KEYNOTE-189 ist eine wichtige Phase-III-Studie zur Immuntherapie des nichtkleinzelligen Bronchialkarzinoms (NSCLC), die am AACR-Kongress als Highlight präsentiert und zeitgleich im New England Journal of Medicine publiziert wurde KEYNOTE-189 trial is provided in the Supplementary Appendix, available at NEJM.org. This article was published on April 16, 2018, at NEJM.org. N Engl J Med 2018;378:2078-92. DOI: 10.1056/NEJMoa180100 KEYNOTE-189: Updated Overall Survival and Progression After the Next Line of Therapy With Pembrolizumab plus Chemotherapy With Pemetrexed and Platinum vs Placebo plus Chemotherapy for Metastatic Nonsquamous Non-Small-Cell Lung Cancer. Study Design, Participants and Treatment AUC, area under the concentration-time curve; ECOG PS, Eastern Cooperative Oncology Group performance status; PD.
We report an updated analysis from KEYNOTE-189 (ClinicalTrials.gov: NCT02578680). Methods: Patients were randomly assigned (2:1) to receive pemetrexed and platinum plus pembrolizumab (n = 410) or placebo (n = 206) every 3 weeks for 4 cycles, then pemetrexed maintenance plus pembrolizumab or placebo for up to a total of 35 cycles. Eligible patients with disease progression in the placebo. double-blind, phase III KEYNOTE-189 study conducted with a median follow-up of 10.5 months, pembrolizumab plus pemetrexed-platinum signiﬁcantly improved overall survival(OS;hazardratio[HR],0.49;95%CI,0.38to0.64; P , .001), progression-free survival (PFS; HR, 0.52; 95%CI,0.43to0.64; P,.001),andobjectiveresponse rate (ORR; 47.6% v 18.9%; P , .001) compared with placebo plus pemetrexed-platinum. Study design and participants. KEYNOTE-189, a multicentre, double-blind, randomised, placebo-controlled, phase 3 study, was done at 126 cancer centres in 16 countries. Detailed methods and primary results for KEYNOTE-189 have been reported elsewhere. 5. Gandhi L ; Rodríguez-Abreu D ; Gadgeel S ; et al. Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer. N Engl J Med. Background. In the phase 3 KEYNOTE-189 study (NCT02578680), pembrolizumab plus pemetrexed and platinum-based chemotherapy (pemetrexed-platinum) significantly improved overall survival (OS) and progression-free survival (PFS) in patients with previously untreated metastatic nonsquamous NSCLC versus placebo plus pemetrexed-platinum Trial Design and Treatment . In this double-blind trial, patients were randomly assigned, in a 2:1 ratio, to receive either 200 mg of pembrolizumab or saline placebo, both administered.
KEYNOTE-189 study design 1,2,4 The phase III KEYNOTE-189 study included patients with all PD-L1 levels After initial therapy, ALIMTA and KEYTRUDA were continued until disease progression or unacceptable toxicity (or up to.. KEYNOTE-189 study design 1: Phase 3, randomized, multicenter, double-blind, active-controlled trial in systemic therapy-naïve patients with metastatic nonsquamous NSCLC, regardless of PD-L1 tumor expression status and with no EGFR or ALK genomic tumor aberrations. Patients with autoimmune disease that required systemic therapy within 2 years of treatment; a medical condition that required. KEYNOTE-189 Study Design. KEYNOTE-189 Updated Efficacy Findings. KEYNOTE-189 Overall Survival by PD-L1 Expression. KEYNOTE-189 Summary of AEs. IMpower130. IMpower150Phase 3 Study of Atezolizumab With Standard Bevacizumab + Chemotherapy . KEYNOTE-407. CheckMate 227Study Design. CheckMate 227Efficacy Findings in Part 1a (PD-L1 ≥ 1%) CheckMate 227Efficacy Findings in Part 1b (PD-L1 < 1%) CCTG. First-Line KEYNOTE 189 Study Design (Non-Squamous Platinum/Pemetrexed + Pembrolizumab) and KEYNOTE-407: Study Design (Squamous) KEYNOTE 189 (Non-Squamous Platinum/Pemetrexed + Pembrolizumab): OS. KEYNOTE 189 (Chemo + Pembrolizumab): OS subsets. KEYNOTE-407: OS in ITT Population (Squamous) IMpower150 Study Design . IMpower150: Interim OS in ITT WT Population. IMpower150: Interim OS in EGFR/ALK+. KEYNOTE-189 study design 1. The original analysis 1. A randomised, multicentre, double-blind, active-controlled, phase 3 trial in patients (n=616) with previously untreated metastatic non-squamous NSCLC with no EGFR or ALK positive mutations. 1. 616 patients were randomly assigned (in a 2:1 ratio) to receive pemetrexed and a platinum-based drug plus either 200 mg of pembrolizumab (n=410) or.
