Pembrolizumab in performance status 2 patients with non-small cell lung cancer (NSCLC): Results of the PePS2 trial

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

doi:10.1093/annonc/mdy292.007

Cited by 24 publications

(24 citation statements)

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“…Historically, patients with ECOG PS > 1 treated with chemotherapy had poor outcomes, with median OS of 1.8e3.6 months [28e30], one-year survival rates of <20% [31], tumour response rates of 16e22% [32], and a high incidence of grade 3e5 TRAEs (44%) [33]. The results presented herein and the findings from previous studies of nivolumab and other antiePD-1 agents [7,24,34,35] suggest that patients with ECOG PS 2 may derive benefit from immunotherapy, with median survival of 4.0e6.8 months [7,24], one-year survival rates of 27% (current study), objective response rates of 11e30% [34e36], and lower incidences of grade 3e4 TRAEs (7% in the current study and 8e12% in previous studies) [24,35]. However, there are concerns over immunotherapy due to the lack of clinical data supporting a favourable benefiterisk profile in this heterogenous population with multiple factors that may contribute to poor performance [37]; randomised studies are warranted to assess clinical benefit in these patients.…”

Section: Discussionmentioning

confidence: 66%

CheckMate 171: A phase 2 trial of nivolumab in patients with previously treated advanced squamous non-small cell lung cancer, including ECOG PS 2 and elderly populations

Felip

Ardizzoni

Ciuleanu

et al. 2020

European Journal of Cancer

135

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Background: CheckMate 171 (NCT02409368) is an open-label, multicentre, phase 2 trial of nivolumab in previously treated advanced squamous non-small cell lung cancer (NSCLC), conducted as part of a post-approval commitment to the European Medicines Agency (EMA). We report outcomes from this trial. Methods: Patients with Eastern Cooperative Oncology Group performance status (ECOG PS) 0e2 and disease progression during/after !1 systemic treatment (!1 being platinum-based chemotherapy) for advanced or metastatic disease were treated with nivolumab 3 mg/kg every 2 weeks until progression or unacceptable toxicity. The primary end-point was incidence of grade 3e4 treatment-related select adverse events (AEs). Other end-points included overall survival (OS) and safety. Results: Of 811 patients treated, 103 had ECOG PS 2; 278 were aged !70 years and 125 were !75 years of age. Minimum follow-up was~18 months. Safety was similar across populations; the most frequent grade 3e4 treatment-related select AEs in all treated patients were diarrhoea (1%), increased alanine aminotransferase (ALT, 1%), pneumonitis (0.7%), colitis (0.6%) and increased aspartate aminotransferase (AST, 0.5%). Median OS was similar in all treated patients and those aged !70 and !75: 10.0 months, 10.0 months and 11.2 months, respectively. Median OS was 5.2 months in patients with ECOG PS 2. Conclusion: These results suggest that nivolumab is well tolerated and active in patients with advanced, relapsed squamous NSCLC, including the elderly, with OS outcomes consistent with phase 3 data. In patients with ECOG PS 2, nivolumab had similar tolerability, but outcomes were worse, as expected in this difficult-to-treat, poor prognosis population. Clinical trial registration: NCT02409368.

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Section: Discussionmentioning

confidence: 66%

CheckMate 171: A phase 2 trial of nivolumab in patients with previously treated advanced squamous non-small cell lung cancer, including ECOG PS 2 and elderly populations

Felip

Ardizzoni

Ciuleanu

et al. 2020

European Journal of Cancer

135

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“…Hence, ECOG PS 2 patients have been usually excluded from ICIs trials and they are also underrepresented in studies specifically designed for special populations not generally included in clinical trials [23]. More data are awaited from ongoing prospective studies assessing the efficacy of immunotherapy (NCT02733159, NCT02879617) in ECOG PS 2 NSCLC patients [24,25]. Whether ECOG PS is a prognostic and/or predictive biomarker in patients treated with ICIs remains an open question so far.…”

