Atezolizumab in patients with advanced non-small cell lung cancer and history of asymptomatic, treated brain metastases: Exploratory analyses of the phase III OAK study

Gadgeel, Shirish M.; Lukas, Rimas V.; Goldschmidt, Jerome H.; Conkling, Paul; Park, Keunchil; Cortinovis, Diego; Marinis, Filippo de; Rittmeyer, Achim; Patel, Jyoti D.; Pawel, Joachim von; O’Hear, Carol; Lai, Catherine; Hu, Sylvia; Ballinger, Marcus; Sandler, Alan; Gandhi, M.; Fehrenbacher, L.

doi:10.1016/j.lungcan.2018.12.017

Cited by 142 publications

(97 citation statements)

References 20 publications

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“…To our knowledge, this is the first study to focus on the population of patients with brain metastases from lung cancer and examine the effects of immunotherapy. Other studies have demonstrated that patients with brain metastases from NSCLC can benefit from immunotherapy both as a single agent 5,19,20 and in combination with chemotherapy, 21 however these reports were based on subset analyses from larger trials and did not assess the specific characteristics of the CNS disease. Several expanded access programs and observational studies examining patients with NSCLC treated with singleagent PD-1 or PD-L1 inhibitors found that clinical outcomes (including efficacy and safety) were similar in patients with versus without brain metastases, highlighting that both PD-1 and PD-L1 inhibitors can be effective in patients with CNS disease.…”

Section: Discussionmentioning

confidence: 99%

Pembrolizumab for management of patients with NSCLC and brain metastases: long-term results and biomarker analysis from a non-randomised, open-label, phase 2 trial

Goldberg

Schalper

Gettinger

et al. 2020

The Lancet Oncology

410

319

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Background: We performed a phase II trial of pembrolizumab in patients with NSCLC or melanoma with untreated brain metastases to determine the activity of PD-1 blockade in the CNS. Interim results were previously published, and we now report an updated analysis of the full NSCLC cohort. Methods: This was an open-label, single-institution, phase 2 study. Eligible patients were ≥ 18 years of age with advanced NSCLC with ≥1 brain metastasis 5-20mm not previously treated or progressing after prior radiation, no neurologic symptoms or corticosteroid requirement, and performance status <2. Patients were treated with pembrolizumab 10 mg/kg IV every 2 weeks. Cohort 1 was for patients with PD-L1 ≥1% and cohort 2 PD-L1 <1% or unevaluable. The primary endpoint was the proportion of patients achieving a brain metastasis response. All treated patients were analyzed for response and safety endpoints. This study is closed to accrual and is registered with Clinicaltrials.gov, number NCT02085070. Here we report the updated results of the NSCLC cohort. Findings: Between March 31, 2014 and May 21, 2018, 42 patients were treated. Median followup was 8.3 months (IQR 4.5 to 26.2 months). Eleven of 37 patients in cohort 1 had a brain metastasis response (29.7% [95% CI, 15•9-47•0%]). There were no responses in cohort 2. Grade 3-4 AEs related to treatment included 2 patients with pneumonitis, and 1 each with constitutional symptoms, colitis, adrenal insufficiency, hyperglycemia, and hypokalemia. Treatment-related serious adverse events occurred in 6 (14%) patients and included pneumonitis acute kidney injury, colitis, hypokalemia, and adrenal insufficiency. There were no treatment-related deaths. Interpretation: Pembrolizumab has activity in brain metastases from NSCLC with PD-L1 expression ≥1% and is safe in select patients with untreated brain metastases. Further investigation of immunotherapy in patients with CNS disease from NSCLC is warranted.

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Section: Discussionmentioning

confidence: 99%

Pembrolizumab for management of patients with NSCLC and brain metastases: long-term results and biomarker analysis from a non-randomised, open-label, phase 2 trial

Goldberg

Schalper

Gettinger

et al. 2020

The Lancet Oncology

410

319

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“…A total of 1,232 studies was initially identified, 163 of which were excluded due to duplications. After screening abstract and full text of references according to the eligible criteria, eight studies were included (15,(21)(22)(23)(24)(25)(26)(27). Figure 1 shows the process of study selection.…”

Section: Eligible Studies and Characteristicsmentioning

confidence: 99%

Efficacy of Immune Checkpoint Inhibitors in Non-small-cell Lung Cancer Patients With Different Metastatic Sites: A Systematic Review and Meta-Analysis

Yang

Bai

et al. 2020

Front. Oncol.

