cardiotoxicity with immune system targeting drugs a meta analysis of anti pd pd l1 immunotherapy randomized clinical trials

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A Phase I Study of the Non-Receptor Kinase Inhibitor Bosutinib in Combination with Pemetrexed in Patients with Selected Metastatic Solid Tumors

Src is overexpressed in various cancers, including 27% of non-small cell lung cancer NSCLC, and is correlated with poor clinical outcomes. We hypothesize that Src kinase inhibitors, including Bosutinib, may exhibit clinical synergy in combination with the antifolate drug pemetrexed. In this Phase I, dose-escalation, safety, and maximum tolerated dose (MTD)-determining study, 14 patients with advanced metastatic solid tumors that had progressed on “standard of care” chemotherapy were enrolled in a 3 + 3 dose escalation study. Oral Bosutinib was administered once daily beginning on day 1, where the first cohort started at an oral dose of 200 mg daily with pemetrexed 500 mg/m2 IV on a three-week schedule. The study’s primary objective was to determine the dose-limiting toxicity (DLT), the MTD of Bosutinib in combination with pemetrexed, and the type and frequency of adverse events associated with this treatment. Twelve patients were evaluable for response, including ten patients with adenocarcinoma of the lung, one patient with metastatic adenocarcinoma of the appendix, and one patient with urothelial carcinoma. The median number of Bosutinib and pemetrexed cycles received was 4 (range, 1–4). The MTD of oral Bosutinib in this combination was 300 mg daily. Two patients (17%) had a partial response (PR), and seven patients (58%) showed stable disease (SD) as the best response after the fourth cycle (end of treatment). One patient had disease progression after the second cycle, while three patients had disease progression after the fourth cycle. The two responders and the two patients with the longest stable disease duration or stabilization of disease following progression on multiple systemic therapies demonstrated Src overexpression on immunohistochemical staining of their tumor. The median progression-free survival (PFS) was 6.89 months (95% CI (3.48, 30.85)), and the median overall survival (OS) was 11.7 months (95% CI (3.87, 30.85)). Despite the limitations of this Phase I study, there appears to be potential efficacy of this combination in previously treated patients

Role of Targeted Therapy and Immune Checkpoint Blockers in Advanced Non‐Small Cell Lung Cancer: A Review

Advanced non-small cell lung cancer (NSCLC) is a complex disease comprising molecularly distinct tumor types, each with a unique biology that is becoming increasingly better characterized. The aim of this review is to present an optimized treatment schema and the accompanying diagnostic testing approach for patients with advanced NSCLC. There are a number of therapies currently approved for patients with advanced NSCLC, including agents that target particular oncogenic drivers, as well as immune checkpoint blockers (ICBs) that elicit an antitumor response. Identification of genetic alterations (e.g., epidermal growth factor receptor, anaplastic lymphoma kinase, reactive oxygen species proto-oncogene 1, B-Raf proto-oncogene) or programmed cell death ligand-1 expression levels in NSCLC requires diligent molecular testing at initial diagnosis and, in some cases, at disease progression to ensure the most efficacious treatment is delivered. Accurate molecular diagnostic testing, along with the careful selection of currently approved targeted agents, ICBs, or systemic chemotherapy, provides therapy that is personalized according to patients' needs to achieve the best possible outcome. Enrollment in clinical trials that further the development of tailored therapies is highly recommended at all stages of treatment. IMPLICATIONS FOR PRACTICE: Targeted therapies and immune checkpoint blockers provide effective and tailored options for patients with non-small cell lung cancer. Careful molecular analysis of tumor samples is necessary to identify the genetic alterations that are present, to ensure that each patient receives the most efficacious treatment for their specific tumor type. Personalized therapy provides each patient with the best probability for prolonged survival. Enrolling patients in clinical trials should be the first consideration before making each treatment decision

