Randomized Feasibility Study of De-escalated (Every 12 wk) Versus Standard (Every 3 to 4 wk) Intravenous Pamidronate in Women With Low-risk Bone Metastases From Breast Cancer

Amir, Eitan; Freedman, Orit; Carlsson, Lindsay; Dranitsaris, George; Tomlinson, George; Laupacis, Andreas; Tannock, Ian F.; Clemons, Mark

doi:10.1097/coc.0b013e3182568f7a

Cited by 34 publications

(67 citation statements)

References 9 publications

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“…21 Interestingly, we observed the monotherapeutic αCTLA-4 immune checkpoint administration resulted in clusters of PD-1 + T-cells (Fig. 3A), supporting recent observations that immune checkpoint blocking antibodies preferentially expand exhausted phenotype T-cells in both mice and man.…”

Section: Resultssupporting

confidence: 88%

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Combination of dual mTORC1/2 inhibition and immune-checkpoint blockade potentiates anti-tumour immunity

et al. 2018

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ABSTRACTmTOR inhibition can promote or inhibit immune responses in a context dependent manner, but whether this will represent a net benefit or be contraindicated in the context of immunooncology therapies is less understood. Here, we report that the mTORC1/2 dual kinase inhibitor vistusertib (AZD2014) potentiates anti-tumour immunity in combination with anti-CTLA-4 (αCTLA-4), αPD-1 or αPD-L1 immune checkpoint blockade. Combination of vistusertib and immune checkpoint blocking antibodies led to tumour growth inhibition and improved survival of MC-38 or CT-26 pre-clinical syngeneic tumour models, whereas monotherapies were less effective. Underlying these combinatorial effects, vistusertib/immune checkpoint combinations reduced the occurrence of exhausted phenotype tumour infiltrating lymphocytes (TILs), whilst increasing frequencies of activated Th1 polarized T-cells in tumours. Vistusertib alone was shown to promote a Th1 polarizing proinflammatory cytokine profile by innate primary immune cells. Moreover, vistusertib directly enhanced activation of effector T-cell and survival, an effect that was critically dependent on inhibitor dose. Therefore, these data highlight direct, tumour-relevant immune potentiating benefits of mTOR inhibition that complement immune checkpoint blockade. Together, these data provide a clear rationale to investigate such combinations in the clinic.

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Section: Resultssupporting

confidence: 88%

“…Downstream analysis was performed using FlowJo software (V10) and viSNE (Cytobank) high-dimensional, single-cell analysis. 21 …”

Section: Methodsmentioning

confidence: 99%

Combination of dual mTORC1/2 inhibition and immune-checkpoint blockade potentiates anti-tumour immunity

et al. 2018

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“…For example, our group has an interest in de-escalation of bone-targeted therapies for patients with metastatic bone disease. We staggered our work into short-term projects (commentaries 9 , editorials, pilot chart review 10 , review articles), medium-term projects (surveys of patients and physicians to demonstrate clinical equipoise 11 , systematic reviews 12 ), and longer-term projects (creation of pilot singlearm and randomized feasibility data studies 13,14 ). Deadlines are thus spread out and the payoffs are layered-all hopefully one day leading to funding for a larger phase iii trial.…”

Section: Be Smart With Your Timementioning

confidence: 99%

Publishing Clinical Research: Ten Pearls for Oncology Trainees and Junior Oncologists

et al. 2015

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on to other rotations), energy is sapped. By the time the project finishes, the researcher is disappointed and frustrated. Common examples are case reports and retrospective chart reviews-projects that are commonly pursued by junior trainees and junior faculty. Although such projects can require little planning and relatively less time than must be devoted to larger undertakings, I (MC) find that they often require a disproportionate amount of time and energy relative to their research merit. Unless a case report is truly novel, it should generally be avoided. Chart reviews also take longer than anticipated and are limited by a relatively small sample size. Like case reports, they are not often published in high-quality journals. There are two scenarios in which such projects can be fruitful pursuits. First, when the data are already collected, available electronically, and easy to abstract. Second, when a small sample is collected for the purpose of piloting a larger and more formal study. If the data are of sufficient interest, the results can be used to establish collaborative research with a larger group that might have their own prospectively collected data. Those more robust data can then be used as part of grant submissions and, hopefully, a prospective study.Acting as senior investigator on a randomized phase iii trial might be considered an ultimate way of having research affect patient care, but we are living in a time of increasing fiscal constraint, and with the amalgamation of collaborative groups, the opportunities for leadership roles will likely decrease 7 .

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“…Both trials reported a noninferiority of the 12-week schedule in this low-risk group. 73,74 Two other studies tested the reduction of therapy frequency from every 4 weeks to every 12 weeks after a treatment period of B1 year with ZA every 4 weeks. 75,76 Both studies reported a noninferiority of an every 12-week therapy schedule after at least 1 year of every 4-week ZA in terms of SREs; however, a significant increase in NTX-I levels from baseline in the every 12-week group was found.…”

Section: Dosing Of Btasmentioning

confidence: 99%

Bone remodeling markers and bone metastases: From cancer research to clinical implications

Ferreira¹,

Alho²,

Casimiro³

et al. 2015

BoneKEy Reports

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Bone metastasis is a frequent finding in the natural history of several types of cancers. However, its anticipated risk, diagnosis and response to therapy are still challenging to assess in clinical practice. Markers of bone metabolism are biochemical by-products that provide insight into the tumor-bone interaction, with potential to enhance the clinical management of patients with bone metastases. In fact, these markers had a cornerstone role in the development of bone-targeted agents; however, its translation to routine practice is still unclear, as reflected by current international guidelines. In this review, we aimed to capture several of the research and clinical translational challenges regarding the use of bone metabolism markers that we consider relevant for future research in bone metastasis.

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Randomized Feasibility Study of De-escalated (Every 12 wk) Versus Standard (Every 3 to 4 wk) Intravenous Pamidronate in Women With Low-risk Bone Metastases From Breast Cancer

Cited by 34 publications

References 9 publications

Combination of dual mTORC1/2 inhibition and immune-checkpoint blockade potentiates anti-tumour immunity

Combination of dual mTORC1/2 inhibition and immune-checkpoint blockade potentiates anti-tumour immunity

Publishing Clinical Research: Ten Pearls for Oncology Trainees and Junior Oncologists

Bone remodeling markers and bone metastases: From cancer research to clinical implications

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