Current Experience With CTLA4-blocking Monoclonal Antibodies for the Treatment of Solid Tumors

Agarwala, Sanjiv S.; Ribas, Antoni

doi:10.1097/cji.0b013e3181dcd260

Cited by 32 publications

(24 citation statements)

References 93 publications

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“…It has also been reported that the onset of IRAEs is associated with better clinical outcomes of underlying malignancy (73). However, whether the onset of hypophysitis in patients under anti-CTLA4-mAbs (or a specific grade of this toxicity) may predict better survival and/or response remains to be estimated in further trials with appropriate analytical approach (73).…”

Section: Discussionmentioning

confidence: 99%

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ENDOCRINE SIDE-EFFECTS OF ANTI-CANCER DRUGS: mAbs and pituitary dysfunction: clinical evidence and pathogenic hypotheses

Torino

Barnabei

Paragliola

et al. 2013

European Journal of Endocrinology

108

103

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mAbs are established targeted therapies for several diseases, including hematological and solid malignancies. These agents have shown a favorable toxicity profile, but, despite their high selectivity, new typical side-effects have emerged. In cancer patients, pituitary dysfunction may be mainly due to brain metastases or primary tumors and to related surgery and radiotherapy. Anticancer agents may induce hypopituitarism in patients cured for childhood cancers. These agents infrequently affect pituitary function in adult cancer patients. Notably, hypophysitis, a previously very rare disease, has emerged as a distinctive side-effect of ipilimumab and tremelimumab, two mAbs inhibiting the cytotoxic T-lymphocyte antigen-4 receptor, being occasionally seen with nivolumab, another immune checkpoint inhibitor. Enhanced antitumor immunity is the suggested mechanism of action of these drugs and autoimmunity the presumptive mechanism of their toxicity. Recently, ipilimumab has been licensed for the treatment of patients affected by metastatic melanoma. With the expanding use of these drugs, hypophysitis will be progressively encountered by oncologists and endocrinologists in clinical practice. The optimal management of this potentially life-threatening adverse event needs a rapid and timely diagnostic and therapeutic intervention. Hypopituitarism caused by these agents is rarely reversible, requiring prolonged or lifelong substitutive hormonal treatment. Further studies are needed to clarify several clinical and pathogenic aspects of this new form of secondary pituitary dysfunction.European Journal of Endocrinology 169 R153-R164

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Section: Discussionmentioning

confidence: 99%

“…However, whether the onset of hypophysitis in patients under anti-CTLA4-mAbs (or a specific grade of this toxicity) may predict better survival and/or response remains to be estimated in further trials with appropriate analytical approach (73).…”

Section: Discussionmentioning

confidence: 99%

ENDOCRINE SIDE-EFFECTS OF ANTI-CANCER DRUGS: mAbs and pituitary dysfunction: clinical evidence and pathogenic hypotheses

Torino

Barnabei

Paragliola

et al. 2013

European Journal of Endocrinology

108

103

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“…89Y91 In preclinical models, these strategies have been shown to enhance the vaccine-like effect of both chemotherapeutic and radiotherapeutic regimens, thereby constituting promising approaches. 91,79 Gulley and colleagues 92 reported that, in prostate cancer patients, the combination of radiotherapy with an admixture of a recombinant vaccine against prostatespecific antigen (PSA) and B7.1 costimulatory molecules induced a significant increase in PSA-specific and MUC1-specific T cells. The expansion of MUC1-specific T cells indicates that a tumor antigen cross-priming occurs in vivo following radiotherapy.…”

Section: Genetic Background and Clinical Outcomementioning

confidence: 99%

Prerequisites for the Antitumor Vaccine-Like Effect of Chemotherapy and Radiotherapy

Hannani

Sistigu²,

Kepp

et al. 2011

The Cancer Journal

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For a long time, anticancer therapies were believed to work (and hence convey a therapeutic benefit) either by killing cancer cells or by inducing a permanent arrest in their cell cycle (senescence). In both scenarios, the efficacy of anticancer regimens was thought to depend on cancer cell-intrinsic features only. More recently, the importance of the tumor microenvironment (including stromal and immune cells) has been recognized, along with the development of therapies that function by modulating tumor cell-extrinsic pathways. In particular, it has been shown that some chemotherapeutic and radiotherapeutic regimens trigger cancer cell death while stimulating an active immune response against the tumor. Such an immunogenic cell death relies on the coordinated emission of specific signals from dying cancer cells and their perception by the host immune system. The resulting tumor-specific immune response is critical for the eradication of tumor cells that may survive therapy. In this review, we discuss the molecular mechanisms that underlie the vaccine-like effects of some chemotherapeutic and radiotherapeutic regimens, with particular attention to the signaling pathways and genetic elements that constitute the prerequisites for immunogenic anticancer therapy.

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“…However, in this study better survival did not correlate with TKI-induced hypothyroidism. Retrospective analyses suggest that patients who experience immune-related adverse events, including endocrinopathies, may be more likely to benefit from anti-CTLA4-MAb therapy (107,231,232).…”

Section: Why Is It Important To Assess Thyroid Function In Cancer Patmentioning

confidence: 99%

Thyroid Dysfunction as an Unintended Side Effect of Anticancer Drugs

Torino

Barnabei²,

Paragliola

et al. 2013

Thyroid

104

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Current Experience With CTLA4-blocking Monoclonal Antibodies for the Treatment of Solid Tumors

Cited by 32 publications

References 93 publications

ENDOCRINE SIDE-EFFECTS OF ANTI-CANCER DRUGS: mAbs and pituitary dysfunction: clinical evidence and pathogenic hypotheses

ENDOCRINE SIDE-EFFECTS OF ANTI-CANCER DRUGS: mAbs and pituitary dysfunction: clinical evidence and pathogenic hypotheses

Prerequisites for the Antitumor Vaccine-Like Effect of Chemotherapy and Radiotherapy

Thyroid Dysfunction as an Unintended Side Effect of Anticancer Drugs

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