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

doi:10.1016/S0140-6736(18)32409-7

The Lancet

Volume 393, Issue 10183, 4–10 May 2019, Pages 1819-1830

https://doi.org/10.1016/S0140-6736(18)32409-7 Get rights and content

Summary

Background

First-line pembrolizumab monotherapy improves overall and progression-free survival in patients with untreated metastatic non-small-cell lung cancer with a programmed death ligand 1 (PD-L1) tumour proportion score (TPS) of 50% or greater. We investigated overall survival after treatment with pembrolizumab monotherapy in patients with a PD-L1 TPS of 1% or greater.

Methods

This randomised, open-label, phase 3 study was done in 213 medical centres in 32 countries. Eligible patients were adults (≥18 years) with previously untreated locally advanced or metastatic non-small-cell lung cancer without a sensitising EGFR mutation or ALK translocation and with an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1, life expectancy 3 months or longer, and a PD-L1 TPS of 1% or greater. Randomisation was computer generated, accessed via an interactive voice-response and integrated web-response system, and stratified by region of enrolment (east Asia vs rest of world), ECOG performance status score (0 vs 1), histology (squamous vs non-squamous), and PD-L1 TPS (≥50% vs 1–49%). Enrolled patients were randomly assigned 1:1 in blocks of four per stratum to receive pembrolizumab 200 mg every 3 weeks for up to 35 cycles or the investigator's choice of platinum-based chemotherapy for four to six cycles. Primary endpoints were overall survival in patients with a TPS of 50% or greater, 20% or greater, and 1% or greater (one-sided significance thresholds, p=0·0122, p=0·0120, and p=0·0124, respectively) in the intention-to-treat population, assessed sequentially if the previous findings were significant. This study is registered at ClinicalTrials.gov, number NCT02220894.

Findings

From Dec 19, 2014, to March 6, 2017, 1274 patients (902 men, 372 women, median age 63 years [IQR 57–69]) with a PD-L1 TPS of 1% or greater were allocated to pembrolizumab (n=637) or chemotherapy (n=637) and included in the intention-to-treat population. 599 (47%) had a TPS of 50% or greater and 818 patients (64%) had a TPS of 20% or greater. As of Feb 26, 2018, median follow-up was 12·8 months. Overall survival was significantly longer in the pembrolizumab group than in the chemotherapy group in all three TPS populations (≥50% hazard ratio 0·69, 95% CI 0·56–0·85, p=0·0003; ≥20% 0·77, 0·64–0·92, p=0·0020, and ≥1% 0·81, 0·71–0·93, p=0·0018). The median surival values by TPS population were 20·0 months (95% CI 15·4–24·9) for pembrolizumab versus 12·2 months (10·4–14·2) for chemotherapy, 17·7 months (15·3–22·1) versus 13·0 months (11·6–15·3), and 16·7 months (13·9–19·7) versus 12·1 months (11·3–13·3), respectively. Treatment-related adverse events of grade 3 or worse occurred in 113 (18%) of 636 treated patients in the pembrolizumab group and in 252 (41%) of 615 in the chemotherapy group and led to death in 13 (2%) and 14 (2%) patients, respectively.

Interpretation

The benefit-to-risk profile suggests that pembrolizumab monotherapy can be extended as first-line therapy to patients with locally advanced or metastatic non-small-cell lung cancer without sensitising EGFR or ALK alterations and with low PD-L1 TPS.

Funding

Merck Sharp & Dohme.

Introduction

The ultimate objective of treating advanced non-small-cell lung cancer is to improve overall survival and quality of life. Before the availability of molecularly targeted therapy, advanced non-small-cell lung cancer was treated with chemotherapy, which is associated with a median survival of approximately 12 months¹ and has a poor adverse event profile. Targeted therapies have become standard first-line therapy for patients with driver oncogenes. Median survival in phase 3 trials ranged from 18·6 months to 30·5 months for tyrosine-kinase inhibitors targeting EGFR mutations2, 3, 4 and extends beyond 4 years for those targeting ALK alterations.5, 6, 7 For patients without driver oncogenes, however, improvements in survival were minimal until immunotherapeutic options became available.

