Long-Lasting Therapeutic Response following Treatment with Pembrolizumab in Patients with Non-Small Cell Lung Cancer: A Real-World Experience

Immune checkpoint inhibitors (ICIs), pembrolizumab in particular, have been shown to be vastly more efficacious than traditional cytotoxic or platinum-based chemotherapies in the treatment of non-small cell lung cancer (NSCLC). While there are plenty of data showing their efficacy and safety profiles, very little exists about the long-term effects of pembrolizumab. We compiled all patients with NSCLC who were treated with pembrolizumab at our institution and had progression-free survival (PFS) of at least 2 years during or after the treatment period. Within this group, we examined the long-term rates of PFS and overall survival (OS), side effect profiles, treatment, and overall disease course up to 60 months after starting treatment. This study included 36 patients with median (range) follow up times from treatment initiation in months as follows: 36 (28–65) overall; 39.5 (28–65) for adenocarcinoma; and 36 (30–58) for squamous cell carcinoma. The median (range) of OS and PFS (months) was comparable for adenocarcinoma, 36 (23–55); and squamous cell carcinoma, 35.5 (28–65). Overall, pembrolizumab shows remarkable long-term safety and efficacy in NSCLC patients. In patients who show an initially strong response and can make it to 24 months of PFS, disease progression after this period seems increasingly unlikely.

[1]  O. A. Abu Saleh,et al.  A Retrospective, Single-Institution Experience of Bullous Pemphigoid as an Adverse Effect of Immune Checkpoint Inhibitors , 2022, Cancers.

[2]  N. Peled,et al.  Crizotinib in MET Exon 14-Mutated or MET-Amplified in Advanced Disease Non-Small Cell Lung Cancer: A Retrospective, Single Institution Experience , 2022, Oncology.

[3]  L. Evelson,et al.  Applying methods of twin comparing quantitative and binary samples in biomedical information systems for decision making , 2022, Vestnik of Astrakhan State Technical University. Series: Management, computer science and informatics.

[4]  A. Agbarya,et al.  Neoadjuvant and Adjuvant Immunotherapy in Early-Stage Non-Small-Cell Lung Cancer, Past, Present, and Future , 2021, Journal of clinical medicine.

[5]  A. Yakobson,et al.  Cardiac Toxicity Associated with Immune Checkpoint Inhibitors: A Systematic Review , 2021, Cancers.

[6]  A. Agbarya,et al.  Adjuvant Treatment with Tyrosine Kinase Inhibitors in Epidermal Growth Factor Receptor Mutated Non-Small-Cell Lung Carcinoma Patients, Past, Present and Future , 2021, Cancers.

[7]  L. Sequist,et al.  Lung cancer , 2021, The Lancet.

[8]  A. Tafreshi,et al.  Outcomes With Pembrolizumab Plus Platinum-Based Chemotherapy for Patients With Non-Small-Cell Lung Cancer and Stable Brain Metastases: Pooled Analysis of KEYNOTE-021, 189, and 407. , 2021, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[9]  A. Porgador,et al.  Rapid Response to the Combination of Lenvatinib and Pembrolizumab in Patients with Advanced Carcinomas (Lung Adenocarcinoma and Malignant Pleural Mesothelioma) , 2021, Cancers.

[10]  A. Tafreshi,et al.  A Randomized, Placebo-Controlled Trial of Pembrolizumab Plus Chemotherapy in Patients With Metastatic Squamous Non-Small-Cell Lung Cancer: Protocol-Specified Final Analysis of KEYNOTE-407. , 2020, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[11]  N. Peled,et al.  Associated Myocarditis: A Predictive Factor for Response? , 2020, Case Reports in Oncology.

[12]  J. Weiss,et al.  Advances in the Treatment of Non-Small Cell Lung Cancer: Immunotherapy. , 2020, Clinics in chest medicine.

[13]  S. Novello,et al.  Updated Analysis From KEYNOTE-189: Pembrolizumab or Placebo Plus Pemetrexed and Platinum for Previously Untreated Metastatic Nonsquamous Non-Small-Cell Lung Cancer. , 2020, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[14]  A. Gemma,et al.  Immune checkpoint inhibitor‐associated interstitial lung diseases correlate with better prognosis in patients with advanced non‐small‐cell lung cancer , 2020, Thoracic cancer.

[15]  S. Kimura,et al.  Discontinuation due to immune‐related adverse events is a possible predictive factor for immune checkpoint inhibitors in patients with non‐small cell lung cancer , 2019, Thoracic cancer.

[16]  Jianying Zhou,et al.  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 , 2019, The Lancet.

[17]  Yi-long Wu,et al.  Emerging therapies for non-small cell lung cancer , 2019, Journal of Hematology & Oncology.

[18]  A. Tafreshi,et al.  Updated Analysis of KEYNOTE-024: Pembrolizumab Versus Platinum-Based Chemotherapy for Advanced Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score of 50% or Greater. , 2019, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[19]  C. Presley,et al.  Checkpoint Inhibitors for Non-Small Cell Lung Cancer Among Older Adults , 2017, Current Oncology Reports.

[20]  I. Tabbara,et al.  Immune-based Therapies for Non-small Cell Lung Cancer. , 2017, Anticancer research.

[21]  Y. Shentu,et al.  Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. , 2016, The New England journal of medicine.

[22]  Y. Shentu,et al.  Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial , 2016, The Lancet.

[23]  L. Horn Advances in the treatment of non-small cell lung cancer. , 2014, Journal of the National Comprehensive Cancer Network : JNCCN.

[24]  D. Gerber,et al.  Maintenance chemotherapy for advanced non-small-cell lung cancer: new life for an old idea. , 2013, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[25]  Drew M. Pardoll,et al.  The blockade of immune checkpoints in cancer immunotherapy , 2012, Nature Reviews Cancer.

[26]  Haidong Dong,et al.  Tumor-associated B7-H1 promotes T-cell apoptosis: A potential mechanism of immune evasion , 2002, Nature Medicine.

[27]  D. Brizel,et al.  National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology , 2012 .