2 months), respectively; 24-month OS was 40%, 58%, and 31%, respectively. Differences in OS relative to historical cohort data reported in Japan are consistent with improvement over time in real-world clinical outcomes for advanced NSCLC.

Our aim was to evaluate real-world time on treatment (rwToT), overall and by KRAS mutation status, with first-line pembrolizumab monotherapy for advanced non-small cell lung cancer (NSCLC) in real-world oncology practice in the US. rwToT is a readily available, intermediate-range endpoint that is moderately to highly correlated with overall survival in clinical trials and real-world data. Using deidentified electronic medical record data, we studied patients with ECOG performance status (PS) of 0–2 who initiated pembrolizumab (1 November 2016 to 31 March 2020) for advanced NSCLC with programmed death-ligand 1 (PD-L1) expression ≥ 50% and without EGFR/ALK/ROS1 genomic alterations. The data cutoff was 31 March 2021, and the median study follow-up was 34 months. The Kaplan–Meier median rwToT with first-line pembrolizumab monotherapy was 7.4 months (95% CI, 6.3–8.1) for 807 patients with PS 0–1, which was consistent with the median treatment duration in the KEYNOTE-024 trial (7.9 months). The median rwToT for 237 patients with PS 2 was 2.1 months (95% CI, 1.4–2.8). For those with KRAS-mutated and KRAS wild-type nonsquamous NSCLC and PS 0–1, the median rwToT was 7.6 months and 7.0 months, respectively. Our findings suggest long-term benefit of first-line pembrolizumab monotherapy for advanced NSCLC with PD-L1 expression ≥ 50% in real-world settings in the US, particularly for patients with good performance status at the start of therapy, irrespective of KRAS status.

Background Pembrolizumab monotherapy and nivolumab in combination with ipilimumab are US FDA-approved first-line (1L) regimens for patients with metastatic non-small cell lung cancer (NSCLC) without epidermal growth factor receptor or anaplastic lymphoma kinase genomic aberrations and with a programmed death ligand 1 (PD-L1) tumor proportion score (TPS) of >= 1%. A published matching-adjusted indirect comparison found the two regimens yield comparable overall and progression-free survival outcomes. Objective The aim of this study was to compare direct medical costs of pembrolizumab and nivolumab plus ipilimumab for PD-L1-positive metastatic NSCLC treatment within the first 3 years following treatment initiation from a US payer perspective. Methods A cost-minimization model was built to estimate and compare treatment, disease management, and adverse event costs based on KEYNOTE-024 and -042, and CheckMate 227 Part 1a trial survival and adverse event data. Results 1L pembrolizumab generates $54,343, $75,744, and $76,259 per patient cost savings compared with 1L nivolumab plus ipilimumab for patients with NSCLC with PD-L1 TPS >= 1% within 1, 2, and 3 years of treatment initiation, respectively. Conclusion Pembrolizumab is cost saving as 1L treatment for PD-L1-positive metastatic NSCLC in comparison with nivolumab plus ipilimumab, at least for the short term.

Background: In the absence of head-to-head trials, this study indirectly compared the effectiveness of pembrolizumab + chemotherapy vs nivolumab + ipilimumab for the first-line treatment of metastatic stage IV NSCLC patients with PD-L1 tumor proportion score (TPS) ≥1%. Methods: An anchored matching-adjusted indirect comparison (MAIC) was conducted using pooled individual patient data (IPD) from the ITT population in KEYNOTE-021G, KEYNOTE-189 and KEYNOTE-407 (n = 816) and published aggregate data of nivolumab + ipilimumab from CheckMate 227 Part 1A (n = 793). To adjust for cross-trial differences in baseline characteristics, data from KEYNOTE-021G/KEYNOTE-189/KEYNOTE-407 were re-weighted to match the baseline characteristics of CheckMate 227 Part 1A. Outcomes included OS, PFS and ORR. Base case analyses were restricted to patients with PD-L1 TPS ≥1%, with sub-group analyses in PD-L1 TPS ≥50% and 1–49%. Results: The estimated HR (95% CI) of pembrolizumab + chemotherapy vs nivolumab + ipilimumab was 0.80 (0.59,1.09) and 0.53 (0.41,0.68) for OS and PFS, respectively. For ORR, the estimated risk ratio was 1.8 (1.3,2.4) for pembrolizumab + chemotherapy vs nivolumab + ipilimumab and the risk difference was 25.5% (15.0,36.0). PD-L1 TPS ≥50% and 1–49% sub-groups showed an OS HR of 0.89 (0.58,1.36) and 0.68 (0.46,1.01), respectively. Conclusion: These MAIC results suggest that pembrolizumab + chemotherapy leads to a greater clinical benefit vs nivolumab + ipilimumab in patients with PD-L1 TPS ≥1% across multiple endpoints.

