Published data from Merck's pembrolizumab adjuvant treatment in patients with stage IB-IIIA non-small cell lung cancer (NSCLC)

Merck & Co (Merck is a corporate name of Merck & Co.
, Kenilworth, NJ, USA), the European Organization for Research and Treatment of Cancer (EORTC) and the European Platform for Thoracic Oncology (ETOP) announced their pivotal Phase III clinical trial KEYNOTE-091 ( Also known as EORTC-1416-LCG/ETOP-8-15-PEARLS) study data
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The study was designed to evaluate the Merck PD-1 inhibitor pembrolizumab versus placebo, with or without adjuvant chemotherapy, for surgery in patients with stage IB (T ≥ 4 cm) to stage IIIA non-small cell lung cancer (NSCLC) Efficacy of adjuvant therapy after resection (lobectomy or pneumonectomy)
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Data from the KEYNOTE-091 study were presented at the European Society for Medical Oncology (ESMO) Virtual Plenary and will be discussed with global drug regulators
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According to data from the World Health Organization, there will be about 816,000 new lung cancer cases and about 715,000 deaths in China in 2020[i]
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Studies have shown that even after complete tumor resection, patients with non-small cell lung cancer still have the risk of postoperative recurrence, metastasis and second primary lung cancer, and more than 50% of tumor recurrence or metastasis occurred in the first 2 years after surgery[ ii]-[iii]
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Postoperative adjuvant therapy is an important treatment component for reducing recurrence, prolonging survival and improving quality of life after complete resection of early and mid-stage non-small cell lung cancer, which can bring more clinical benefits to patients[iii]
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"KEYNOTE-091 is the first study of pembrolizumab in the adjuvant treatment of NSCLC patients, and one of the pivotal studies of pembrolizumab in patients with early-stage cancer and published data
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" Senior Associate, Global Clinical Research, Merck Laboratories President and Chief Medical Officer Dr.
Roy Baynes said, "We sincerely thank the patients and their families who participated in the study, as well as all the investigators.

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KEYNOTE-091 is a randomized, triple-blind, phase III trial evaluating pembrolizumab, versus placebo, with or without adjuvant chemotherapy as surgical resection (lobectomy or pneumonectomy) Differences in the efficacy and safety of adjuvant therapy in patients with post-IB-IIIA (AJCC 7th edition TNM staging criteria) non-small cell lung cancer
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The primary endpoint of the study was the overall population and the population with high PD-L1 expression (TPS greater than or equal to 50%) disease-free survival (DFS)[iv]; secondary endpoints of the study include overall survival (OS), lung cancer-specific survival (LCSS)[v]
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The study was co-enrolled in stage IB-IIIA and achieved R0 resection of 1177 patients with NSCLC were randomized 1:1 to receive pembrolizumab (200 mg every 3 weeks, intravenous infusion for 1 year or up to 18 doses) or placebo
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"Lung cancer in early stages is easily treatable, and adjuvant therapy after surgery may also help reduce the risk of recurrence
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KEYNOTE-091 Co-Principal Investigator, Professor Mary O'Brien, Head of Pulmonary Department and Consultant Medical Oncologist at Royal Marsden Hospital, and Professor of Practice (Medical Oncology) at Imperial College London, said, "The immunotherapy announced this time for IB-IIIA Data on disease-free survival in adjuvant therapy for patients with stage NSCLC opened up the scene for our physicians
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"Despite significant progress in the treatment of metastatic NSCLC in recent years, there is still an unmet need for patients with early-stage cancer, and 43% of patients with early-stage cancer will experience disease recurrence after surgery
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" Professor Luis Paz-Ares, co-principal investigator of KEYNOTE-091 and director of the Department of Medical Oncology, Doce de Octubre University Hospital, Madrid, Spain, said, “The interim analysis data published by KEYNOTE-091 provides an opportunity for adjuvant therapy for patients with stage IB-IIIA non-small cell lung cancer.
