Efficacy of immune checkpoint inhibitors in older adults with advanced stage cancers: A meta-analysis.

OBJECTIVES: There is uncertainty whether older patients derive a similar benefit from immune checkpoint inhibitors (ICI) as younger patients. We performed a meta-analysis of ICI trials in advanced cancers to better estimate treatment benefit in the older population. MATERIALS AND METHODS: We performed an electronic search for randomized trials of ICI, either as monotherapy or in combination with other agents. Hazard ratios (HR) for subgroups defined by different age cut-offs were extracted. Pooled overall survival (OS) treatment estimates were calculated using the inverse variance weighted method. RESULTS: In nineteen trials comparing ICI monotherapy versus non-ICI treatment, there was no significant treatment-age interaction (age ≥ 65 years: N = 6064, HR 0.73; age < 65 years: N = 7250, HR 0.79; P-interaction = 0.27). Findings were similar at older age cut-offs of 70 years (age ≥ 70 years: N = 433, HR = 0.93; age < 70 years: N = 169, HR = 0.95; P-interaction = 0.91) and 75 years (age ≥ 75 years: N = 139, HR = 0.75; age < 75 years: N = 1133, HR = 0.61; P-interaction = 0.72) respectively, and for trials of ICI combination therapy. CONCLUSION: ICI therapy improves OS in both younger and older patients with advanced cancers, and the magnitude of improvement does not depend on age. Patient selection for ICI therapy should be done based on performance status and adequate organ function independently of age.

The impact of ethnicity on efficacy and toxicity of cyclin D kinase 4/6 inhibitors in advanced breast cancer: a meta-analysis.

PURPOSE: Adding cyclin-dependent kinase (CDK) 4/6 inhibitor to endocrine therapy improves progression-free survival (PFS) in advanced breast cancer but the impact of ethnicity on efficacy and toxicity is unclear. We aimed to estimate the relative treatment efficacy and toxicity of endocrine therapy with and without CDK4/6 inhibitors, and compare between Asian/non-Asian subgroups. METHOD: This meta-analysis included published first-line randomized trials comparing CDK4/6 inhibitor-endocrine therapy versus endocrine monotherapy. Hazard ratios (HR) and 95% confidence intervals (CI) for the overall population and Asian/non-Asian subgroups were extracted. The inverse-variance-weighted method was used to pool treatment estimates of PFS. RESULTS: Four trials (N = 2499) were included. Patients received combination CDK4/6 inhibitor-endocrine therapy (N = 1441; ribociclib, [46.4%]; palbociclib, [30.8%]; or abemaciclib, [22.8%]) versus endocrine monotherapy (N = 1058). CDK4/6 inhibitor-endocrine therapy was associated with prolonged PFS compared with endocrine monotherapy (HR 0.56; 95% CI 0.50-0.62). In Asians (N = 492), PFS HR was 0.39 (95% CI 0.29-0.51, P < 0.0001). In non-Asians (N = 2007), PFS HR was 0.62 (95% CI 0.54-0.71, P < 0.0001). There was a significant treatment-by-ethnicity interaction (P = 0.002). Toxicity data by ethnic subgroup were only available from two trials (n = 1334) with no convincing evidence that the risk of toxicity between CDK4/6 inhibitor-endocrine therapy and endocrine monotherapy varied by ethnicity. CONCLUSION: Adding CDK4/6 inhibitor to endocrine therapy prolongs PFS compared to endocrine therapy alone as first-line treatment in advanced breast cancer. The magnitude of PFS benefit is ethnicity-dependent but there is no interethnic differences in relative treatment-related toxicities. These findings may assist in the design and interpretation of trials, inform economic analyses, and stimulate pharmacogenomic research.

Hepatotoxicity of targeted therapy for cancer.

INTRODUCTION: Understanding the mechanism of DILI with MTA, and how to avoid and manage these toxicities is essential for minimising inferior cancer treatment outcomes. An organised and comprehensive overview of MTA-associated hepatotoxicity is lacking; this review aims to fill the gap. AREAS COVERED: A literature review was performed based on published case reports and relevant studies or articles pertaining to the topics on PubMed. Food and Drug Administration drug information documents and search on the US National Library of Medicine LiverTox database was performed for all relevant MTA. EXPERT OPINION: MTA-associated hepatotoxicity is common but rarely fatal. The pattern of hepatotoxicity is predominantly idiosyncratic. Pharmacogenomics show potential in predicting patients at risk of poorly metabolising or developing immunoallergic responses to MTA, but prospective data is scant. Preventing reactivation of viral hepatitis using anti-viral drugs, and avoidance of drug combinations at high risk of negative interactions are the most readily preventable measures for DILI.

Piperacillin/tazobactam Induced Myelosuppression.

UNLABELLED: Neutropenia, secondary to immune destruction or maturation arrest, is the most commonly described adverse haematological effect of beta-lactam antibiotics. We describe a case of reversible pancytopenia, with evidence of hypocellular marrow, after a prolonged course of piperacillin/tazobactam for 26 days. KEYWORDS: Piperacillin; Tazobactam; Myelosuppression; Neutropenia.

A lady with unresolved loin pain.

A history of cardiac disease, especially atrial fibrillation, together with symptoms such as loin or abdominal pain, and accompanied by an elevated lactate dehydrogenase should prompt a computed tomography scan to exclude the diagnosis of acute renal infarction.