OA04.02 CheckMate 817: First-Line Nivolumab + Ipilimumab in Patients with ECOG PS 2 and Other Special Populations with Advanced NSCLC

Audigier-Valette, Clarisse; Felip, Enriqueta; Ciuleanu, Tudor; Jao, Kevin; Rijavec, E.; Urbán, László; Aucoin, Jean-Sebastien; Zannori, Cristina; Vermaelen, Karim; Frontera, Osvaldo Arén; Ready, Neal; Curioni-Fontecedro, Alessandra; Linardou, Helena; Poddubskaya, Elena; Fischer, J. R.; Iordan, Iuliana; Groen, Harry J.M.; Pillai, Rathi N.; Li, S.; Fiore, Joseph; Han, Chang; Acevedo, A.; Paz-Ares, L.

doi:10.1016/j.jtho.2019.08.424

Cited by 48 publications

(36 citation statements)

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“…As in the recent PePS2 trial, Checkmate 171 and Checkmate 817, we see that some patients with PS2 do appear to benefit from checkpoint inhibitors [9,26]. The PePS2 trial prospectively collected safety and efficacy outcomes on 60 NSCLC patients with PS2 treated with single agent pembrolizumab [10].…”

Section: Discussionmentioning

confidence: 87%

“…The Checkmate 817 trial evaluated the role of combined nivolumab and ipilimumab, an anti-CTLA4, in special populations of NSCLC patients, including those with PS2 [26]. While the treatment-related adverse events were not increased compared to patients with a PS of 0-1, the efficacy was lower among patients with PS2, with a 19% overall response rate (ORR) and 3.6 months median progression-free survival (PFS), compared to a 36% and 5.8 months, respectively, among fitter patients.…”

Section: Discussionmentioning

confidence: 99%

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Impact of performance status on non-small-cell lung cancer patients with a PD-L1 tumour proportion score ≥50% treated with front-line pembrolizumab

et al. 2020

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Objectives: We retrospectively analysed patients with advanced non-small-cell lung cancer (NSCLC) harbouring high PD-L1 expression (>50%) and treated with front-line pembrolizumab, comparing outcomes of patients with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) 2 to those with PS 0-1. Methods: Data were collected by 16 participating centres. All patients with NSCLC and high PD-L1, treated with first-line pembrolizumab were included. We collected medical data from patient files, pathology and laboratory reports. Patient characteristics, comorbidities, PS, and tumour characteristics were reported. Overall survival (OS), progression-free survival (PFS) and response rate (RR) were calculated. Results: 302 patients were included, 246 with PS 0-1, 56 with PS 2. RR was 72% among patients with PS 0-1 compared to 45% with PS2 (odds ratio (OR) 0.31 (95% CI: 0.17-0.57), p < .001). Median PFS was 2.6 months (95% CI: 1.9-5.1) among patients with PS2 and 11.3 months (95% CI: 8.5-14.4) among those with PS 0-1. Median OS was 7.8 months (95% CI: 2.5-10.7) in the PS2 group, not reached in the PS 0-1 group. PS 2 remained predictive of poor outcomes in multivariate analysis. Conclusion: PS 2 is a strong independent predictor of poor response and survival in NSCLC patients with high PD-L1, treated with front-line pembrolizumab. Prospective randomised trials comparing immunotherapy to chemotherapy in this population would be welcome.

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Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Impact of performance status on non-small-cell lung cancer patients with a PD-L1 tumour proportion score ≥50% treated with front-line pembrolizumab

et al. 2020

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“…Prospective studies will hopefully help define the best initial treatment approach for this vulnerable population. Preliminary data from CheckMate 817 of first-line ipilimumab plus nivolumab in patients with either an ECOG PS 2 or with a comorbidity (such as asymptomatic untreated brain metastases, hepatic or renal impairment, HIV) 18 showed a promising mPFS of 9.6 months in patients with PD-L1 TPS ≥50% (n=33). Another prospective study (eNERGY, NCT03351361) will compare first-line ipilimumab plus nivolumab with carboplatin-based doublet chemotherapy in patients with an ECOG PS 2.…”

Section: Discussionmentioning

confidence: 99%

Outcomes to first-line pembrolizumab in patients with PD-L1-high (≥50%) non–small cell lung cancer and a poor performance status