The KEYNOTE-189 study showed that first-line treatment with pembrolizumab plus platinum-doublet chemotherapy significantly prolonged overall survival and progression-free survival compared with chemotherapy alone, irrespective of PD-L1 TPS, in patients with non-squamous non-small-cell lung cancer. The KEYNOTE-407 study demonstrated similar findings in patients with squamous non-small-cell lung. The results of KEYNOTE-189 and KEYNOTE-407 showed that OS has significant benefits regardless of PD-L1 expression. 107,108 However, other studies have put forward different opinions that NSCLC patients with low or no expression of PD-L1 can also benefit from anti-PD-1 treatment. 109 A similar phenomenon also occurs in other tumor types such as gastric cancer, renal cell carcinoma and. KEYNOTE-158 STUDY DESIGN The efficacy of KEYTRUDA was investigated in a prospectively planned retrospective analysis of KEYNOTE-158, a multicenter, nonrandomized, open-label trial. The trial excluded patients who previously received an anti-PD-1 or other immune-modulating monoclonal antibody, had an autoimmune disease, or had a medical condition that required immunosuppression. Tumor status. In KEYNOTE-189 wurden Patienten unabhängig vom PD-L1-Status, aber mit Chemoimmuntherapie behandelt, allerdings nur Patienten mit nichtplattenepithelialen Tumoren: Aus dieser Studie haben wir bereits den Schluss gezogen, dass alle Patienten profitieren und dementsprechend eine Chemoimmuntherapie (Pemetrexed+Pembrolizumab) erhalten sollen. Die Ergebnisse haben auch zu einer beschleunigten. IMpower150 Study Design. Fig. 2. INV-Assessed PFS in ITT-WT (Arm B vs. Arm C) The available data so far suggest that the addition of cytotoxic chemotherapy to a checkpoint inhibitor can enhance or modulate the effects of anti-PD-1/- PD-L1 inhibitors. This is now supported by the results of KEYNOTE-021, cohort G and IMpower150. There are a number of other phase III studies using a similar.