Research in context

Evidence before this study

We searched PubMed on June 15, 2018, with the term “PD-1 OR PD-L1 OR MK-3475 OR pembrolizumab OR Keytruda OR BMS-936558 OR nivolumab OR Opdivo OR MPDL3280A OR atezolizumab OR Tecentriq OR MEDI4736 OR durvalumab OR Imfinzi OR MSB0010718C OR avelumab OR Bavencio AND metastatic AND first line OR previously untreated AND non-small cell lung cancer OR NSCLC.” We also used this term to search the abstracts from the 2017 and 2018 American Society of Clinical Oncology annual meetings and the 2016 and 2017 European Society for Medical Oncology congresses to identify results of clinical trials not yet published in full. We applied no other search parameters. We identified several randomised, phase 3 studies of patients with metastatic non-small-cell lung cancer treated with antibodies against programmed death protein 1 (PD-1) or its ligand PD-L1. The KEYNOTE-024 study showed significantly longer progression-free and overall survival with pembrolizumab monotherapy than with platinum-doublet chemotherapy in patients with a PD-L1 tumour proportion score (TPS) of 50% or greater. The CheckMate 026 study did not show improved overall survival with nivolumab monotherapy versus platinum-doublet chemotherapy in the primary population of patients with a PD-L1 expression level of 5% or greater. 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 cancer. The IMpower131 study of atezolizumab plus platinum-doublet chemotherapy showed significantly prolonged progression-free survival versus platinum-doublet chemotherapy alone in patients with squamous non-small-cell lung cancer, irrespective of PD-L1 expression. The IMpower150 study showed that the combination of atezolizumab, bevacizumab, and platinum-doublet chemotherapy significantly prolonged progression-free and overall survival in patients with non-squamous non-small-cell lung cancer, irrespective of PD-L1 expression or EGFR or ALK genetic alteration status. The CheckMate 227 study showed that nivolumab plus ipilimumab significantly prolonged progression-free survival versus platinum-doublet chemotherapy in patients with a high tumour mutational burden, irrespective of PD-L1 expression.

Added value of this study

The randomised phase 3 KEYNOTE-042 trial of pembrolizumab monotherapy versus chemotherapy as first-line treatment enrolled patients with locally advanced or metastatic non-small-cell lung cancer and a PD-L1 TPS of 1% or greater, expanding the population of patients compared with that assessed in the KEYNOTE-024 study. Overall survival was assessed as the primary endpoint, and we found a significant survival benefit in patients with PD-L1-positive tumours. The effect was greatest in patients with a TPS of 50% or greater, but remained significant in patients with a TPS of 1% or greater. Despite longer exposure to pembrolizumab treatment than to chemotherapy, the frequency of treatment-related adverse events, including those of grade 3 or worse, was lower in the pembrolizumab group.

Implications of all the available evidence

With our findings of a survival benefit and manageable safety profile for pembrolizumab monotherapy as first-line treatment in patients with PD-L1-positive, locally advanced or metastatic non-small-cell lung cancer, we suggest that use of this drug can be extended to previously untreated patients with a TPS as low as 1%. In the absence of direct prospective comparisons of pembrolizumab given alone and in combination with chemotherapy, patients with PD-L1-positive non-small-cell lung cancer should discuss the benefits and risks of each regimen with their physicians when choosing first-line therapy.

Pembrolizumab is a humanised IgG4 monoclonal antibody against programmed cell death protein 1 (PD-1). The phase 1 KEYNOTE-001⁸ and phase 2/3 KEYNOTE-010⁹ studies established the correlation between increased expression of the PD-1 ligand PD-L1 and benefit from treatment with pembrolizumab in patients with advanced non-small-cell lung cancer. KEYNOTE-02410, 11 was a phase 3 study that compared pembrolizumab monotherapy with platinum-based chemotherapy as first-line treatment in 305 patients with metastatic non-small-cell lung cancer and a PD-L1 tumour proportion score (TPS) of 50% or greater. The primary endpoint of progression-free survival and the key secondary endpoint of overall survival were significantly prolonged in the pembrolizumab group compared with in the standard chemotherapy group (median 10·3 months vs 6·0 months and 30·0 months vs 14·2 months, respectively).

