NSCLC, metastatic CheckMate 026: A phase 3 trial of nivolumab vs investigator's choice (IC) of platinum-based doublet chemotherapy (PT-DC) as first-line therapy for stage iv/recurrent programmed death ligand 1 (PD-L1)−positive NSCLC

Socinski, Mark A.; Creelan, Ben; Horn, Leora; Reck, Martin; Paz‐Ares, Luis; Steins, Martin; Felip, Enriqueta; Heuvel, Michel van den; Ciuleanu, Tudor-Eliade; Badin, Firas; Ready, Neal; Hiltermann, T Jeroen N; Nair, Suresh; Juergens, Rosalyn A.; Peters, Solange; Minenza, Elisa; Geese, William J.; Bhagavatheeswaran, Prabhu; Chen, A.; Carbone, David P.

doi:10.1093/annonc/mdw435.39

Cited by 107 publications

(126 citation statements)

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“…Since 2015, immunotherapy with PD-1 inhibitors has become a standard secondline treatment option that is superior to docetaxel [10][11][12] . In the keynote-024 trial, approximately 40% of the patients who initially received chemotherapy crossed over to immunotherapy, and in the CheckMate-026 trial, almost 60% of patients who progressed on first-line therapy received second-line therapy 12,46 . Those percentages far surpass the rate of second-line systemic therapy administration in our cohort and suggest that novel therapies have the potential to allow for continued sequential therapies in many patients with stage iv nsclc.…”

Section: Figurementioning

confidence: 99%

Reasons for Lack of Referral to Medical Oncology for Systemic Therapy in Stage Iv Non-small-cell Lung Cancer: Comparison of 2003–2006 with 2010–2011

Tudor

et al. 2017

Current Oncology

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Introduction Only approximately 25% of stage iv non-small-cell lung cancer (nsclc) patients receive systemic therapy. For such patients, we examined factors affecting referral to a cancer centre (cc) and to medical oncology (mo), and use of systemic therapy. were referred to a cc, with 22% and 23% receiving traditional chemotherapy (tctx). Referral to a cc or mo and use of tctx correlated with survival (p < 0.0001): The mos duration was 11.2 months in those receiving tctx and 1.0 months in those not referred to a cc. The overall mos duration was similar in the two cohorts (4.1 months vs. 3.9 months, p = 0.47). Major reasons for lack of referral to mo included poor functional status, rapid decline, and patient wish, which were similar to the reasons for forgoing tctx. In the two cohorts, 87 (9.4%) and 42 (7.5%) patients received epidermal growth factor inhibitors, with a mos duration of 16.2 months. Multivariable analysis showed that male sex [hazard ratio (hr): 1.16; p = 0.008] and pulmonary embolus (hr: 1.2; p = 0.002) correlated with worse survival. In contrast, receipt of chemotherapy (hr: 0.5; p < 0.001) and enrolment in a clinical trial (hr: 0.76; p = 0.049) correlated with better survival. Methods ConclusionsOur experience confirms that, over time, uptake of systemic therapy, including tctx and targeted therapy, changed little despite their established efficacy. Most of the factors limiting systemic therapy uptake appear to be non-modifiable at the time of referral. Rapid diagnosis and the availability of well-tolerated drugs for all nsclc patients will likely be the most important factors in increasing systemic therapy uptake in this population.

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Section: Figurementioning

confidence: 99%

Reasons for Lack of Referral to Medical Oncology for Systemic Therapy in Stage Iv Non-small-cell Lung Cancer: Comparison of 2003–2006 with 2010–2011

Tudor

et al. 2017

Current Oncology

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“…The companion diagnostic (PD-L1 IHC 22C3 pharmDx, Dako) linked to pembrolizumab has a cut-off of 50% PD-L1 expression whereas this is only 5% for the assay (PD-L1 IHC 28-8 pharmDx, Dako) linked to nivolumab. At the recent ESMO Congress in Copenhagen data with both immune checkpoint inhibitors was presented, and here, nivolumab, in the CheckMate 026 study, failed to demonstrate superiority over platinum based chemotherapy (22). Despite it is not possible to make a direct comparison between the two drug-diagnostic combination, a likely explanation for the failure of nivolumab is the lower assay cut-off value that allow a wider patient population to be treated with this drug.…”

Section: Drug-diagnostic Co-developmentmentioning

confidence: 86%

“…How critical it is to select the right cut-off has been demonstrated very recently with respect to the PD-1 immune checkpoint inhibitors pembrolizumab (Keytruda, Merck Sharp & Dohme) and nivolumab (Opdivo, BristolMyers Squibb) in relation to first-line treatment of advanced stage non-small cell lung cancer (NSCLC) (20)(21)(22). The companion diagnostic (PD-L1 IHC 22C3 pharmDx, Dako) linked to pembrolizumab has a cut-off of 50% PD-L1 expression whereas this is only 5% for the assay (PD-L1 IHC 28-8 pharmDx, Dako) linked to nivolumab.…”

Section: Drug-diagnostic Co-developmentmentioning

confidence: 99%

Companion diagnostics—a tool to improve pharmacotherapy

Jørgensen¹,

Hersom

2016

Ann. Transl. Med.