Alessi

Ricciuti

Jimenez-Aguilar

et al. 2020

J Immunother Cancer

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BackgroundPatients with non–small cell lung cancer (NSCLC) and a poor Eastern Cooperative Oncology Group Performance Status (ECOG PS) have been excluded from phase III immunotherapy clinical trials. We sought to evaluate clinical outcomes to first-line pembrolizumab in patients with advanced NSCLC, a PD-L1 Tumor Proportion Score (TPS) of ≥50%, and an ECOG PS of 2.MethodsWe performed a multicenter retrospective analysis of patients with metastatic NSCLC and a PD-L1 TPS of ≥50% (negative for genomic alterations in EGFR and ALK) who received treatment with first-line pembrolizumab. Clinical outcomes were compared in patients based on ECOG PS.ResultsAmong the 234 patients, 83.3% (n=195) had an ECOG PS of 0 or 1, and 16.7% (n=39) had an ECOG PS of 2. The baseline clinicopathological characteristics were balanced between the ECOG PS 0–1 vs 2 groups in terms of age, sex, tobacco use, histology, KRAS mutation status, presence of other potentially targetable driver mutations (BRAF, MET, HER2, RET), presence of brain metastases, and PD-L1 TPS distribution. Compared with patients with an ECOG PS of 0 or 1, patients with an ECOG PS of 2 had a significantly lower objective response rate (43.1% vs 25.6%; p=0.04), a numerically shorter median progression-free survival (6.6 months vs 4.0 months; HR 0.70 (95% CI 0.47 to 1.06); p=0.09), and a significantly shorter median overall survival (20.3 months vs 7.4 months; HR 0.42 (95% CI 0.26 to 0.68); p<0.001). On disease progression, patients with an ECOG PS of 2 were significantly less likely to receive second-line systemic therapy compared with patients with an ECOG PS of 0–1 (65% vs 22.2%, p=0.001).ConclusionsA subset of patients with NSCLC and an ECOG PS of 2 can respond to first-line pembrolizumab. However, clinical outcomes in this population are often poor and use of second-line systemic therapy is infrequent.

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“…Thus, clinical trial data to support the use of ICIs in patients with NSCLC who have impaired PS (≥2) are limited, despite an estimated prevalence of PS ≥2 among newly diagnosed adults with lung cancer of approximately 34% . One single‐arm, nonrandomized, prospective study (Checkmate 817 [An Investigational Immuno‐therapy Study for Safety of Nivolumab in Combination With Ipilimumab to Treat Advanced Cancers; clinicaltrials.gov identifier NCT02869789]) of patients with advanced lung cancer who were treated with combination nivolumab and ipilimumab showed comparable rates of toxicity among patients who had an ECOG PS 2 or significant comorbidities relative to those who had PS 0 or 1 . An additional prospective, nonrandomized study of 62 patients with advanced NSCLC and PS 2 who received with pembrolizumab reported grade 3 or 4 immune‐related adverse events in 8% and an objective response rate of 30% .…”

Section: Introductionmentioning

confidence: 99%

Performance status and end‐of‐life care among adults with non–small cell lung cancer receiving immune checkpoint inhibitors

Petrillo

El‐Jawahri

Nipp

et al. 2020

Cancer

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BACKGROUND: Adults with impaired performance status (PS) often receive immune checkpoint inhibitors (ICIs) for advanced non-small cell lung cancer (NSCLC) despite limited efficacy data and unknown effects on end-of-life care. METHODS: This was a retrospective, single-site study of 237 patients with advanced NSCLC who initiated ICI treatment from 2015 to 2017. Cox regression was used to compare the overall survival (OS) of patients who had impaired PS (≥2) at the start of ICI treatment with those who had PS 0 or 1 using Cox regression. Logistic regression was conducted to analyze the association between ICI use in the last 30 days of life and the use of end-oflife health care. RESULTS: The patient mean age at ICI initiation was 67 years (range, 37-91 years), and 35.4% of patients had PS ≥2. Most patients (80.8%) received ICI as second-line or later therapy. The median OS was 4.5 months in patients with PS ≥2 and 14.3 months in those with PS 0 or 1 (hazard ratio, 2.5; P < .0001). Among the patients who died (n = 184), 28.8% who had PS ≥2 received ICIs in their last 30 days of life compared with 10.8% of those who had PS 0 or 1 (P = .002). Receipt of ICI in the last 30 days of life was associated with decreased hospice referral (odds ratio, 0.29; P = .008) and increased in-hospital deaths (odds ratio, 6.8; P = .001), independent of PS. CONCLUSIONS: Adults with advanced NSCLC and impaired PS experience significantly shorter survival after ICI treatment and receive ICIs near death more often than those with better PS. Receipt of an ICI near death was associated with lower hospice use and an increased risk of death in the hospital. These results underscore the need for high-quality communication about potential tradeoffs of ICIs, particularly among adults receiving ICIs as second-line or later therapy. Cancer 2020;126:2288-2295.

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OA04.02 CheckMate 817: First-Line Nivolumab + Ipilimumab in Patients with ECOG PS 2 and Other Special Populations with Advanced NSCLC

Cited by 48 publications

References 0 publications

Impact of performance status on non-small-cell lung cancer patients with a PD-L1 tumour proportion score ≥50% treated with front-line pembrolizumab

Impact of performance status on non-small-cell lung cancer patients with a PD-L1 tumour proportion score ≥50% treated with front-line pembrolizumab

Outcomes to first-line pembrolizumab in patients with PD-L1-high (≥50%) non–small cell lung cancer and a poor performance status

Performance status and end‐of‐life care among adults with non–small cell lung cancer receiving immune checkpoint inhibitors

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