Seminars in oncology
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Seminars in oncology · Oct 2018
Review Meta AnalysisCurrent therapeutic options in metastatic castration-resistant prostate cancer.
The tumors of many patients with prostate cancer eventually become refractory to androgen deprivation therapy with progression to metastatic castration-resistant disease. Significant advances in the treatment of metastatic castration-resistant prostate cancer (mCRPC) have been made in recent years, and new treatment strategies have recently been made available. The aim of this report was to schematically review all the approved pharmacologic treatment options for patients with mCRPC through 2018, analyzing the efficacy and possible side effects of each therapy to assist clinicians in reaching an appropriate treatment decision. New biomarkers potentially of aid in the choice of treatment in this setting are also briefly reviewed. ⋯ Drug development efforts continue to attempt to prolong survival and improve quality of life in the mCRPC setting, with several therapeutic options available. Ongoing and future trials are needed to further assess the efficacy and safety of these new drugs and their interactions, along with the most appropriate sequencing.
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Seminars in oncology · Aug 2018
Review Meta AnalysisFDA analyses of survival in older adults with metastatic non-small cell lung cancer in controlled trials of PD-1/PD-L1 blocking antibodies.
Among patients with newly diagnosed non-small cell lung cancer (NSCLC), approximately 70% occur in those above 65 years of age and more than half are metastatic or locally advanced NSCLC. ⋯ Patients 65 and older with advanced and metastatic NSCLC, including those ≥75 years, seem to derive similar survival benefits from treatment with PD-1/PD-L1 blocking antibodies as patients <65 years of age. Patients 75 and older enrolled on these trials appear to tolerate PD-1/PD-L1 blocking antibodies and have a lower incidence of grade 3 or 4 treatment-emergent adverse events compared to the subgroup of patients <65 years of age.
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Seminars in oncology · Jun 2018
Meta AnalysisAvoiding chemotherapy for advanced nononcogene addicted NSCLC overexpressing PD-L1: Rule or option?
Patients with nonsmall-cell lung cancers expressing high levels of PD-L1 present a therapeutic dilemma for clinicians who have to choose between pembrolizumab as a single agent or in combination with chemotherapy. In order to help them as they ponder over this decision we performed a meta-analysis using the data available from randomized clinical trials that enrolled patients with untreated advanced nonsmall-cell lung cancers with PD-L1 expression level ≥50%. We evaluated interactions according to type of treatment-add-on strategy: pembrolizumab plus chemotherapy versus chemotherapy or head-to-head strategy: pembrolizumab alone versus chemotherapy. ⋯ A significant quantitative interaction favoring the add-on strategy was found for PFS and ORR (P < 0.001), with a HR for PFS of 0.36 with the add-on strategy and 0.65 in head-to head comparisons, and an OR for ORR of 5.35 and 1.58, respectively. In absence of planned prospective noninferiority trials addressing this issue, addition of chemotherapy to pembrolizumab appears to decrease tumor size and delay disease progression significantly more than pembrolizumab alone, but has no impact on OS. We conclude that the data support deciding between both treatment options on an individual basis by considering a patients' clinical status and disease characteristics.
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Side effects of immune checkpoint blockade are often said to be infrequent and usually mild. The uniqueness of endocrine immune-related adverse events is their non-reversibility, with incidence and prevalence destined to increase in the coming years, particularly if immunotherapy is used at earlier stages of neoplastic disease. Immune-related hypophysitis is one of these observed endocrine adverse events. ⋯ Management should include discontinuation of the immune checkpoint blockade, initiation of corticosteroid therapy and eventually hormone replacement therapy. Hypophysitis impacts treatment of the disease and usually requires long-term management of this irreversible side effect. A multidisciplinary team approach is merited to insure the correct diagnosis and management of immune-related hypophysitis.
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Seminars in oncology · Dec 2017
ReviewProteasome inhibitor-based therapy for treatment of newly diagnosed multiple myeloma.
Multiple myeloma is a hematologic malignancy that is unable to be cured and has significant impact throughout the world. Front line treatment has shifted but ultimately has landed on a bortezomib-based combination therapy. ⋯ Given the favorable response rates seen in phase II trials treating newly diagnosed myeloma, this combination is listed as a viable option for upfront treatment. This systematic review compares pharmacologic properties, clinical efficacy, and toxicities of carfilzomib- and bortezomib-based regimens.