The Keynote 189 study randomly assigned 616 patients with in EGFR-mutated NSCLC was terminated early due to a high rate of interstitial pneumonitis. 51, 52 We await an improved study design with a good rationale for combined targeted therapy and immunotherapy in NSCLC. There remain many unresolved issues on treatment, including combination therapy for selected or all patients. The. KEYNOTE-598 Study Design and Additional Data (Late-Breaking Abstract #PS01.09) In KEYNOTE-189, when KEYTRUDA was administered with pemetrexed and platinum chemotherapy in metastatic nonsquamous NSCLC, KEYTRUDA was discontinued due to adverse reactions in 20% of 405 patients. The most common adverse reactions resulting in permanent discontinuation of KEYTRUDA were pneumonitis (3%) and acute. KEYNOTE‐189 has been recently updated with 46.3 months' median follow‐up, and the OS (median 22.0 vs. 10.6 months; HR, 0.60) and PFS (median 9 vs. 4.9 months; HR, 0.50) remained significantly different in the intention‐to‐treat population despite 57% of patients in the placebo/chemotherapy arm receiving subsequent anti-PD‐(L)1 therapy. At 3 years, OS and PFS in the experimental. Therefore, other studies, such as the KEYNOTE-189 trial, 21 have explored the combination of immunotherapy and chemotherapy and demonstrated that this strategy can improve clinical outcomes compared with chemotherapy alone for first-line treatment, irrespective of PD-L1 expression. These results suggest that the combination of immunotherapy and chemotherapy can have a synergic effect in NSCLC. In KEYNOTE-189, when KEYTRUDA was administered with pemetrexed and platinum chemotherapy in metastatic nonsquamous NSCLC, KEYTRUDA was discontinued due to adverse reactions in 20% of 405 patients.
These differences in previously reported rates could be explained by heterogeneity in study design, follow-up time, event definition, and most importantly characteristics of the cohorts with regard to types of cancer and risk profiles of patients, which could confound the rates in highly selected cohorts. 15,16,18 Data on risk of ATE, which has been recently recognized to be also elevated in. KEYNOTE-189 (ClinicalTrials.gov identifier NCT02578680) KEYNOTE-040 (ClinicalTrials.gov identifier NCT02358031) was similar in design to CheckMate 141, a phase 3 study in platinum-failure, metastatic HNSCC comparing pembrolizumab with SOC chemotherapy (cetuximab, docetaxel, or methotrexate). There were 495 patients enrolled to the study across 20 countries. The safety of pembrolizumab was. The study schema is shown above. During the first data cutoff, a minimum of 7 months was required and at that time, the study met both primary endpoints of improving overall survival and PFS. 22% of patients are still on treatment in the pembro/axi arm compared with 17.9% in the sunitinib arm. For patients who discontinued treatment on trial, 54.5% of patients on pembro/axi received subsequent. Study design A systematic review of studies that reported clinical out-comes and toxicity associated with first-line therapy employing anti-PD1 or anti-PD-L1 antibodies alone or in combination with chemotherapy to treat metastatic, treatment-naïve NSCLC patients was performed. Search strategy The search for eligible studies was performed in Embase, Medline and Cochrane Library, all from.
A trial looking at pembrolizumab and chemotherapy for non small cell lung cancer (KEYNOTE 189) Please note - this trial is no longer recruiting patients. We hope to add results when they are available The following study design is for the JMDB trial. Patients were randomized to two treatment groups. In the ALIMTA versus ALIMTA with platinum chemotherapy + placebo for initial treatment (KEYNOTE-189), respectively, were nausea (56% vs 52%); fatigue (56% vs 58%); constipation (35% vs 32%); diarrhea (31% vs 21%); decreased appetite (28% vs 30%); rash (25% vs 17%); vomiting (24% vs 23%. a At data cutoff, 18/39 pts were alive and had not experienced PD per investigator assessment. b 7 patients died due to PD; 2 did not receive any additional treatment.. Conclusions. Pembro continues to show improvements in OS vs chemo as 1L treatment for metastatic NSCLC with PD-L1 TPS ≥50%. Despite the high crossover rate, 5-year OS was approximately doubled among pts who received pembro. ・keynote-189試験. asco2018の数週間前に公表された、キイトルーダ＋化学療法に関するkeynote-189試験のデータは、非扁平上皮がんでこのレジメンを「真の意味で」比較対照に設定した。異なる臨床試験の比較にはリスクがあるが、osのハザード比はキイトルーダ. And the fact that KEYNOTE-189 showed a survival endpoint was really a big plus. And I think the other power in this study was that it was so much bigger. And so, we're able to look at PD-L1.