In the international, randomised, open-label, phase 3 KEYNOTE-042 study, we compared pembrolizumab monotherapy with platinum-based chemotherapy as first-line therapy for patients with locally advanced or metastatic non-small-cell lung cancer and a PD-L1 TPS of 1% or greater. Here we report data from the second interim analysis.

Section snippets

Study design and patients

This randomised, open-label, phase 3 study was done at 213 sites in Argentina, Brazil, Bulgaria, Canada, Chile, China and Hong Kong Special Administrative Region, Colombia, Czech Republic, Estonia, Guatemala, Hungary, Japan, Latvia, Lithuania, Malaysia, Mexico, Peru, Philippines, Poland, Portugal, Romania, Russia, South Africa, South Korea, Sweden, Switzerland, Taiwan, Thailand, Turkey, Ukraine, and Vietnam. Patients were eligible for enrolment if they were aged 18 years or older, had locally

Results

3428 patients across all study sites were screened for enrolment (figure 1, appendix). 3019 had samples that were evaluable for PD-L1 expression, of whom 1978 (66%) had a TPS of 1% or greater, including 922 (31%) who had a TPS of 50% or greater. From Dec 19, 2014, to March 6, 2017, 1275 patients were randomly allocated to receive pembrolizumab (n=638) or chemotherapy (n=637). One patient in the pembrolizumab group was randomly assigned treatment after death and, therefore, the

Discussion

In this randomised phase 3 study of patients with previously untreated locally advanced or metastatic non-small-cell lung cancer without sensitising EGFR mutations or ALK translocations, pembrolizumab monotherapy significantly prolonged overall survival compared with standard chemotherapy in patients with a PD-L1 TPS of 50% or greater, 20% or greater, and 1% or greater. Pembrolizumab also had a better safety profile than chemotherapy.

Consistent with previous studies of pembrolizumab given as

Data sharing

Data will be available according to Merck Sharp & Dohme's data sharing policy, which, including restrictions, is available at http://engagezone.msd.com/ds_documentation.php. Requests for access to the clinical study data can be submitted through the EngageZone site or via email to [email protected].

References (27)

R Rosell et al.
Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial
Lancet Oncol
(2012)
JC Soria et al.
First-line ceritinib versus platinum-based chemotherapy in advanced ALK-rearranged non-small-cell lung cancer (ASCEND-4): a randomised, open-label, phase 3 study
Lancet
(2017)
RS Herbst et al.
Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial
Lancet
(2016)
J Goffin et al.
First-line systemic chemotherapy in the treatment of advanced non-small cell lung cancer: a systematic review
J Thorac Oncol
(2010)
RG Zinner et al.
PRONOUNCE: randomized, open-label, phase III study of first-line pemetrexed + carboplatin followed by maintenance pemetrexed versus paclitaxel + carboplatin + bevacizumab followed by maintenance bevacizumab in patients with advanced nonsquamous non-small-cell lung cancer
J Thorac Oncol
(2015)
JH Schiller et al.
Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer
N Engl J Med
(2002)
TS Mok et al.
Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma
N Engl J Med
(2009)
M Maemondo et al.
Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR
N Engl J Med
(2010)
BJ Solomon et al.
First-line crizotinib versus chemotherapy in ALK-positive lung cancer
N Engl J Med
(2014)
S Peters et al.
Alectinib versus crizotinib in untreated ALK-positive non-small-cell lung cancer
N Engl J Med
(2017)

EB Garon et al.

Pembrolizumab for the treatment of non-small-cell lung cancer

N Engl J Med

(2015)

M Reck et al.

Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer

N Engl J Med

(2016)

M Reck 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

J Clin Oncol

(2019)

Cited by (2320)

