- •Evidence on first-line pembrolizumab in Eastern Cooperative Oncology Group performance status (PS) 2 non–small cell lung cancer (NSCLC) (PD-L1 ≥ 50%) are poor.
- •This retrospective study documented dismal outcomes in this population of interest.
- •Patients with disease burden-determined poor PS had poor prognosis.
- •Comorbidity-induced PS 2 may still benefit form pembrolizumab.
- •The differential determinants of PS 2 in NSCLC are relevant for clinical decisions.
Pembrolizumab is the first-line standard of care for advanced non–small cell lung cancer (NSCLC) with a PD-L1 tumour proportion score (TPS) ≥ 50%. Eastern Cooperative Oncology Group performance status (PS) 2 patients may receive pembrolizumab, despite the absence of sustaining evidence.
Patients and methods
GOIRC-2018-01 is a multicentre, retrospective, observational study. PS 2 NSCLC patients with a PD-L1 TPS ≥50% receiving first-line pembrolizumab from June 2017 to December 2018 at 21 Italian institutions were included. Clinical-pathological characteristics were correlated with disease response and survival outcomes; adverse events were recorded. The primary objective was 6-months progression-free rate (6-months PFR).
One hundred fifty-three patients (median age 70 years) were enrolled. At a median follow-up of 18.2 months, median progression-free survival (PFS) and overall survival (OS) were 2.4 (95% confidence interval, 95% CI, 1.6–2.5) and 3.0 months (95% CI 2.4–3.5), respectively. 6-months PFR was 27% (95% CI 21–35%). Patients with a PS 2 determined by comorbidities (n = 41) had significantly better outcomes compared with disease burden-induced PS 2 (n = 112). Indeed, 6-months PFR was 49% versus 19%, median PFS 5.6 versus 1.8 months and OS 11.8 versus 2.8 months, respectively. Additional potential prognostic factors (radiotherapy, antibiotics, steroids received before pembrolizumab) correlated with clinical outcomes. The determinant of PS 2 resulted the only factor independently impacting on both PFS and OS. No toxicity issues emerged.
Outcomes of PS 2 NSCLC patients with PD-L1 TPS ≥50% receiving first-line pembrolizumab were globally dismal but strongly dependent on the reason conditioning the poor PS itself.
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- Five-year long-term overall survival for patients with advanced NSCLC treated with pembrolizumab: results from KEYNOTE-001.J Clin Oncol. 2019; 37 (LBA9015–LBA9015)https://doi.org/10.1200/JCO.2019.37.18_suppl.LBA9015
- Four-year survival with nivolumab in patients with previously treated advanced non-small-cell lung cancer: a pooled analysis.Lancet Oncol. 2019; 20: 1395-1408https://doi.org/10.1016/s1470-2045(19)30407-3
- Pembrolizumab versus chemotherapy for PD-L1–positive non–small-cell lung cancer.N Engl J Med. 2016; 375: 1823-1833https://doi.org/10.1056/NEJMoa1606774
- OA14.01 KEYNOTE-024 3-year survival update: pembrolizumab versus platinum-based chemotherapy for advanced non–small-cell lung cancer.J Thorac Oncol. 2019; 14: S243
- Treatment of elderly patients or patients who are performance status 2 (PS2) with advanced Non-Small Cell Lung Cancer without epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) translocations – still a daily challenge.Eur J Cancer. 2017; 83: 266-278https://doi.org/10.1016/j.ejca.2017.07.002
- 1303PDNivolumab in previously treated patients with metastatic squamous NSCLC: results of a European single-arm, phase 2 trial (CheckMate 171) including patients aged ≥70 years and with poor performance status.Ann Oncol. 2017; 28https://doi.org/10.1093/annonc/mdx380.006
- P2.07-029 CheckMate 169: safety/efficacy of nivolumab in Canadian pretreated advanced NSCLC (including elderly and PS 2) patients.J Thorac Oncol. 2017; 12: S2426-S2427https://doi.org/10.1016/j.jtho.2017.11.088
