First-line nivolumab plus ipilimumab combined with two cycles of chemotherapy in patients with non-small-cell lung cancer (CheckMate 9LA): an international, randomised, open-label, phase 3 trial

Paz‐Ares, Luis; Ciuleanu, Tudor-Eliade; Cobo, Manuel; Schenker, Michael; Żurawski, Bogdan; Menezes, J.; Richardet, Eduardo; Bennouna, Jaafar; Felip, Enriqueta; Juan, Óscar; Alexandru, Aurelia; Sakai, Hiroshi; Lingua, Alejo; Salman, Pamela; Souquet, Pierre-Jean; Marchi, Pedro De; Martín, Claudio; Pérol, Maurice; Scherpereel, Arnaud; Lü, Shun; John, Thomas; Carbone, David P.; Meadows–Shropshire, S.; Agrawal, Shruti; Oukessou, Abderrahim; Yan, Jinchun; Reck, Martin

doi:10.1016/s1470-2045(20)30641-0

Cited by 836 publications

(574 citation statements)

References 22 publications

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“…However, researchers are still studying the effect of CTLA-4 inhibitors on NSCLC. According to the data published by the CheckMate 227 (ClinicalTrials.gov Identifier: NCT02477826) and CheckMate 9LA (ClinicalTrials.gov Identifier: NCT03215706) studies, which included KRAS-mutant NSCLC patients, first-line treatment with nivolumab plus ipilimumab led to better survival than did chemotherapy in patients with NSCLC, regardless of PD-L1 expression level (30,31).…”

Section: Progress In Immunotherapy Of Kras-mutant Nsclcmentioning

confidence: 99%

KRAS-Mutant Non-Small Cell Lung Cancer: An Emerging Promisingly Treatable Subgroup

Xie

Fan

2021

Front. Oncol.

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Lung cancer, the leading cause of cancer-related deaths worldwide, can be classified into small cell lung cancer and non-small cell lung cancer (NSCLC). NSCLC is the most common histological type, accounting for 85% of all lung cancers. Kirsten rat sarcoma viral oncogene (KRAS) mutations, common in NSCLC, are associated with poor prognosis, likely due to poor responses to most systemic therapies and lack of targeted drugs. The latest published clinical trial data on new small-molecule KRAS G12C inhibitors, AMG510 and MRTX849, indicate that these molecules may potentially help treat KRAS-mutant NSCLC. Simultaneously, within the immuno-therapeutic process, immune efficacy has been observed in those patients who have KRAS mutations. In this article, the pathogenesis, treatment status, progress of immunotherapy, and targeted therapy of KRAS-mutant NSCLC are reviewed.

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Section: Progress In Immunotherapy Of Kras-mutant Nsclcmentioning

confidence: 99%

KRAS-Mutant Non-Small Cell Lung Cancer: An Emerging Promisingly Treatable Subgroup

Xie

Fan

2021

Front. Oncol.

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“…LD chemotherapy could be omitted if the white blood cell count was <1000 cells/μL.” Whereas for axicabtagene ciloleucel, the product monograph states that “Bridging chemotherapy between leukapheresis and lymphodepleting chemotherapy was not permitted”. Furthermore, it should be mentioned that a number of chemo-immunotherapy regimens are now US FDA-approved as standard first-line treatment for patients with locally advanced or metastatic lung cancer [ 10 , 11 , 12 , 13 ]. The doublet cytotoxic chemotherapy, which is employed with an immune checkpoint inhibitor in these chemo-immunotherapy regimens, comprises a platinum drug and one of several different cytotoxic drugs, which may include pemetrexed, paclitaxel, vinorelbine, etoposide or gemcitabine.…”

Section: Introductionmentioning

confidence: 99%

Effects of Chemotherapy Agents on Circulating Leukocyte Populations: Potential Implications for the Success of CAR-T Cell Therapies

Truong

Gargett

Brown

et al. 2021

Cancers

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Adoptive T-cell therapy using autologous T cells genetically modified to express cancer-specific chimeric antigen receptors (CAR) has emerged as a novel approach for cancer treatment. CAR-T cell therapy has been approved in several major jurisdictions for treating refractory or relapsed cases of B-cell precursor acute lymphoblastic leukaemia and diffuse large B-cell lymphoma. However, in solid cancer patients, several clinical studies of CAR-T cell therapy have demonstrated minimal therapeutic effects, thus encouraging interest in better integrating CAR-T cells with other treatments such as conventional cytotoxic chemotherapy. Increasing evidence shows that not only do chemotherapy drugs have tumoricidal effects, but also significantly modulate the immune system. Here, we discuss immunomodulatory effects of chemotherapy drugs on circulating leukocyte populations, including their ability to enhance cytotoxic effects and preserve the frequency of CD8+ T cells and to deplete immunosuppressive populations including regulatory T cells and myeloid-derived suppressor cells. By modulating the abundance and phenotype of leukocytes in the blood (the ‘raw material’ for CAR-T cell manufacturing), we propose that prior chemotherapy could facilitate production of the most effective CAR-T cell products. Further research is required to directly test this concept and identify strategies for the optimal integration of CAR-T cell therapies with cytotoxic chemotherapy for solid cancers.

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“…Platinum-based chemotherapies may synergize with ICB, with single arm studies showing that combination chemo-immunotherapy reduces tumor burden and shows promising progression-free and overall survival outcomes for mesothelioma (17)(18)(19). In addition, complete tumor regression has been observed in some NSCLC (20)(21)(22) and SCLC (23)(24)(25) patients treated with chemo-immunotherapy. Atezolizumab and durvalumab are also approved in combination with platinum-based chemotherapy for advanced SCLC patients (26).…”

Section: There Is An Urgent Need To Develop Biomarkers Of Response To Immune Checkpoint Blockadementioning

confidence: 99%

Malignant Pleural Effusions—A Window Into Local Anti-Tumor T Cell Immunity?

Principe¹,

Kidman²,

Lake³

et al. 2021

Front. Oncol.

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The success of immunotherapy that targets inhibitory T cell receptors for the treatment of multiple cancers has seen the anti-tumor immune response re-emerge as a promising biomarker of response to therapy. Longitudinal characterization of T cells in the tumor microenvironment (TME) helps us understand how to promote effective anti-tumor immunity. However, serial analyses at the tumor site are rarely feasible in clinical practice. Malignant pleural effusions (MPE) associated with thoracic cancers are an abnormal accumulation of fluid in the pleural space that is routinely drained for patient symptom control. This fluid contains tumor cells and immune cells, including lymphocytes, macrophages and dendritic cells, providing a window into the local tumor microenvironment. Recurrent MPE is common, and provides an opportunity for longitudinal analysis of the tumor site in a clinical setting. Here, we review the phenotype of MPE-derived T cells, comparing them to tumor and blood T cells. We discuss the benefits and limitations of their use as potential dynamic biomarkers of response to therapy.

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First-line nivolumab plus ipilimumab combined with two cycles of chemotherapy in patients with non-small-cell lung cancer (CheckMate 9LA): an international, randomised, open-label, phase 3 trial

Cited by 836 publications

References 22 publications

KRAS-Mutant Non-Small Cell Lung Cancer: An Emerging Promisingly Treatable Subgroup

KRAS-Mutant Non-Small Cell Lung Cancer: An Emerging Promisingly Treatable Subgroup

Effects of Chemotherapy Agents on Circulating Leukocyte Populations: Potential Implications for the Success of CAR-T Cell Therapies

Malignant Pleural Effusions—A Window Into Local Anti-Tumor T Cell Immunity?

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