In KEYNOTE-189, patients with metastatic non-squamous NSCLC, PS 0-1, without sensitising EGFR or ALK mutations, were randomised to receive pemetrexed and cisplatin or carboplatin plus either 200 mg of pembrolizumab or placebo every 3 weeks for 4 cycles, followed by pembrolizumab or placebo for up to a total of 35 cycles plus pemetrexed maintenance therapy KEYNOTE-048 was an open-label, randomized phase 3 study of P or P + chemotherapy (C) vs EXTREME (E) as first-line systemic therapy for R/M HNSCC (NCT02358031). Methods. Patients (pts) with R/M HNSCC not curable by local therapy and with no prior systemic therapy (R/M setting) who provided a tumor sample for PD-L1 testing were randomized to P 200 mg Q3W, P + C (cisplatin 100 mg/m2 or. Background: In the phase 3 KEYNOTE-189 study (NCT02578680), pembrolizumab plus pemetrexed and platinum-based chemotherapy (pemetrexed-platinum) significantly improved overall survival (OS) and. trials with straightforward study designs and easily interpretable endpoints CONTRIBUTORS Gideon Blumenthal U.S. Food and Drug Administration Jonathan Cheng Merck & Co., Inc. Katherine Couvillon Patient Advocate Jennifer Gao U.S. Food and Drug Administration Karen Jones Genentech, A Member of the Roche Group Robert Kester Merck & Co., Inc. Scott Korn Merck & Co., Inc. Qi Liu U.S. Food and Drug. The adjuvant study is designed to determine if treatment et al. Interleukin-1β inhibition and the prevention of recurrent cardiovascular events: rationale and design of the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS). Am Heart J. 2011;162:597-605. Lu H, Ouyang W, Huang C. Inflammation, a key event in cancer development. Mol Cancer Res. 2006;4(4):221-233. World.
Findings from the pivotal Phase III KEYNOTE-189 study showed that using pembrolizumab in combination with the antimetabolite pemetrexed (Alimta; Eli Lilly) and a platinum-based agent such as cisplatin or carboplatin significantly improved overall survival, decreasing the risk of death by >50% compared with the use of chemotherapy alone . A main disadvantage is that it requires extracellular surface expression of the targets on the tumor cells, and this limits CAR-T cells' specificity and.
. Fourth, irAEs are sometimes difficult to differentiate from infections such as pneumonitis. Last, a small sample size also limited our ability to fully evaluate the impact of CPI on outcomes, especially on mortality. In conclusion, patients with advanced lung cancer treated. Tsao pointed out that close to one-half of the patients enrolled in the study had a PD-L1 TPS of 50% of greater -- higher than what is typically seen -- 20% to 30%. These were the patients that.
Studies on chemoradiotherapy and simultaneous immune check-point inhibition Rutgers (NCT02621398) This multicentre, non-randomised phase I trial using a 3 plus 3 design assessed the safety of timing and dosing of pembrolizumab sequentially and concurrently with taxane-platinum combination definitive photon/proton-based CRT to a dose of 60 Gy. For the first time, this Phase 3 study shows superior PFS with first-line combination immunotherapy in a predefined population of NSCLC patients with high TMB, said Matthew D. Hellmann, M.D., study investigator and medical oncologist at Memorial Sloan Kettering Cancer Center. CheckMate -227 showed that TMB is an important, independent predictive biomarker that can identify a population.