Objectives Our objectives were to evaluate the cost effectiveness of pembrolizumab compared with standard-of-care (SoC) platinum-based chemotherapy as first-line treatment in patients with metastatic non-small-cell lung cancer (NSCLC) that expresses high levels of programmed death ligand-1 (PD-L1) [tumour proportion score (TPS) ≥50%], from a US third-party public healthcare payer perspective. Methods We conducted a partitioned-survival model with a cycle length of 1 week and a base-case time horizon of 20 years. Parametric models were fitted to Kaplan–Meier estimates of time on treatment, progression-free survival and overall survival from the KEYNOTE-024 randomized clinical trial (patients aged ≥18 years with stage IV NSCLC, TPS ≥50%, without epidermal growth factor receptor (EGFR)-activating mutations or anaplastic lymphoma kinase (ALK) translocations who received no prior systemic chemotherapy) and validated with long-term registry data. Quality-adjusted life-years (QALYs) were calculated based on EuroQoL-5 Dimensions (EQ-5D) utility data collected in the trial. Costs ($US, year 2016 values) for drug acquisition/administration, adverse events and clinical management were included. Costs and outcomes were discounted at 3% per year. A series of deterministic and probabilistic sensitivity analyses were performed to test the robustness of the results. Results In the base-case scenario, pembrolizumab resulted in an expected gain of 1.31 life-years (LYs) and 1.05 QALYs and an incremental cost of $US102,439 compared with SoC. The incremental cost per QALY gain was $US97,621/QALY and the incremental cost per LY gain was $US78,344/LY. Conclusions Pembrolizumab is projected to be a cost-effective option compared with SoC platinum-based chemotherapy as first-line treatment in adults with metastatic NSCLC expressing high levels of PD-L1.

E20577 Background: The treatment landscape for advanced/metastatic NSCLC has changed with new targeted therapies & use of companion diagnostics. Methods: The objective of this retrospective chart review study was to describe the treatment, biopsy, BMx practice patterns & HCRU in Australian & Korean, newly diagnosed Stage IIIB/IV NSCLC patients who initiated first line therapy (1LT) during Jan/1/2011-July/1/2013. Data were analyzed descriptively. Overall survival (OS) from start of 1LT & second line therapy (2LT) was estimated using Kaplan-Meier method. Results: In 210 Australian patients, 12% were never smokers & 77.6% had non-squamous histology (NSH). 62% (n = 130) received 2LT, 26% (n = 55) received 3L+ treatment (3L+T). The top three 1LT were carboplatin+gemcitabine (n = 112, 53%), carboplatin+paclitaxel (n = 19, 9%), cisplatin+etoposide (n = 10, 5%). 59% (n = 77) of patients received single agent 2LT, 49% of non-squamous patients (NSP) received pemetrexed (n = 50), 29% of squamous patients (SP) received docetaxel (n = 4). 95% of patients (n = 200) had a biopsy performed. Of 163 NSP, 72% (n = 117) received BMx. 98% (n = 115) received an EGFR test, 23% (n = 27) of which were positive. Median OS from start of 1LT & 2LT was 11.6 & 7.9 months respectively. In 150 Korean patients, 34% (n = 51) were never smokers & 75% had NSH. 64% (n = 96) received 2LT and 39% (n = 59) received 3L+T. The top three 1LT were carboplatin+paclitaxel (22%, n = 33), carboplatin+gemcitabine (21%, n = 31), carboplatin+pemetrexed (20%, n = 30). Majority of 2L patients received anti EGFR /anti ALK therapy (n = 50, 52%), most commonly gefitinib (27%, n = 26) and erlotinib (24%, n = 23). 94.0 % of patients (n = 141) had ≥ 1 biopsy performed. Of the 113 NSP, 89% (n = 101) were tested. 97% (n = 101) received an EGFR test, 40% (n = 39) of them were positive. Median OS for Korea from start of 1LT & 2LT was 11.1 and 6.0 months respectively. The average inpatient stay was 15.5 & 13.8 days/admission & the total inpatient admissions were 723 & 618 for Australia & Korea respectively. Conclusions: Platinum combination is commonly used 1LT, pemetrexed in Australia & anti-EGFR agents in Korea are commonly used 2LT in NSP. Among NSP > 70% received BMX.