Deep learning radiomics model based on PET/CT predicts PD-L1 expression in non-small cell lung cancer
2024, European Journal of Radiology Open
Programmed cell death protein-1 ligand (PD-L1) is an important prognostic predictor for immunotherapy of non-small cell lung cancer (NSCLC). This study aimed to develop a non-invasive deep learning and radiomics model based on positron emission tomography and computed tomography (PET/CT) to predict PD-L1 expression in NSCLC.
A total of 136 patients with NSCLC between January 2021 and September 2022 were enrolled in this study. The patients were randomly divided into the training dataset and the validation dataset in a ratio of 7:3. Radiomics feature and deep learning feature were extracted from their PET/CT images. The Mann-whitney U-test, Least Absolute Shrinkage and Selection Operator algorithm and Spearman correlation analysis were used to select the top significant features. Then we developed a radiomics model, a deep learning model, and a fusion model based on the selected features. The performance of three models were compared by the area under the curve (AUC), sensitivity, specificity, accuracy, positive predictive value, and negative predictive value.
Of the patients, 42 patients were PD-L1 negative and 94 patients were PD-L1 positive. A total of 2446 radiomics features and 4096 deep learning features were extracted per patient. In the training dataset, the fusion model achieved a highest AUC (0.954, 95% confident internal [CI]: 0.890–0.986) compared with the radiomics model (0.829, 95%CI: 0.738–0.898) and the deep learning model (0.935, 95%CI: 0.865–0.975). In the validation dataset, the AUC of the fusion model (0.910, 95% CI: 0.779–0.977) was also higher than that of the radiomics model (0.785, 95% CI: 0.628–0.897) and the deep learning model (0.867, 95% CI: 0.724–0.952).
The PET/CT-based deep learning radiomics model can predict the PD-L1 expression accurately in NSCLC patients, and provides a non-invasive tool for clinicians to select positive PD-L1 patients.
Anlotinib may enhance the efficacy of anti-PD1 therapy by inhibiting the AKT pathway and promoting the apoptosis of CAFs in lung adenocarcinoma
2024, International Immunopharmacology
Although PD-1 inhibitors have revolutionized the treatment paradigm of non-small cell lung cancer (NSCLC), their efficacy in treating NSCLC has remained unsatisfactory. Targeting cancer-associated fibroblasts (CAFs) is a potential approach for improving the immunotherapy response. Multitarget antiangiogenic tyrosine kinase receptor inhibitors (TKIs) can enhance the efficacy of PD-1 inhibitors in NSCLC patients. However, the effects and mechanisms of antiangiogenic TKIs on CAFs have not been elucidated. In this study, we first compared anlotinib with other antiangiogenic TKIs and confirmed the superior efficacy of anlotinib. Furthermore, we established NSCLC-associated CAF models and found that anlotinib impaired CAF viability and migration capacity and contributed to CAF apoptosis and cell cycle arrest in the G2/M phase. Moreover, anlotinib treatment attenuated the capacity of CAFs to recruit lung cancer cells and macrophages. Experiments in animal models suggested that anlotinib could enhance the efficacy of anti-PD1 therapy in NSCLC and affect CAF proliferation and apoptosis. Anlotinib increased the abundance of tumor-infiltrating CD8 + T cells, and PD-1 inhibitor-induced cytotoxicity to tumor cells was achieved through the transformation of the tumor microenvironment (TME) caused by anlotinib, which may partly explain the synergistic antitumor effect of anlotinib and PD-1 inhibitors. Mechanistically, anlotinib affects CAF apoptosis and cell viability at least in part by inhibiting the AKT pathway. In conclusion, our study suggested that anlotinib could regulate the TME, inhibit the AKT pathway and promote CAF apoptosis, providing new insights into the antitumor effect of anlotinib and improving the efficacy of immunotherapy.
Prognostic impact of age in advanced non-small cell lung cancer patients undergoing first-line checkpoint inhibitor immunotherapy and chemotherapy treatment
2024, International Immunopharmacology
Research on the association between age and clinical outcome in patients with non-small cell lung cancer (NSCLC) treated with immunotherapy combined with chemotherapy as first-line setting is limited. The aim of study is to determine the influence of age on the progress-free survival (PFS) and overall survival (OS) in those patients after adjusting for potential confounders.