A blood-based DNA sequencing assay to infer tumor mutational burden in the absence of tumor biopsy predicts response to PD-L1 blockade in patients with non-small-cell lung cancer Treatment of lung cancer refers to the use of medical therapies, such as surgery, radiation, chemotherapy, immunotherapy, percutaneous ablation, and palliative care, alone or in combination, in an attempt to cure or lessen the adverse impact of malignant neoplasms originating in lung tissue.. Lung cancer is an extremely heterogeneous family of malignant neoplasms, and well over 50 different. Background: In the absence of head-to-head trials, this study indirectly compared the effectiveness of pembrolizumab + chemotherapy vs nivolumab + ipilimumab for the first-line treatment of metastatic stage IV NSCLC patients with PD-L1 tumor proportion score (TPS) ≥1%. Methods: An anchored matching-adjusted indirect comparison (MAIC) was conducted using pooled individual patient data (IPD. This study describes a new statistical method to identify genes associated with cancer heritability in the broader population, creating a map of the heritable cancer genome with gene-level resolution. Tumor Biology and Immunology. Acute Kidney Injury Instigates Malignant Renal Cell Carcinoma via CXCR2 in Mice with Inactivated Trp53 and Pten in Proximal Tubular Kidney Epithelial Cells. Xunian. Lung cancer remains a leading cause of cancer-related mortality worldwide with the poor prognosis. Encouragingly, immune checkpoint blockade targeting programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) has dramatically changed the landscape for treatments in patients with non-small-cell lung cancer (NSCLC). However, only a small proportion of NSCLC patients responded to.
Clinical studies support the efficacy of programmed cell death 1 (PD-1) targeted therapy in a subset of patients with metastatic gastric cancer (mGC). With the goal of identifying determinants of. Study design: References: L755S: 19: ILC IDC MDC: TKD, C- α helix: Activation: Trastuzumab/lapatinib resistance Neratinib/afatinib sensitivity: Breast cancer HER2+ patients, in vitro studies [40, 41] Lapatinib resistance: Breast cancer HER2+ patients, in vitro studies [42, 43] Trastuzumab resistance Afatinib/neratinib sensitivity: MANO method and xenograft : Afatinib/neratinib sensitivity. Study design and data sources. This was a retrospective, observational, descriptive study of adult patients with advanced NSCLC who initiated 1L treatment with systemic chemotherapy, targeted therapies, or IO-based regimens between March 1, 2015, and August 1, 2018, within the US Oncology Network (USON). Initiation of 1L treatment was considered the index event, and eligible patients were. Background Immune-checkpoint inhibitors plus chemotherapy are emerging as effective first-line treatment in advanced non-small-cell lung carcinoma (NSCLC), but little is known about the magnitude of benefits and potential clinical predictors. Methods We performed a meta-analysis of randomized trials that compared PD-1/PD-L1 inhibitor plus chemotherapy with chemotherapy in first line of.
Pembrolizumab, sold under the brand name Keytruda, is a humanized antibody used in cancer immunotherapy.This includes to treat melanoma, lung cancer, head and neck cancer, Hodgkin lymphoma, and stomach cancer. It is given by slow injection into a vein.. Common side effects include fatigue, musculoskeletal pain, decreased appetite, itchy skin (pruritus), diarrhea, nausea, rash, fever (pyrexia. Designing Better Characteristics for Potentially Enhanced Clinical Benefit Drug Design Attributes Drug antibody ratio Payload Payload Membrane permeability Notes: T-DM1 = trastuzumab emtansine; DS-8201 = trastuzumab deruxtecan Validated topo-1 mechanism Sources: (1) Daiichi Sankyo's R&D Day December 2018, (2) T-DM1 FDA label and (3) Ogitani et al, 2016, Cancer Science for DS-8201 Bystander. This result was in agreement with a phase I study of pembrolizumab in Japanese patients.14 KEYNOTE-189 did not conduct a China extension study, but the results in KEYNOTE-042 China extension study (NCT03850444)15 and KEYNOTE-407 China extension study (NCT03875092)16 for patients with locally advanced/metastatic NSCLC showed that the clinical outcomes and safety profile are consistent with.
