Pembrolizumab (MK-3475) in patients (pts) with extensive-stage small cell lung cancer (SCLC): Preliminary safety and efficacy results from KEYNOTE-028.

Ott, Patrick A.; Fernandez, M.E. Elez; Hiret, Sandrine; Kim, Dong-Wan; Moss, Rebecca A.; Winser, Tammy; Yuan, Sammy; Cheng, Jonathan D.; Piperdi, Bilal; Mehnert, Janice M.

doi:10.1200/jco.2015.33.15_suppl.7502

Cited by 74 publications

(44 citation statements)

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“…Overall response was reported in 7/40 pts (18%) with nivolumab alone and in 8/46 pts (17%) in the combination therapy 152 . In the phase IB KEYNOTE-028 study SCLC patients with PD-L1 positive tumor who failed or were ineligible for standard therapy were treated with pembrolizumab (humanized monoclonal IgG4 PD-1 inhibitor antibody); the overall response was reported to be 35% and safety profile consistent with other PDL-1 studies 153 . Another two studies are exploring the efficacy of combination of pembrolizumab with chemotherapy/radiotherapy for extensive SCLC (NCT02359019, NCT02402920).…”

Section: Sclc Immunotherapymentioning

confidence: 84%

Small Cell Lung Cancer: Can Recent Advances in Biology and Molecular Biology Be Translated into Improved Outcomes?

Bunn

Minna

Augustyn

et al. 2016

Journal of Thoracic Oncology

154

123

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Section: Sclc Immunotherapymentioning

confidence: 84%

Small Cell Lung Cancer: Can Recent Advances in Biology and Molecular Biology Be Translated into Improved Outcomes?

Bunn

Minna

Augustyn

et al. 2016

Journal of Thoracic Oncology

154

123

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“…In light of these correlations, it is tempting to speculate that SCLC patients would exhibit good responses to ICI therapy. However, initial reports suggest that success rates to anti-PD1 therapy in SCLC are at best only comparable to NSCLC (58, 59). Our preliminary findings with respect to the immune cell composition in SCLC suggest that the presence of redundant immune suppressive factors would not be a likely source of treatment failure, which is almost certainly an important concept in NSCLC.…”

Section: Discussionmentioning

confidence: 99%

Lung Cancer Subtypes Generate Unique Immune Responses

Busch

Hanke

Kargl

et al. 2016

The Journal of Immunology

127

118

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Lung cancer – the leading cause of cancer-related deaths worldwide – is a heterogeneous disease comprised of multiple histologic subtypes that harbor disparate mutational profiles. Immune-based therapies have shown initial promise in the treatment of lung cancer patients but are currently limited by low overall response rates. We sought to determine whether the host immune response to lung cancer is predicated, at least in part, by histologic and genetic differences, as such correlations would have important clinical ramifications. Using mouse models of lung cancer, we show that small cell lung cancer (SCLC) and lung adenocarcinoma (ADCA) exhibit unique immune cell composition of the tumor microenvironment. The total amount of leukocyte content was markedly reduced in SCLC compared to lung ADCA, which was validated in human lung cancer specimens. We further identified key differences in immune cell content using three models of lung ADCA driven by mutations in Kras, Tp53, and Egfr. Although Egfr-mutant cancers displayed robust myeloid cell recruitment, they failed to mount a CD8+ immune response. In contrast, Kras-mutant tumors displayed significant expansion of multiple immune cell types, including CD8+ cells, regulatory T cells, IL17A-producing lymphocytes, and myeloid cells. A human tissue microarray annotated for KRAS and EGFR mutations validated the finding of reduced CD8+ content in human lung adenocarcinoma. Taken together, these findings establish a strong foundational knowledge of the immune cell contexture of lung ADCA and SCLC and suggest that molecular and histological traits shape the host immune response to cancer.

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“…In the SCLC cohort, 7 of 42 patients with progressive disease after platinum-based chemotherapy demonstrated a partial response to the PD-1 inhibitor pembrolizumab (ORR, 35%). 31 Six of these responses were ongoing at the time of data cutoff, suggesting durability. CheckMate 032 is a phase I/II trial investigating nivolumab with or without ipilimumab in PD-L1-unselected ES-SCLC patients with disease progression after standard first-line therapy.…”

Section: Small Cell Lung Cancermentioning

confidence: 97%

Immunotherapy for Advanced Lung Cancer

Asmar¹,

Rizvi²

2015

The Cancer Journal

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Lung cancers are immunogenic tumors that manage to evade the immune system by exploiting checkpoint pathways that render effector T cells anergic. Inhibition of these checkpoints can restore and invigorate endogenous antitumor T-cell responses. The immunotherapeutic approach of checkpoint inhibition has become an important treatment option for patients with advanced non-small cell lung cancer, playing a role that will continue to evolve over the coming years. The programmed death 1 inhibitors nivolumab and pembrolizumab have both been shown to induce durable responses and improve survival in a subset of patients with platinum-refractory metastatic non-small cell lung cancer. Nivolumab has recently earned Food and Drug Administration approval for progressive squamous cell lung cancer. Optimization and validation of a pretreatment biomarker to predict response is a key area of ongoing research. Combination therapy is now being investigated in an effort to improve response rates.

show abstract

Pembrolizumab (MK-3475) in patients (pts) with extensive-stage small cell lung cancer (SCLC): Preliminary safety and efficacy results from KEYNOTE-028.

Cited by 74 publications

References 0 publications

Small Cell Lung Cancer: Can Recent Advances in Biology and Molecular Biology Be Translated into Improved Outcomes?

Small Cell Lung Cancer: Can Recent Advances in Biology and Molecular Biology Be Translated into Improved Outcomes?

Lung Cancer Subtypes Generate Unique Immune Responses

Immunotherapy for Advanced Lung Cancer

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