- 1302PDIFCT-1502 CLINIVO: real-life experience with nivolumab in 600 patients (pts) with advanced non-small cell lung cancer (NSCLC): efficacy and safety of nivolumab and post-nivolumab treatment in the French Expanded Access Program (EAP).Ann Oncol. 2017; 28https://doi.org/10.1093/annonc/mdx380.005
- Safety, efficacy, and patient-reported health-related quality of life and symptom burden with nivolumab in patients with advanced non–small cell lung cancer, including patients aged 70 Years or older with poor performance status (CheckMate 153).J Thorac Oncol. 2019; https://doi.org/10.1016/j.jtho.2019.05.010
- Primary results from TAIL, a global single-arm safety study of atezolizumab (atezo) monotherapy in a diverse population of patients with previously treated advanced non-small cell lung cancer (NSCLC).Ann Oncol. 2019; 30: LBA84
- PePS2: pembrolizumab in Performance Status 2 non-small-cell lung cancer (NSCLC): results of the PePS2 trial.Ann Oncol. 2018; 29 (1384PD)
- Metastatic non-small cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.Ann Oncol. 2018; 29: iv192-iv237
- Treatment of metastatic non-small cell lung cancer: 2018 guidelines of the Italian Association of Medical Oncology (AIOM).Tumori. 2019; 105: 3-14https://doi.org/10.1177/0300891619857418
- Immune checkpoint blockade for non–small cell lung cancer: what is the role in the special populations?.Eur J Cancer. 2020; 125: 1-11
- PD-L1 immunohistochemistry assays for lung cancer: results from phase 1 of the blueprint PD-L1 IHC assay comparison project.J Thorac Oncol. 2017; 12: 208-222https://doi.org/10.1016/j.jtho.2016.11.2228
- PD-L1 immunohistochemistry comparability study in real-life clinical samples: results of blueprint phase 2 project.J Thorac Oncol. 2018; https://doi.org/10.1016/j.jtho.2018.05.013
- A prospective, multi-institutional, pathologist-based assessment of 4 immunohistochemistry assays for PD-L1 expression in non–small cell lung cancer.JAMA Oncol. 2017; 3: 1051-1058https://doi.org/10.1001/jamaoncol.2017.0013
- Randomized phase III trial of single-agent pemetrexed versus carboplatin and pemetrexed in patients with advanced non-small-cell lung cancer and Eastern Cooperative Oncology Group performance status of 2.J Clin Oncol. 2013; 31: 2849-2853https://doi.org/10.1200/JCO.2012.48.1911
- A note on quantifying follow-up in studies of failure time.Contr Clin Trial. 1996; 17: 343-346https://doi.org/10.1016/0197-2456(96)00075-X
- Immune checkpoint inhibitor outcomes for patients with non–small-cell lung cancer receiving baseline corticosteroids for palliative versus nonpalliative indications.J Clin Oncol. 2019; 37: 1927-1934https://doi.org/10.1200/jco.19.00189
- Outcomes to first-line pembrolizumab in patients with non-small-cell lung cancer and very high PD-L1 expression.Ann Oncol. 2019; https://doi.org/10.1093/annonc/mdz288
- Impact of baseline steroids on efficacy of programmed cell death-1 and programmed death-ligand 1 blockade in patients with non–small-cell lung cancer.J Clin Oncol. 2018; 36: 2872-2878https://doi.org/10.1200/JCO.2018.79.0006
- Negative association of antibiotics on clinical activity of immune checkpoint inhibitors in patients with advanced renal cell and non-small-cell lung cancer.Ann Oncol. 2018; 29: 1437-1444https://doi.org/10.1093/annonc/mdy103
- Pneumonitis in irradiated lungs after nivolumab: a brief communication and review of the literature.J Immunother. 2018; 41: 96-99https://doi.org/10.1097/CJI.0000000000000198
- Immunotherapy in non–small-cell lung cancer patients with performance status 2: clinical decision making with scant evidence.J Clin Oncol. 2019; 37: 1863-1867https://doi.org/10.1200/jco.18.02118
- First-line pembrolizumab monotherapy for metastatic PD-L1-positive NSCLC: real-world analysis of time on treatment.Immunotherapy. 2019; 11: 889-901https://doi.org/10.2217/imt-2019-0061