A total of 207 advanced NSCLC patients treated with immunotherapy combined with chemotherapy in the first-line treatment in Guangxi Medical University Cancer Hospital from March 10, 2019, to December 31, 2022, was retrospectively analyzed. χ2 (categorical variables) was used to analyze the differences among the different age groups. Cox regression and Kaplan–Meier analyses were used to assess the association between age and clinical outcomes. P values < 0.05 (two-sided) were considered statistically significant.
The mean age of the cohort was 58.8 ± 10.3 years. The percentages of patients < 65, 65–69, 70–74, and ≥ 75 years were 66.7 %, 19.3 %, 9.2 % and 4.8 %, respectively. Compared to the aged < 65 years group, the HR for the risk of disease progression for each group are 0.67 (95 %CI = 0.40–1.12, P = 0.125), 0.66 (95 %CI = 0.31, 1.43, P = 0.298), and 2.27 (95 %CI = 0.80, 6.45, P = 0.124), respectively, with no significant differences in the results. And the HR for risk of death for the 65–69 years and 70–74 years groups was 1.16 (95 %CI = 0.64–2.08, P = 0.628) and 0.93 (95 %CI = 0.39–2.23, P = 0.879), respectively. The difference has no statistical significance. Whereas in patients aged ≥ 75, there is an increased risk of death after adjusted confounders with HR = 4.83 (95 %CI = 2.06–11.35). The difference was statistically significant (P < 0.001). Trend test indicates that with advancing age, the patient's risk of death increases (HR = 1.33, 95 % CI = 1.02–1.75, P = 0.034).
Age may not be the primary factor influencing the efficacy of immunotherapy combined with chemotherapy, but particular attention should be given to the elderly population.
The Role of Thoracic Vertebral Body Dosimetry in Minimizing Acute Hematologic Toxicities of Patients With Non-Small Cell Lung Cancer Receiving Lung Radiation Therapy and Immunotherapy
2024, International Journal of Radiation Oncology Biology Physics
Hematologic toxicities (HTs) are among the most common toxicities of combined immunotherapy and radiation therapy (RT). It remains essential to prevent RT-induced HTs because they can cause treatment discontinuation (influencing antitumoral effects) and because lymphopenia might dampen the effects of immunotherapy. To date, there are no studies examining the effect of thoracic vertebral body (TVB) RT dose on HTs in patients with non-small cell lung cancer receiving combined lung RT and programmed cell death (ligand) 1 immunotherapy.
For standardization, all doses were reported as 2-Gy equivalents (EQD2). Mirroring publications before the immunotherapy era, TVB volumes referred to T1-T10, and specific dosimetric parameters (Dmean_EQD2, V5_EQD2-V60_EQD2) were analyzed. Logistic regression estimated associations between grade ≥3 HTs (HT3+) and dosimetric/clinical parameters. Normal tissue complication probability (NTCP) models were constructed by logistic regression analysis modeling for HT3+. Receiver operating characteristic (ROC) analysis delineated TVB dosimetric thresholds, the stratification of which was able to evaluate post-RT absolute lymphocyte count and immunotherapy responses. Areas under the curve (AUCs) for NTCP models were corroborated by bootstrapping (optimism-corrected) methodology.
In 132 patients, there were 26 (19.7%) instances of HT3+. On multivariate analysis, Dmean_EQD2 and V5_EQD2 to V20_EQD2 were associated with HT3+ (P < .05 for all). The NTCP models illustrated a 50% probability of HT3+ at a Dmean_EQD2 = 39.8 Gy, V5_EQD2 = 87.4%, V10_EQD2 = 77.0%, and V20_EQD2 = 68.4%. ROC analysis delineated optimal thresholds of HT3+ with Dmean_EQD2 ± 30.2 Gy, V5_EQD2 ± 69.1%, V10_EQD2 ± 64.6%, and V20_EQD2 ± 53.5%. Patients treated with values above those cutoffs had over double the risk of HT3+, with significant differences in post-RT absolute lymphocyte count and immunotherapy responses (P < .05 for all). AUCs for each individual parameter ranged from 0.743 to 0.798, and combining all 4 aforementioned cutoffs into a ROC curve resulted in a qualitatively higher AUC (0.836).
This hypothesis-generating work suggests that TVB dosimetry may equate with HT3+ in patients with non-small cell lung cancer undergoing combined lung RT/immunotherapy. Applying TVB dose constraints in this population could reduce HT3+ and avoid dampening of immunotherapy responses, but prospective validation is required.
Identification of nomogram associated with durable clinical benefit gene for advanced non-small cell lung cancer with sensitivity to responsive to immunotherapy
2024, Heliyon
