Journal for immunotherapy of cancer
-
J Immunother Cancer · Jul 2019
A phase I study of the PD-L1 inhibitor, durvalumab, in combination with a PARP inhibitor, olaparib, and a VEGFR1-3 inhibitor, cediranib, in recurrent women's cancers with biomarker analyses.
Strategies to improve activity of immune checkpoint inhibitors are needed. We hypothesized enhanced DNA damage by olaparib, a PARP inhibitor, and reduced VEGF signaling by cediranib, a VEGFR1-3 inhibitor, would complement anti-tumor activity of durvalumab, a PD-L1 inhibitor, and the 3-drug combination would be tolerable. ⋯ The RP2D is tolerable and has preliminary activity in recurrent women's cancers. A phase 2 expansion study is now enrolling for recurrent ovarian cancer patients.
-
J Immunother Cancer · Jul 2019
Clinical TrialThe Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of squamous cell carcinoma of the head and neck (HNSCC).
Head and neck cancers, including those of the lip and oral cavity, nasal cavity, paranasal sinuses, oropharynx, larynx and nasopharynx represent nearly 700,000 new cases and 380,000 deaths worldwide per annum, and account for over 10,000 annual deaths in the United States alone. Improvement in outcomes are needed for patients with recurrent and or metastatic squamous cell carcinoma of the head and neck (HNSCC). In 2016, the US Food and Drug Administration (FDA) granted the first immunotherapeutic approvals - the anti-PD-1 immune checkpoint inhibitors nivolumab and pembrolizumab - for the treatment of patients with recurrent squamous cell carcinoma of the head and neck (HNSCC) that is refractory to platinum-based regimens. ⋯ These consensus guidelines serve as a foundation to assist clinicians' understanding of the role of immunotherapies in this disease setting, and to standardize utilization across the field for patient benefit. Due to country-specific variances in approvals, availability and regulations regarding the discussed agents, this panel focused solely on FDA-approved drugs for the treatment of patients in the U. S.
-
J Immunother Cancer · Jul 2019
Case ReportsIsolated neutropenia as a rare but serious adverse event secondary to immune checkpoint inhibition.
Compared to conventional chemotherapy, Immune checkpoint inhibitors (ICI) are known to have a distinct toxicity profile commonly identified as immune-related adverse events (irAEs). These irAEs that are believed to be related to immune dysregulations triggered by ICI can be serious and lead to treatment interruptions and in severe cases, precipitate permanent discontinuation. Isolated neutropenia secondary to ICI has been rarely documented in the literature and needs further description. We report a case of pembrolizumab related severe isolated neutropenia in a patient with metastatic non-small cell lung cancer. We were also able to obtain serial blood and plasma-based biomarkers for this patient during treatment and during neutropenia to understand trends that may correlate with the irAE. In addition we summarize important findings from other studies reporting on ICI related neutropenia. ⋯ Neutropenia as an isolated irAE secondary to ICI is rare but represents a severe toxicity that needs early recognition and can often result in treatment discontinuations. Careful monitoring of these patients with the prompt initiation of immunosuppressive and supportive measures to promote rapid recovery as well as prevent and treat infectious complications should be part of the management algorithms. Serial monitoring of blood and plasma-based biomarkers from more extensive studies may help in identifying patients at risk for irAEs and thus guide patient selection for ICI.
-
J Immunother Cancer · Jul 2019
Hypothesis: does adrenalitis caused by immune checkpoint-inhibitors put melanoma patients at an elevated risk for recurrence?
Primary adrenal failure (Addison's disease) is a rare complication of immune checkpoint inhibitor (ICI) therapy. Untreated - and also sometimes under adequate hydrocortisone replacement therapy - the levels of ACTH (Adrenocorticotropic hormone) and MSH (Melanocyte stimulating hormone) are elevated. This may be a reason for concern in patients with malignant melanoma (MM): Melanocortin receptors bind to ACTH and the different isoforms of MSH. ⋯ Since it is also involved in the proliferation of melanoma cells, the elevated levels of ACTH and its proteolytic cleavage product α-MSH typical for primary failure may lead to an activation of the receptor and, thus, put MM patients that suffered from primary adrenal failure after ICI therapy at an elevated risk for recurrence or an unfavorable course of the disease. Novel dual-release hydrocortisone therapy results in lower ACTH (and most probably lower α-MSH) levels due to the more physiological mode of hydrocortisone release. Given that the concern raised in this hypothesis is confirmed in future investigations, patients who suffer from primary adrenal failure after ICI therapy may benefit from a dual-release hydrocortisone replacement regimen.
-
J Immunother Cancer · Jun 2019
Retracted PublicationResponse to targeted therapy or chemotherapy following immunotherapy in patients with gastrointestinal cancers - a case series.
In non-small cell lung cancer, response rates to chemotherapy given after immune checkpoint inhibitors has been reported to be higher compared to response rates to chemotherapy given before immune checkpoint inhibitors. However, this phenomenon has not been reported in patients with gastrointestinal cancers nor with the use of multi-targeted kinase inhibitors. ⋯ We postulate that the sequencing of immune checkpoint inhibitors prior to other forms of systemic therapy may potentially lead to an immunomodulatory effect in gastrointestinal cancers with potential improvement in response rates.