Carboplatin and pemetrexed with or without pembrolizumab for advanced, non-squamous non-small-cell lung cancer: a randomised, phase 2 cohort of the open-label KEYNOTE-021 study

Langer, Corey J.; Gadgeel, Shirish M.; Borghaei, Hossein; Papadimitrakopoulou, Vassiliki A.; Patnaik, Amita; Powell, Steven; Gentzler, Ryan D.; Martins, Renato; Stevenson, James P.; Jalal, Shadia I.; Panwalkar, Amit; Yang, James Chih‐Hsin; Gubens, Matthew A.; Sequist, Lecia V.; Awad, Mark M.; Fiore, Joseph; Ge, Yang; Raftopoulos, Harry; Gandhi, Leena

doi:10.1016/s1470-2045(16)30498-3

Cited by 1,238 publications

(1,135 citation statements)

References 29 publications

(32 reference statements)

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“…Combination therapy with another immunotherapeutic agent shows even greater promise, as seen when the addition of another checkpoint inhibitor antibody, nivolumab, a monoclonal antibody (mAb) which targets the PD-1 receptor on T-cells, produced a 50% response rate in metastatic melanoma [4,5] . CI has also shown effectiveness in other types of malignances, and combinations with different treatment modalities ("immuno-oncology") are also showing remarkable benefits [6,7] .…”

Section: Introductionmentioning

confidence: 99%

Cancer immunotherapy: a brief review of the history, possibilities, and challenges ahead

Oiseth¹,

Aziz²

2017

JCMT

260

199

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The knowledge that the body possesses natural defenses to combat cancer existed long before the modern period, with multiple anecdotal reports of tumors miraculously disappearing, sometimes spontaneously or after a febrile or infectious episode. Spontaneous tumor regression of untreated malignant tumors is currently a well-accepted albeit rare phenomenon, and it is recognized that immunosuppression is associated with a higher cancer risk. The treatment of bladder carcinoma by intravesical administration of live attenuated Bacillus CalmetteGuérin bacteria was shown to be very effective in 1976 and is now standard treatment. Effective immunity against cancer involves complex interactions between the tumor, the host, and the environment. Cancer immunotherapy uses various strategies to augment tumor immunity and represents a paradigm shift in treating cancer, since attention has become more focused on the "biologic passport" of the individual tumor rather than the site of origin of the tumor. The different types of cancer immunotherapies discussed here include biologic modifiers, such as cytokines and vaccines, adoptive cell therapies, oncolytic viruses, and antibodies against immune checkpoint inhibitors, such as the co-inhibitory T-cell receptor PD-1 and one of its ligands, programmed death-ligand 1. Key words:Cancer immunotherapy, immune checkpoint inhibitors, PD-1, programmed death-ligand 1, cytotoxic T-lymphocyte-associated antigen-4, adoptive cell therapy, cancer vaccines, oncolytic viruses, history of cancer immunology ABSTRACTArticle history:

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Section: Introductionmentioning

confidence: 99%

Cancer immunotherapy: a brief review of the history, possibilities, and challenges ahead

Oiseth¹,

Aziz²

2017

JCMT

260

199

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“…The initial approval of ipilimumab/nivolumab combination therapy for first-line treatment of melanoma was based on the high ORR reported with this combination versus single-agent ipilimumab in the CheckMate 069 study (Table 3) [35], and was further supported by the phase 3 CheckMate 067 study, which showed significant improvements in median PFS [12,24]. The accelerated approval of pembrolizumab plus chemotherapy (pemetrexed/carboplatin) for first-line treatment of non-squamous NSCLC was based on the high ORR reported with this combination versus pemetrexed/carboplatin alone in the KEYNOTE-021 trial (Table 3) [52]. Additional immunotherapy-based combination therapies are being tested in phase 3 studies (Table 4), and for some of these combination approaches, preliminary data are available ( Table 3).…”

Section: Immunotherapy-based Combination Approachesmentioning

confidence: 96%

“…Several ICBs have gained FDA accelerated approval based on ORR, including atezolizumab, nivolumab, durvalumab, and avelumab in previously treated patients with UC [12,[14][15][16]; pembrolizumab in previously treated patients with HNSCC [13]; combination nivolumab plus ipilimumab in melanoma [80]; and pembrolizumab in NSCLC, as monotherapy or in combination with chemotherapy [13,41,52]. PFS has been investigated in several meta-analyses as a surrogate endpoint for OS in metastatic melanoma [75,81], and has served as the basis for FDA approval of first-line pembrolizumab in patients with NSCLC [13].…”

Section: Endpoints To Assess Clinical Outcomes Associated With Icbsmentioning

confidence: 99%

Immune Checkpoint Blockade: The New Frontier in Cancer Treatment

et al. 2018

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Immune checkpoint blockers have revolutionized cancer treatment in recent years. These agents are now approved for the treatment of several malignancies, including melanoma, squamous and non-squamous non-small cell lung cancer, renal cell carcinoma, urothelial carcinoma, and head and neck squamous cell carcinoma. Studies have demonstrated the significant impact of immunotherapy versus standard of care on patient outcomes, including durable response and extended survival. The use of immunotherapy-based combination therapy has been shown to further extend duration of response and survival. Immunotherapies function through modulation of the immune system, which can lead to immune-mediated adverse events (imAEs). These include a range of dermatologic, gastrointestinal, endocrine, and hepatic toxicities, as well as other less common inflammatory events. ImAEs are typically low grade and manageable when identified early and treated with appropriate measures. Identifying the right patient for the right therapy will become more important as new immunotherapies and immunotherapy-based combinations are approved and costs of cancer care continue to rise.

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“…Immunotherapy can also be efficacious in solid tumors with high somatic mutational burden, including NSCLC (18)(19)(20). The most promising examples include multiple anti-programmed cell death protein 1 (PD-1)/antiprogrammed death-ligand 1 (PD-L1) immune checkpoint inhibitors.…”

Section: Introductionmentioning

confidence: 99%

Moving more potent and less toxic options to the frontline in the management of advanced lung cancer

Rangachari

Costa

2017

J. Thorac. Dis.

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Carboplatin and pemetrexed with or without pembrolizumab for advanced, non-squamous non-small-cell lung cancer: a randomised, phase 2 cohort of the open-label KEYNOTE-021 study

Abstract: Merck & Co.

Cited by 1,238 publications

References 29 publications

Cancer immunotherapy: a brief review of the history, possibilities, and challenges ahead

Cancer immunotherapy: a brief review of the history, possibilities, and challenges ahead

Immune Checkpoint Blockade: The New Frontier in Cancer Treatment

Moving more potent and less toxic options to the frontline in the management of advanced lung cancer

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