Importantly, recent data from the large randomized double-bind phase III study Keynote 189 Study design. The aim of this study was to assess the immunomodulatory potential of PARPi, their ability to trigger specific cancer cell-associated immune responses, and their potential to enhance cancer cell immunogenicity through cell-autonomous mechanisms. Our prespecified hypothesis was that. So, really very similar to the KEYNOTE-189 trial except in a squamous population with a different chemotherapy backbone. And the trial results looked, I would say, every bit as impressive as. Trial Design and New Data from KEYNOTE-146/Study 111 (Abstract #994O) In KEYNOTE-189, when KEYTRUDA was administered with pemetrexed and platinum chemotherapy in metastatic nonsquamous NSCLC, KEYTRUDA was discontinued due to adverse reactions in 20% of 405 patients. The most common adverse reactions resulting in permanent discontinuation of KEYTRUDA were pneumonitis (3%) and acute kidney. However, the KEYNOTE-024 trail (first line pembrolizumab) and the KEYNOTE-189 trial (pembrolizumab + pemetrexed & platinum) showed superior OS in all subgroups, even in the group of patients with brain metastasis [8, 17]. This makes ICI therapy a therapeutic option with the need of future prospective trials in patients with active brain metastasis. In a recently published Phase II study in. CT043 - Outcomes among patients (pts) with metastatic nonsquamous NSCLC with liver metastases or brain metastases treated with pembrolizumab (pembro) plus pemetrexed-platinum: Results from the KEYNOTE-189 study. Cancer Res 2019; 79 (13 Suppl): CT043. DOI: 10.1158/1538-7445.AM2019-CT043
Trial Design and New Data for Study 111/KEYNOTE-146 . Study 111/KEYNOTE-146 is a multi-center, open-label, single-arm, Phase 1b/2 basket trial (ClinicalTrials.gov, NCT02501096) evaluating the combination of LENVIMA (20 mg/day) with KEYTRUDA (200 mg intravenously every three weeks) in patients with selected solid tumors (metastatic endometrial cancer, metastatic head and neck cancer, metastatic. Expanding this same design to patients with PD-L1 TPS ≥ 1 One study found that 7%-13% of NSCLC patients treated with PD-1 axis inhibitors experienced grade 3 or higher toxicities; the incidence of high-grade irAEs among patients with all tumor types treated with PD-1 and PD-L1 inhibitors is thought to be less than 20% . In clinical trials, up to 2% of patients treated with these agents. In one study focused on NSCLC patient preferences for chemotherapies, Survey design best practices 20 were employed to develop the survey instrument, which consisted of four modules: eligibility screener and treatment history, health-related quality of life (HRQoL), DCE preference elicitation, and demographics. DCEs are widely used in health economics to measure stakeholder preferences for.
Cancer immunotherapy has proven remarkably successful through instigation of systemic antitumor T cell responses. Despite this achievement, further advancements are needed to expand the scope of susceptible cancer types and overcome variation in treatment outcomes between patients. Small-molecule drugs targeting defined pathways and/or cells capable of immune modulation are expected to. Immunotherapy for non-small cell lung cancer (NSCLC) is incorporated increasingly in first line treatments protocols. Multiple phase 3 studies have tested different medications targeting programmed death receptor 1 (PD-1), programmed death-ligand 1 (PD-L1), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), with or without chemotherapy. The inclusion criteria differ between the various.
Another limitation of this study was the open-label design, although this was unlikely to have affected the outcomes owing to response assessment by blinded independent central review. While additional follow-up from the phase 3 KEYNOTE-189 study will provide more robust long-term data and evaluate the benefit of pembrolizumab plus chemotherapy in this population, this analysis contains the. Gastrointestinal (GI) malignant neoplasms have a high global incidence and treatment prospects for patients with advanced GI tumors are dismal. PD-1/PD-L1 inhibitors emerged as a frontline treatment for several types of cancer. However, the shortcomings of PD-1/PD-L1 inhibitors have been observed, including low objective response rates and acquired tumor resistance, especially in patients. The National Lung Screening Trial: overview and study design. Radiology, 2011, 258(1): 243-253. ABERLE DR, ADAMS AM, BERG CD, et al. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med, 2011, 365(5): 395-409. ABERLE DR, ADAMS AM, BERG CD, et al. Baseline characteristics of participants in the randomized national lung screening trial. J Natl Cancer.
