Efficacy and safety of pembrolizumab in patients with advanced mesothelioma in the open-label, single-arm, phase 2 KEYNOTE-158 study

Yap, Timothy A.; Nakagawa, Kazuhiko; Fujimoto, Nobukazu; Kuribayashi, Kozo; Guren, Tormod Kyrre; Calabrò, Luana; Shapira‐Frommer, Ronnie; Gao, Bo; Kao, Steven; Matos, Ignacio; Planchard, David; Chatterjee, Arkendu; Jin, Fan; Norwood, Kevin; Kindler, Hedy L.

doi:10.1016/s2213-2600(20)30515-4

Cited by 52 publications

(47 citation statements)

References 26 publications

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“…Another trial with pembrolizumab that included 26 patients with a performance status of WHO 0-1 and failure of previous treatment reported up to 18 months long overall survival. The overall response rate in these immunotherapy trials was around 20-30% [33]. However, when we consider potentially severe toxicities, such as pneumonitis, the results of these trials were far from miraculous [34].…”

Section: Immunotherapy In Mesothelioma Checkpoint Inhibitors and New ...mentioning

confidence: 99%

Novel and Future Treatment Options in Mesothelioma: A Systematic Review

Štrbac

Dolžan

2022

IJMS

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Mesothelioma is a rare tumor, frequently associated with asbestos exposure, arising from pleura and peritoneum. Traditionally, diagnosis and treatment have been difficult in a clinical setting. The treatment is based on a trimodal approach involving surgery, chemotherapy, and radiotherapy. The introduction of chemotherapy improved the overall survival. However, the regimen of pemetrexed/cisplatin doublet has not been changed as a standard treatment since 2004. Novel combinations of ipilimumab and nivolumab have only been approved for clinical use in late 2020. The aim of this review was to systematically summarize findings on novel treatment options in mesothelioma. We searched available medical databases online, such as PubMed and Clinicaltrials.gov, to systematically review the literature on novel approaches in immunotherapy, vaccines, and Chimeric Antigen Receptor (CAR)-T cell therapy in mesothelioma. We manually screened 1127 articles on PubMed and 450 trials on ClinicalTrials.gov, and 24 papers and 12 clinical trials published in the last ten years were included in this review. Immunotherapy that was swiftly introduced to treat other thoracic malignancies was slow to reach desirable survival endpoints in mesothelioma, possibly due to limited patient numbers. Novel treatment approaches, such as CAR-T cell therapy, are being investigated. As the incidence of mesothelioma is still rising globally, novel treatment options based on a better understanding of the tumor microenvironment and the genetic drivers that modulate it are needed to support future precision-based therapies.

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Section: Immunotherapy In Mesothelioma Checkpoint Inhibitors and New ...mentioning

confidence: 99%

Novel and Future Treatment Options in Mesothelioma: A Systematic Review

Štrbac

Dolžan

2022

IJMS

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“…In the phase 1b trial KEYNOTE-028, which evaluated pembrolizumab (an anti-PD-1 mAb) 10 mg/kg q14 in PD-L1-positive solid tumors, a cohort of 25 patients with MPM exhibited a median OS of 18 months and DCR of 72%, with 4 patients maintaining a response for about two years [ 21 ]. In the multicohort, single-arm, phase 2 KEYNOTE-158 study [ 22 ], 118 patients with pre-treated MPM and biomarker-evaluable tumor samples were enrolled to receive pembrolizumab 200 mg intravenously every 3 weeks for up to 35 cycles. The primary study endpoint was ORR, and only 10 patients (8%; 95% CI; 4–15) had an objective response; the median DOR was 14·3 months (range: 4.0 to over 33.9), and 60% of objective responses were ongoing at 12 months.…”

Section: Immunotherapymentioning

confidence: 99%

Oncological Frontiers in the Treatment of Malignant Pleural Mesothelioma

Vita

Stefani

Salvatore

et al. 2021

JCM

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Malignant pleural mesothelioma (MPM) is a rare malignancy characterized by very poor prognosis and lack of treatment options. Immunotherapy has rapidly emerged as an effective tool for MPM, particularly for tumors of non-epithelioid histology. At the same time, comprehensive genomic sequencing may open the way to new-generation targeted-drugs able to hit specific MPM molecular vulnerabilities. These innovations will possibly enrich, but also dramatically complicate, the elucidation of treatment algorithms. Multidisciplinary integration is urgently needed.

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“… 28 According to the Phase II trial KEYNOTE-158, pembrolizumab exhibited persistent anticancer effect and tolerable toxic effect on advanced MPM cases, despite the PD-L1 status. 29 In the NivoMes Phase II study, enrolling 38 patients with relapsed MPM was treated with nivolumab, obtaining a 3-month DCR (Disease control rate, DCR) of 50% and an ORR of 24%. 30 3-Year Results of the MERIT Study showed that receiving nivolumab intravenously 240 mg every 2 weeks was well tolerated and no new safety signals were found.…”

Section: Immunotherapymentioning

confidence: 99%

Advances in Immunotherapy of Malignant Pleural Mesothelioma

Liao¹,

Yu²,

Mei³

et al. 2021

OTT

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Malignant pleural mesothelioma (MPM) represents the uncommon cancer originating from pleural mesothelial cells, which is associated with dismal prognostic outcome. According to CheckMate-743 results, nivolumab plus ipilimumab has been approved to treat the unresectable MPM in treatment-naive patients as a first-line therapy by the FDA in October 2020. Immunotherapy is expected to be the best choice for MPM treatment. In the following article, the past treatment plan and the progress of immunotherapy for MPM will be reviewed.

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Efficacy and safety of pembrolizumab in patients with advanced mesothelioma in the open-label, single-arm, phase 2 KEYNOTE-158 study

Cited by 52 publications

References 26 publications

Novel and Future Treatment Options in Mesothelioma: A Systematic Review

Novel and Future Treatment Options in Mesothelioma: A Systematic Review

Oncological Frontiers in the Treatment of Malignant Pleural Mesothelioma

Advances in Immunotherapy of Malignant Pleural Mesothelioma

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