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Background: Organ-specific response patterns reported in previous studies indicate different response toward immune checkpoint inhibitors (ICIs) in non-small-cell lung cancer (NSCLC) patients with different metastatic sites. This study aims to compare the efficacy of ICIs with conventional therapy in NSCLC patients with bone, brain or liver metastases. Materials and Methods: MEDLINE, Embase, and CENTRAL were searched for studies comparing ICIs with conventional therapy in NSCLC patients with bone, brain or liver metastases. The pooled hazard ratio (HR) of overall survival (OS) and progression-free survival (PFS) among included studies was analyzed using the random effects model. Results: Eight studies consisting of 988 NSCLC patients were included, 259 with brain metastases and 729 with liver metastases. No available study with bone metastases information was identified. For patients with brain metastases, ICIs significantly improved their OS (HR, 0.57; P = 0.007). For patients with liver metastases, both OS (HR, 0.72; P = 0.006), and PFS (HR, 0.72; P = 0.004) improvements were observed in the ICI treatment arm. Subgroup analysis was conducted based on target of ICIs and treatment regimen. PD-1 inhibitors could benefit patients with liver or brain metastases on OS and PFS (brain metastases: OS, HR, 0.43; P < 0.001; liver metastases: PFS, HR, 0.52; P = 0.003; OS, HR, 0.66; P = 0.001), while PD-L1 inhibitors could not. Patients with brain metastases could only gain OS improvement from ICIs combined with chemotherapy (HR, 0.41; P = 0.001), but for patients with liver metastases, the benefit was detected using ICIs single agent (HR, 0.68; P = 0.012) or ICIs combined with chemotherapy plus anti-VEGF therapy (HR, 0.52; P = 0.005). Conclusion: ICIs could significantly improve OS in NSCLC patients with brain or liver metastases compared with conventional therapy. Patients with brain metastases could only gain OS benefit from ICIs combined with chemotherapy, while those with liver metastases obtained superior OS from ICIs single agent or ICIs combined with chemotherapy plus anti-VEGF therapy.

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“…The other studies were not clearly stated. These studies were mainly based on the following clinical trials: KEYNOTE 024, 13 KEYNOTE 042, 10 KEYNOTE 189, 14 KEYNOTE 407, 15 KEYNOTE 010 5 , CheckMate 057, 16 CheckMate 017, 17 CheckMate 078, 18 the OAK trial, 19 and IMpower150. 20 The basic characteristics and results of the studies are shown in Tables 1 and 2, respectively.…”

Section: General Characteristicsmentioning

confidence: 99%

<p>Economic Evaluations of Immune Checkpoint Inhibitors for Patients with Non-Small Cell Lung Cancer: A Systematic Review</p>

Zheng

et al. 2020

CMAR

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This review aimed to assess the quality of available evidence on the economic evaluations of immune checkpoint inhibitors in patients with non-small cell lung cancer (NSCLC) and provide evidence to improve the efficiency of healthcare resources. Materials and Methods: Literature search was performed using some electronic databases (PubMed, Embase and Cochrane Central Register of Controlled Trials). Final search was performed in December 2019. Study characteristics and results were recorded and compared. The quality of the studies was assessed using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklists. We did not elaborate the restrictions on the target population. We included patients with squamous or non-squamous NSCLC and metastatic or advanced cancer. Results: Of 98 papers considered, 21 were chosen for this review. Most of them are costeffectiveness analysis. Comparative regimens consisted of either immune checkpoint inhibitor monotherapy, immune checkpoint inhibitor plus chemotherapy, or chemotherapy alone. Fourteen, four, and three studies were about pembrolizumab, nivolumab, and atezolizumab, respectively. The methods mostly used in these studies were modeling and sensitivity analysis. All studies used quality-adjusted life year (QALY) and life years (LY) as outcomes. Most studies were conducted in high-income countries. Based on the willingness to pay threshold, atezolizumab, and pembrolizumab were found to be cost-effective in one and 10 studies, respectively. None of the studies concluded that nivolumab was cost-effective. For quality assessment, all studies fulfilled more than 50% of the CHEERS checklist. Conclusion: The included studies indicated that pembrolizumab regimens are cost-effective as first-line treatment for patients with NSCLC in developed countries. Nivolumab and atezolizumab are likely to be cost-effective as second-line treatment but not as first-line treatment.

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Atezolizumab in patients with advanced non-small cell lung cancer and history of asymptomatic, treated brain metastases: Exploratory analyses of the phase III OAK study

Cited by 142 publications

References 20 publications

Pembrolizumab for management of patients with NSCLC and brain metastases: long-term results and biomarker analysis from a non-randomised, open-label, phase 2 trial

Pembrolizumab for management of patients with NSCLC and brain metastases: long-term results and biomarker analysis from a non-randomised, open-label, phase 2 trial

Efficacy of Immune Checkpoint Inhibitors in Non-small-cell Lung Cancer Patients With Different Metastatic Sites: A Systematic Review and Meta-Analysis

<p>Economic Evaluations of Immune Checkpoint Inhibitors for Patients with Non-Small Cell Lung Cancer: A Systematic Review</p>

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