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The variability of pharmacotherapy can be of a significant magnitude, and the main reason for this is often diseases heterogeneity. Patients who have similar diagnoses very often respond differently to the same pharmacological intervention, with great variability in both efficacy and safety outcome. Despite having discussed personalized medicine for more than a decade, we still see that most drug prescriptions for severe chronic diseases are largely based on 'trial and error' and not on solid biomarker data. However, with the advance of molecular diagnostics and a subsequent increased understanding of disease mechanisms, things are slowly changing. Within the last few years, we have seen an increasing number of predictive biomarker assays being developed to guide the use of targeted cancer drugs. This type of assay is called companion diagnostics and is developed in parallel to the drug using the drug-diagnostic co-development model. The development of companion diagnostics is a relatively new discipline and in this review, different aspects will be discussed including clinical and regulatory issues.Furthermore, examples of drugs, such as the ALK and PD-1/PD-L1 inhibitors, that have been approved recently together with a companion or complimentary diagnostic will be given.

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“…Recently, the results of the Check-Mate 026 trial evaluating the efficacy of nivolumab in the first-line treatment in advanced-stage NSCLC patients have been published [24]. The study considered ≥1% as the cut-off value for PD-L1 positivity, and a total of 541 subjects were randomized 1:1 into nivolumab (3 mg/kg biweekly) or platinum-based chemotherapy groups.…”

Section: Nivolumabmentioning

confidence: 99%

“…It was concluded that there were no differences between the two arms in terms of PFS [4.2 months vs. 5.9 months, hazard ratio (HR): 1.15] or median OS (14.4 months vs. 13.2 months, HR: 1.02) ( Table 1). However, the high rate of crossover to nivolumab on the chemotherapy arm, the higher overall survival rates in the chemotherapy arm than in historical controls, a greater proportion of Asian patients included in the study, and patients with a broad range of PD-L1 expression (≥1%) might have affected the results [24].…”

Section: Nivolumabmentioning

confidence: 99%

Immune Checkpoint Inhibitors in Advanced-Stage Non-small Cell Lung Cancer

Kazaz

Öztop

2017

Turk Thorac J

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More than half of non-small cell lung cancer (NSCLC) patients are at an advanced stage at the time of diagnosis, and they have a poor prognosis. Systemic treatment is the basic treatment approach for advanced-stage NSCLC, and chemotherapy and targeted treatments are commonly used based on the molecular characteristics. Although targeted therapies have led to a significant level of improvement in terms of survival, the results are still unsatisfactory. However, considerable attention has been focused to the immunotherapy with recent positive results reported by studies on this field. In this context, a certain portion of clinical studies have shown dramatic results, and these have involved inhibitors developed particularly against the immune checkpoint protein programmed death receptor-1 and its ligand (programmed death ligand-1). This review aims to present the significance of immune checkpoint inhibitors in NSCLC and to summarize the findings of relevant contemporary clinical studies. KEYWORDS: Non-small cell lung cancer, immunotherapy, checkpoint inhibitors INTRODUCTIONLung cancer is the leading cause of cancer-related death for both genders worldwide and poses a serious public health problem [1,2]. Non-small cell lung cancer (NSCLC) comprises approximately 85% of all lung cancers. More than 50% of NSCLC patients are at an advanced stage at the time of diagnosis, and they are characterized by a poor prognosis. In addition, 40-70% of the early stage NSCLC patients develop distant metastases throughout the course of the disease, despite curative surgical intervention [3][4][5]. Systemic treatment is the basic treatment approach for advanced-stage NSCLC; some patients receive radiotherapy if needed, and other specific patients may undergo surgical intervention. With regard to the planning of systemic treatment, the decision is made by taking patient-and tumor-related factors into account. Primary patient-related factors include age, performance status, and comorbidity, and main tumor-related factors include classification of the histological type and molecular analysis of the tumor, which are of key importance [6,7]. Today, recommended molecular analyses are epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) fusion oncogene and C-ros oncogene 1 analyses. After performing these analyses, relevant patients receive targeted treatments (erlotinib, gefitinib, afatinib, or crizotinib), while others are treated with systemic chemotherapy. These approaches extend the survival time and increase the quality of life. In addition, there are recent studies available on the BRAF, RAS, and MET pathways, all of which have reported considerably positive findings [8][9][10]. The agents targeting these pathways may be used in this field in the near future.Recently, we have witnessed a key development in the field of immunotherapy for the treatment of NSCLC. A better identification of the immune pathways playing a role in tumor progression and growth in lung cancer, which is known to have a relativ...

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NSCLC, metastatic CheckMate 026: A phase 3 trial of nivolumab vs investigator's choice (IC) of platinum-based doublet chemotherapy (PT-DC) as first-line therapy for stage iv/recurrent programmed death ligand 1 (PD-L1)−positive NSCLC

Cited by 107 publications

References 0 publications

Reasons for Lack of Referral to Medical Oncology for Systemic Therapy in Stage Iv Non-small-cell Lung Cancer: Comparison of 2003–2006 with 2010–2011

Reasons for Lack of Referral to Medical Oncology for Systemic Therapy in Stage Iv Non-small-cell Lung Cancer: Comparison of 2003–2006 with 2010–2011

Companion diagnostics—a tool to improve pharmacotherapy

Immune Checkpoint Inhibitors in Advanced-Stage Non-small Cell Lung Cancer

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