Immunotherapy has become the standard treatment for advanced non-small cell lung cancer (NSCLC). However, a subset of the most advanced NSCLC patients fails to respond adequately to Immune checkpoint inhibitors (ICIs). Developing new nomograms and integrating prognostic factors are crucial for improving the clinical predictability of NSCLC patients undergoing ICIs.
Clinical information and genomic data of NSCLC patients undergoing ICIs were retrieved from cBioPortal. Gene alterations associated with durable clinical benefit (DCB) were compared to those linked to no durable benefit (NDB). The Kaplan-Meier plot method was employed for survival analysis, and a novel nomogram was formulated by selecting pertinent clinical variables.
For the NSCLC patients receiving immunotherapy, three subgroups were identified based on the treatment regimen, including anti-PD-1 monotherapy, anti-PD-1 combination with anti–CTLA–4, and first-line treatment. The mutation status of TP53, PGR, PTPRT, RELN, MUC19, LRP1B, and FAT3 was found to be associated with progression-free survival (PFS). Using the clinicopathological parameters and genomic data of the patients, we developed three novel nomograms to predict the prognosis of ICI treatment in different subgroups.
Our study revealed that PGR, PTPRD, RELN, MUC19, LRP1B, and FAT3 mutation could serve as predictive biomarkers. Our systematic nomograms demonstrate significant potential in predicting the prognosis for NSCLC patients with sensitivity to different ICI treatment strategies.
Checkpoint Inhibitor Monotherapy in Potentially Trial-Eligible or Trial-Ineligible Patients With Metastatic NSCLC in the German Prospective CRISP Registry Real-World Cohort (AIO-TRK-0315)
2024, JTO Clinical and Research Reports
Patients with metastatic NSCLC (mNSCLC) treated with immune checkpoint inhibitors in clinical practice may often not meet the strict inclusion criteria of clinical trials. Our aim was to assess the trial eligibility of patients with mNSCLC treated with pembrolizumab monotherapy in real-world and to compare the outcome of “trial-ineligible” and “potentially trial-eligible” patients.
Data from the prospective, clinical research platform CRISP were used to compare patient characteristics, treatment, and outcome of patients with programmed cell death-ligand 1 tumor proportion score greater than or equal to 50% tumors treated with pembrolizumab monotherapy who are deemed either “potentially trial-eligible” or “trial-ineligible” according to inclusion and exclusion criteria of the registrational studies (KEYNOTE-024 and -042).
Of 746 patients included, 343 patients (46.0%) were classified as “trial-ineligible” and had significantly worse outcomes compared with “potentially trial-eligible” patients (n = 403, 54.0%): median progression-free survival: 6.2 (95% confidence interval [CI]: 5.2–8.4) versus 10.3 (95% CI: 8.4–13.8) months, hazard ratio (trial-ineligible versus potentially trial-eligible) of 1.43 (95% CI: 1.19–1.72), p less than 0.001; median overall survival: 15.9 (95% CI: 11.4–20.3) versus 25.3 (95% CI: 19.8–30.4) months, hazard ratio of 1.36 (95% CI: 1.10–1.67), p equals 0.004.
Our data reveal that a considerable proportion of patients with mNSCLC are not eligible to participate in a clinical trial and were found to have worse outcomes than potentially trial-eligible patients, whose outcomes were comparable with those obtained from pivotal clinical trials. This is of substantial clinical relevance for physicians discussing outcomes to be expected with their patients and stresses the need for real-world effectiveness analyses.

View all citing articles on Scopus

^†: A complete list of investigators is provided in the appendix

View full text

ArticlesPembrolizumab 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

Summary

Background

Methods

Findings

Interpretation

Funding

Introduction

Section snippets

Study design and patients

Results

Discussion

Data sharing

Lancet Oncol

Lancet

Lancet

J Thorac Oncol

J Thorac Oncol

Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer

N Engl J Med

Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma

N Engl J Med

Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR

N Engl J Med

First-line crizotinib versus chemotherapy in ALK-positive lung cancer

N Engl J Med

Alectinib versus crizotinib in untreated ALK-positive non-small-cell lung cancer

N Engl J Med

Pembrolizumab for the treatment of non-small-cell lung cancer

N Engl J Med

Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer

N Engl J Med

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

J Clin Oncol

Articles
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