- Association between metastatic sites and first-line pembrolizumab treatment outcome for advanced non–small cell lung cancer with high PD-L1 expression: a retrospective multicenter cohort study.Invest New Drugs. 2020; 8: 211-218
- Clinical outcomes in non-small cell lung cancer patients with an ultra-high expression of programmed death ligand-1 treated using pembrolizumab as a first-line therapy: a retrospective multicenter cohort study in Japan.PloS One. 2019; 14e0220570https://doi.org/10.1371/journal.pone.0220570
- First line pembrolizumab for NSCLC with PD-L1 TPS > 50% in a first French real life cohort.Ann Oncol. 2019; 30: 1502P
- Carlos Silva 4 6 Gonzalo Recondo1. First line treatment with pembrolizumab in patients with non-small cell lung cancer and PD-L1 tumor proportion score (TPS) ≥ 50%: real-world study in Argentina.J Thorac Oncol. 2019; 14: S589-S590
- Pembrolizumab with high PD-L1: who are non-responders?.J Thorac Oncol. 2019; 14: S974
- Efficacy and safety of first-line pembrolizumabmonotherapyin elderly patients (aged ≥ 75 years) with non-small cell lung cancer.J Thorac Oncol. 2019; 14: S453
- Efficacy and safety of pembrolizumab as first-line therapy in advanced non-small cell lung cancer with at least 50% PD-L1 positivity: a multicenter retrospective cohort study (HOPE-001).Invest N Drug. 2019; https://doi.org/10.1007/s10637-019-00843-y
- 1499PPembrolizumab as first-line treatment in NSCLC with PD-L1 ≥50%: real life results from an all-comer population.Ann Oncol. 2019; 30https://doi.org/10.1093/annonc/mdz260.021
- 1262PPredictive model for survival in advanced non-small cell lung cancer (NSCLC) treated with frontline pembrolizumab.Ann Oncol. 2019; 30https://doi.org/10.1093/annonc/mdz253.087
- Previous radiotherapy and the clinical activity and toxicity of pembrolizumab in the treatment of non-small-cell lung cancer: a secondary analysis of the KEYNOTE-001 phase 1 trial.Lancet Oncol. 2017; 18: 895-903https://doi.org/10.1016/S1470-2045(17)30380-7
- Prior radiotherapy does not predict nivolumab response in non-small-cell lung cancer: a retrospective cohort study.Ann Oncol. 2017; 28: 1402https://doi.org/10.1093/annonc/mdx114
- Choosing wisely first line immunotherapy in non-small cell lung cancer (NSCLC): what to add and what to leave out.Cancer Treat Rev. 2019; 75: 39-51https://doi.org/10.1016/j.ctrv.2019.03.004
- Pembrolizumab exposure–response assessments challenged by association of cancer cachexia and catabolic clearance.Clin Cancer Res. 2018; 24: 5841-5849https://doi.org/10.1158/1078-0432.CCR-18-0415
- Nivolumab plus ipilimumab in advanced non–small-cell lung cancer.N Engl J Med. 2019; https://doi.org/10.1056/nejmoa1910231
- OA04.02 CheckMate 817: first-line nivolumab + ipilimumab in patients with ECOG PS 2 and other special populations with advanced NSCLC.J Thorac Oncol. 2019; 14: S214-S215https://doi.org/10.1016/j.jtho.2019.08.424
- Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial.Lancet. 2019; 393: 1819-1830https://doi.org/10.1016/S0140-6736(18)32409-7
- Pembrolizumab plus chemotherapy in metastatic non–small-cell lung cancer.N Engl J Med. 2018; 378: 2078-2092https://doi.org/10.1056/nejmoa1801005
- Pembrolizumab plus chemotherapy for squamous non-small-cell lung cancer.N Engl J Med. 2018; 379: 2040-2051
- Circulating immune biomarkers as predictors of the response to pembrolizumab and weekly low dose carboplatin and paclitaxel in NSCLC and poor PS: an interim analysis.Oncol Lett. 2019; 17: 1349-1356https://doi.org/10.3892/ol.2018.9724
Published online: March 25, 2020
Accepted: February 20, 2020
Received in revised form: February 20, 2020
Received: January 12, 2020
© 2020 Elsevier Ltd. All rights reserved.