new ideas
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In addition to KEYNOTE-091, Merck has several pivotal Phase III clinical trials evaluating pembrolizumab in patients with early-stage cancer, including: KEYNOTE-716 for patients with stage IIB and IIC melanoma; KEYNOTE-054 in patients with stage III melanoma; KEYNOTE-564 in patients with renal cell carcinoma; KEYNOTE-522 in patients with triple-negative breast cancer; and in patients with BCG-unresponsive high-risk non-muscle-invasive bladder cancer KEYNOTE-057[vi]
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Merck has an extensive clinical development program for lung cancer and is actively advancing multiple registration-supported studies, including studies for early-stage and novel combination therapy options
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Focus on early-stage non-small cell lung cancer Includes KEYNOTE-091, KEYNOTE-671, KEYNOTE-867, and KEYLYNK-012[vii]
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Up to now, the indications of pembrolizumab approved by the China National Medical Products Administration (NMPA) are: for the treatment of unresectable or metastatic melanoma that has failed first-line therapy; Epidermal growth factor receptor (EGFR) mutation-negative and anaplastic lymphoma kinase (ALK)-negative locally advanced or metastatic non-small cell lung cancer first-line Monotherapy; combination with pemetrexed and platinum-based chemotherapy for epidermal growth factor receptor (EGFR) gene mutation-negative and anaplastic lymphoma kinase (ALK)-negative metastatic non-squamous non-small cell lung cancer (NSCLC) First-line therapy; combination with carboplatin and paclitaxel is indicated for first-line treatment of patients with metastatic squamous non-small cell lung cancer (NSCLC); single agent is used as a single agent to evaluate tumor expression PD-L1 (Composite Positive Score ( Treatment of patients with locally advanced or metastatic esophageal squamous cell carcinoma (ESCC) who have failed prior first-line systemic therapy with a CPS ≥ 10); single agent is used as a single agent for the assessment of tumor expression by a well-validated assay for PD-L1 (combined positive) First-line treatment for patients with metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with CPS score (CPS) greater than or equal to 20; single agent for KRAS, NRAS and BRAF genes are wild-type, unresectable or First-line treatment of colorectal cancer (CRC) patients with metastatic hypermicrosatellite instability (MSI-H) or mismatch repair deficient (dMMR); combined platinum and fluorouracil chemotherapy for locally advanced unresectable or metastatic disease First-line treatment of patients with esophageal or gastroesophageal junction cancer
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The indication for pembrolizumab with or without adjuvant chemotherapy for postoperative adjuvant therapy in patients with stage IB to IIIA non-small cell lung cancer (NSCLC) has not been approved by the NMPA
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[i] IARC.
China Fact Sheet (2020).
[ii] Lou F, Huang J, Sima CS, et al.
Patterns of recurrence and second primary lung cancer in early–stage lung cancer survivors followed with routine computed tomography surveillance[J ].
J Thorac Cardiovasc Surg, 2013, 145(1):75–81; discussion 81–82.
DOI: 10.
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jtcvs.
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09.
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[iii] Lu Shun, Wu Yilong et al.
Guidelines for Adjuvant Treatment After Complete Resection of Cell Lung Cancer (2021 Edition)" Chinese Medical Journal, Volume 101, Issue 16, April 27, 2021 [iv] Here, DFS is defined as the time from randomization to disease recurrence and distant metastasis ( including second primary non-small cell lung cancer or other malignancies) or time of death from any cause, whichever occurs first
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[v] Here, LCSS is defined as the time from randomization to the date of death due to lung cancer [vi] Here, the indications for KEYNOTE-716, KEYNOTE-054, KEYNOTE-564, KEYNOTE-522, and KEYNOTE-057 None have been approved by the NMPA[vii] Here, none of the indications indicated by KEYNOTE-091, KEYNOTE-671, KEYNOTE-867 and KEYLYNK-012 have been approved by the NMPA