Results from the first trial, KEYNOTE-189, showed that adding the checkpoint inhibitor pembrolizumab to chemotherapy significantly improved overall survival, and results from the second trial, CheckMate-227, showed that patients who received two checkpoint inhibitors—nivolumab plus ipilimumab—had significantly longer progression-free survival compared with those who received chemotherapy. Another clinical trial with a similar design to KEYNOTE-042 but only enrolling patients with TPS of 50% or more (KEYNOTE-024) was stopped early by an independent data and safety monitoring committee after demonstrating superiority of pembrolizumab compared with platinum-based chemotherapy with regard to PFS (10.3 vs. 6 months), despite a large percentage of patients in the chemotherapy arm. The study design was similar to that of KEYNOTE-024, except that patients had PD-L1 expression with a ≥ 1% TPS based on the PD-L1 IHC 22C3 pharmDx TM Kit. Patients were randomised (1:1) to receive pembrolizumab at a dose of 200 mg every 3 weeks (n=637) or investigator's choice platinum-containing chemotherapy (n=637; including pemetrexed+carboplatin or paclitaxel+carboplatin. Patients with. Recent pivotal studies have assessed the role of immunotherapy in previously untreated metastatic NSCLCs in both squamous and nonsquamous histology, and 4 studies have shown an OS benefit from adding PD-1 or PD-L1 inhibitor to standard chemotherapy (KEYNOTE-189, IMpower150, IMpower130, KEYNOTE-407). Chemotherapy-sparing regimens such as PD-1 or PD-L1 inhibitor alone or in combination with a. Study Design and Statistical Methods. This study was designed as a randomized Phase III trial to demonstrate the non-inferiority of TC compared with standard TP using overall survival as the primary endpoint. Patients are randomized to each treatment arm by a minimization method with institution, PS (0, 1 or 2), histology (squamous cell carcinoma or adenocarcinoma) and tumor sites (all of them.
Recent studies have extended systems to perform staging by assessing tumor extent and multifocality in breast MRI, 21 to a single region of a tumor. The predictive value of PD-L1 expression also may be limited. For example, in the KEYNOTE-189 clinical trial, immunotherapy with pembrolizumab in combination with standard chemotherapy produced a survival benefit in all patients regardless of. Background: In the phase 3 KEYNOTE-189 study (NCT02578680), pembrolizumab plus pemetrexed and platinum-based chemotherapy (pemetrexed-platinum) significantly improved overall survival (OS) and progression-free survival (PFS) in patients with previously untreated metastatic nonsquamous NSCLC versus placebo plus pemetrexed-platinum. We report updated efficacy outcomes from the protocol-specified. Updated Analysis From KEYNOTE-189: Pembrolizumab or Placebo Plus Pemetrexed and Platinum for Previously Untreated Metastatic Nonsquamous Non-Small-Cell Lung Cancer. J Clin Oncol. 2020 May.38(14):1505-1517. Pubmedid: 32150489. Puri S, Saltos A, Perez B, Le X, Gray JE. Locally Advanced, Unresectable Non-Small Cell Lung Cancer. Curr Oncol Rep. This study did not find any differences in sex, but this could also be due to the restriction of the cohort to those patients whose disease had advanced, or due to the non-comparative design of previous studies, which may limit their interpretation [27, 28, 46] The safety of KEYTRUDA in combination with pemetrexed and investigator's choice of platinum (either carboplatin or cisplatin) was investigated in KEYNOTE-189, a multicenter, double-blind, randomized (2:1), active-controlled trial in patients with previously untreated, metastatic nonsquamous NSCLC with no EGFR or ALK genomic tumor aberrations [see Clinical Studies (14.2)]. A total of 607.