Section: Discussionmentioning

confidence: 99%

EPSILoN: A Prognostic Score for Immunotherapy in Advanced Non-Small-Cell Lung Cancer: A Validation Cohort

Prelaj

Ferrara

Rebuzzi

et al. 2019

Cancers

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Background: Beyond programmed death ligand 1 (PD-L1), no other biomarkers for immunotherapy are used in daily practice. We previously created EPSILoN (Eastern Cooperative Oncology Group performance status (ECOG PS), smoking, liver metastases, lactate dehydrogenase (LDH), neutrophil-to-lymphocyte ratio (NLR)) score, a clinical/biochemical prognostic score, in 154 patients treated with second/further-line immunotherapy. This study’s aim was to validate EPSILoN score in a different population group. Methods: 193 patients were included at National Cancer Institute of Milan (second-line immunotherapy, 61%; further-line immunotherapy, 39%). Clinical/laboratory parameters such as neutrophil-to-lymphocyte ratio and lactate dehydrogenase levels were collected. Kaplan–Meier and Cox hazard methods were used for survival analysis. Results: Overall median progression-free survival and median overall survival were 2.3 and 7.6 months, respectively. Multivariate analyses for Progression-Free Survival (PFS) identified heavy smokers (hazard ratio (HR) 0.71, p = 0.036) and baseline LDH < 400 mg/dL (HR 0.66, p = 0.026) as independent positive factors and liver metastases (HR 1.48, p = 0.04) and NLR ≥ 4 (HR 1.49, p = 0.029) as negative prognostic factors. These five factors were included in the EPSILoN score which was able to stratify patients in three different prognostic groups, high, intermediate and low, with PFS of 6.0, 3.8 and 1.9 months, respectively (HR 1.94, p < 0.001); high, intermediate and low prognostic groups had overall survival (OS) of 24.5, 8.9 and 3.4 months, respectively (HR 2.40, p < 0.001). Conclusions: EPSILoN, combining five baseline clinical/blood parameters (ECOG PS, smoking, liver metastases, LDH, NLR), may help to identify advanced non-small-cell lung cancer (aNSCLC) patients who most likely benefit from immune checkpoint inhibitors (ICIs).

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“…Unfortunately, however, the evidence for making treatment decisions about using ICIs in this group of patients is scant. Among the only five trials of ICIs in NSCLC that allowed the inclusion of PS 2 patients, only one (PePS2 trial) 40 is specific to addressing the activity of ICIs in this population (Table 1).…”

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confidence: 99%

“…Recently, interesting preliminary data were presented from the PePS2 trial, investigating the role of pembrolizumab in ECOG PS 2 patients, including treatment-naïve and pretreated patients. 40 Globally, 60 patients were enrolled in the trial, of whom nine were treatment naïve and 15 had a strong programmed death-ligand 1 (PD-L1) expression ($ 50%). The results in the overall patient population showed an overall response rate of 28.3% and a median PFS and OS of 5.4 and 11.7 months, respectively.…”

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confidence: 99%

Immunotherapy in Non–Small-Cell Lung Cancer Patients With Performance Status 2: Clinical Decision Making With Scant Evidence

Passaro

Spitaleri

Gyawali

et al. 2019

JCO

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Pembrolizumab in performance status 2 patients with non-small cell lung cancer (NSCLC): Results of the PePS2 trial

Cited by 24 publications

References 0 publications

CheckMate 171: A phase 2 trial of nivolumab in patients with previously treated advanced squamous non-small cell lung cancer, including ECOG PS 2 and elderly populations

CheckMate 171: A phase 2 trial of nivolumab in patients with previously treated advanced squamous non-small cell lung cancer, including ECOG PS 2 and elderly populations

EPSILoN: A Prognostic Score for Immunotherapy in Advanced Non-Small-Cell Lung Cancer: A Validation Cohort

Immunotherapy in Non–Small-Cell Lung Cancer Patients With Performance Status 2: Clinical Decision Making With Scant Evidence

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