Pembrolizumab in patients with non-small-cell lung cancer of performance status 2 (PePS2): a single arm, phase 2 trial

Middleton, Gary; Brock, Kristian; Savage, Joshua; Mant, Rhys; Summers, Yvonne; Connibear, John; Shah, Riyaz; Ottensmeier, Christian; Shaw, Paul; Lee, Siow Ming; Popat, Sanjay; Barrie, Colin; Barone, Gloria; Billingham, Lucinda

doi:10.1016/s2213-2600(20)30033-3

Cited by 136 publications

(97 citation statements)

References 20 publications

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“…Limited data are available on the safety and efficacy of immunotherapy in NSCLC patients with poor PS (16). Only 4 recently published clinical trials (CheckMate 171, CheckMate 153, CheckMate 817, and PePS2) include a small number of PS 2 NSCLC patients, showing results of ORR, median PFS and OS ranging from 20% to 27%, 3.6 to 4.4 months, and 4.0 to 9.8 months, respectively (3)(4)(5). However, with the exception of PePS2, the populations of the other 3 trials were heterogeneous, consisting of a mix of elderly patients and PS <2 patients with comorbidities.…”

Section: Discussionmentioning

confidence: 99%

“…The success of anti-programmed cell death 1 (PD-1) therapy has revolutionized the treatment landscape for NSCLC patients, however the survival benefit in poor PS patients remains controversial, mainly due to the inclusion criteria of most clinical trials of patients with PS 0-1. So far, only 4 prospective trials, including a small number of PS 2 patients receiving immunotherapy, have been published, with the overall response rate (ORR), median progressionfree survival (PFS), and overall survival (OS) ranging from 20% to 27%, 3.6 to 4.4 months, and 4 to 9.8 months, respectively (3)(4)(5)(6). Therefore, it is an urgent demand for NSCLC patients with PS 2-4 to investigate the safety and efficacy of immunotherapy.…”

Section: Introductionmentioning

confidence: 99%

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Prognostic value of baseline and change in neutrophil-to-lymphocyte ratio for survival in advanced non-small cell lung cancer patients with poor performance status receiving PD-1 inhibitors

Chen

Zhang³

et al. 2021

Transl Lung Cancer Res

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Background: Advanced non-small cell lung cancer (NSCLC) patients with poor performance status (PS) are likely to receive programmed cell death 1 (PD-1) inhibitors, despite limited evidence. The aim of the present study was to report the clinical outcomes and potential prognostic biomarkers in advanced NSCLC patients with poor PS receiving PD-1 inhibitors.Methods: We conducted a retrospective study enrolling 101 advanced NSCLC patients from our hospital. Data of patients with poor PS 2-4 receiving PD-1 inhibitors were retrieved from medical records. Patients were stratified based on dichotomized baseline neutrophil-to-lymphocyte ratio (NLR), change in NLR (ΔNLR; 6 weeks post-treatment NLR minus baseline NLR), and their combination. The receiver-operating characteristic curve was used to assess the best cutoff for NLR. Multivariate Cox analysis was used to evaluate the prognostic value of NLR and ΔNLR for patients' survival.Results: The optimal cutoff for NLR was 4.5. The median follow-up was 25.7 months, baseline NLR ≥4.5, and ΔNLR ≥0, which were independently and significantly associated with shorter overall survival (both P=0.002) and progression-free survival (P=0.004 for NLR and P<0.001 for ΔNLR). Furthermore, simultaneous elevation of the 2 factors was associated with worsened prognosis; patients with both NLR ≥4.5 and ΔNLR ≥0 had significantly increased risk of death [hazards ratio (HR): 10.79, 95% confidence interval (

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Prognostic value of baseline and change in neutrophil-to-lymphocyte ratio for survival in advanced non-small cell lung cancer patients with poor performance status receiving PD-1 inhibitors

Chen

Zhang³

et al. 2021

Transl Lung Cancer Res

View full text Add to dashboard Cite

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“… 1–4 13 14 Although the PePS2 study specifically evaluated the safety and tolerability of pembrolizumab in 60 patients with an ECOG PS of 2, only a small subset of 10 patients received pembrolizumab in the first-line setting with a PD-L1 TPS of ≥50%. 15 Here, were report outcomes among 234 patients treated with first-line commercial pembrolizumab. Because non-clinical trial populations generally do not perform as well as clinical trial participants, 16 we compared clinical outcomes in 39 patients with an ECOG PS of 2 to 195 patients with an ECOG PS of 0–1; all patients were treated outside the setting of a clinical trial to control for the potential impact of studying outcomes in a non-clinical trial group.…”

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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“…Two trials have been recently published: PePs2 and the GOIRC-2018. The primary endpoints of the PePS2, which was a prospective phase II single-arm trial (38), were toxicity and durable clinical benefit, defined as disease stability or better at 6 months. A total of 60 patients with PS ECOG 2 were recruited among the 122 assessed.…”

Section: How Does Sars-cov-2 Impact Treatment Duration?mentioning

confidence: 99%

Rethinking the Optimal Duration of Immune Checkpoint Inhibitors in Non-small Cell Lung Cancer Throughout the COVID-19 Pandemic

2020

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Immune checkpoint inhibitors (ICPIs) have revolutionized the management and prognosis of fit patients with advanced non-small cell lung cancer (NSCLC). Recently, the publication of 5-year survival rates has cemented the role of ICPIs in NSCLC. An ongoing challenge is to determine the optimal treatment duration to find the balance between efficacy, toxicity and cost. From the onset of ICPI trials, different durations were used, ranging from treatment until progression or toxicity, to fixed durations of 2 years. Subsequently, exploratory analyses from a 1-year fixed duration trial failed to change practice. There are, to date, no adequately powered prospective trials addressing this important question. With today's severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) pandemic, more than ever, the question resurfaces with added factors tilting the already shaky therapeutic balance. Here, we will discuss current data regarding ICPI treatment duration and incorporate this into the context of the ongoing pandemic. We conclude with a discussion of pragmatic approaches, should physicians be unable to continue standard therapy.

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Pembrolizumab in patients with non-small-cell lung cancer of performance status 2 (PePS2): a single arm, phase 2 trial

Abstract: in patients with non-smallcell lung cancer of performance status 2 (PePS2): a single arm, phase 2 trial. Lancet Respiratory Medicine 8 (9) , pp.

Cited by 136 publications

References 20 publications

Prognostic value of baseline and change in neutrophil-to-lymphocyte ratio for survival in advanced non-small cell lung cancer patients with poor performance status receiving PD-1 inhibitors

Prognostic value of baseline and change in neutrophil-to-lymphocyte ratio for survival in advanced non-small cell lung cancer patients with poor performance status receiving PD-1 inhibitors

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

Rethinking the Optimal Duration of Immune Checkpoint Inhibitors in Non-small Cell Lung Cancer Throughout the COVID-19 Pandemic

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