Influenza Vaccination in Cancer Patients Undergoing Systemic Therapy

Background Cancer patients often experience preventable infections, including influenza A and B. These infections can be a cause of significant morbidity and mortality. The increased risk of infection may be because of either cancer itself or treatment-induced immunosuppression. 1 Influenza immunization has been shown to decrease the risk of influenza infection in patients with intact immunity. 2 In cancer patients, active immunization has been shown to confer protective immunity against several infections at similar rates to healthy individuals, which has translated into decreased duration and severity of infection and potentially improved morbidity and mortality. 3 Objectives 1. To assess the efficacy of influenza vaccination in stimulating immunological response in patients with cancer during chemotherapy compared to control groups. 2. To assess the efficacy of influenza vaccination in preventing confirmed influenza and influenza-like illness and/or stimulating immunological response in children with cancer treated with chemotherapy, compared to placebo, no intervention, or different dosage schedules. 3. To determine the adverse effects associated with influenza vaccination in patients with cancer. Search Methods We searched MEDLINE/PubMed database for articles published from 1964 to 2013 using the search terms “cancer,” “adult,” “influenza vaccination,” and “chemotherapy.” Selection Criteria We included studies based on systematic sampling with defined clinical criteria irrespective of the vaccination status of cancer patients. Studies measure the serological response or clinical response to compare between the study group and the control group. Studies assessed the inactivated influenza vaccines and live attenuated influenza vaccine (LAIV) protective serological reaction and the clinical outcomes after vaccination. Data Collection and Analysis Two independent authors assessed the methodological quality of included studies and extracted data. Main Results We included 16 studies (total number of participants = 1,076). None of the included studies reported clinical outcomes. All included studies reported on influenza immunity and adverse reaction on vaccination. We included 6 solid tumor studies and 10 hematological studies. In 12 studies, the serological response to influenza vaccine was compared in patients receiving chemotherapy (n = 425) versus those not receiving chemotherapy (n = 376). In three studies, the serological responses to influenza vaccination in patients receiving chemotherapy are compared to that in healthy adult. Measures used to assess the serological responses included a four-fold rise increase in antibody titer development of hemagglutination inhibition (HI) titer >40, and pre- and post-vaccination geometric mean titers (GMTs). Immune responses in patients receiving chemotherapy were consistently weaker (four-fold rise of 17–52%) than in those who had completed chemotherapy (50–83%) and healthy patients (67–100%). Concerning adverse effects, oncology patients received influenza vaccine, and the side effects described were mild local reactions and low-grade fever. No life-threatening or persistent adverse effects were reported. Authors’ Conclusion Patients with solid and some of hematological tumors are able to mount a serological response to influenza vaccine, but it remains unclear how much this response protects them from influenza infection or its complications. Meanwhile, influenza vaccine appears to be safe in these patients. While waiting results of randomized controlled trials to give us more details about the clinical benefits of the influenza vaccination, the clinicians should consider the currently proved benefits of influenza vaccination on management of the cancer patients undergoing systematic chemotherapy such as decrease in the duration and severity of the of the disease, and significant decrease in influenza-associated morbidity and mortality in these high-risk patients.

Systemic Chemotherapy for Progression of Brain Metastases in Extensive-Stage Small Cell Lung Cancer

Lung cancer is the most common cause of cancer related mortality in men and women. Approximately 15% of lung cancers are small cell type. Chemotherapy and radiation are the mainstay treatments. Currently, the standard chemotherapy regimen includes platinum/etoposide. For extensive small cell lung cancer, irinotecan and cisplatin have also been used. Patients with relapsed small cell lung cancer have a very poor prognosis, and the morbidity increases with brain metastases. Approximately 10%–14% of small cell lung cancer patients exhibit brain metastases at the time of diagnosis, which increases to 50%–80% as the disease progresses. Mean survival with brain metastases is reported to be less than six months, thus calling for improved regimens. Here we present a case series of patients treated with irinotecan for progressive brain metastases in small cell lung cancer, which serves as a reminder of the role of systemic chemotherapy in this setting

Endobronchial lipoma

Endobronchial lipomas are rare benign lung tumors that can cause bronchial obstruction and parenchymal damage. While an uncommon etiology, they are often misdiagnosed due to a clinical presentation similar to obstructive pulmonary pathologies such as COPD and asthma. Upon review of English-language literature, under 50 cases of endobronchial lipomas were documented in the prior 10 years (2011-2021). There are no clear guidelines regarding the management of this particular entity, but typically interventional debulking is the treatment of choice. Here we present another unique case of endobronchial lipoma along with our diagnostic and therapeutic methodology. The patient underwent bronchoscopic debulking via a cryotherapy probe. Based on the histopathologic analysis, a diagnosis of endobronchial lipoma was made. Endobronchial lipomas must remain in any clinician’s differential when a patient presents with dyspnea. We report the unique location of this lipoma based on our literature review and the importance of investigating endobronchial lesions due to a possible diagnosis of endobronchial lipoma

Phase II Clinical Trial of Gefitinib for the Treatment of Chemonaïve Patients with Advanced Non-small Cell Lung Cancer with Poor Performance Status

Background Patients with advanced non-small cell lung cancer (NSCLC) have no curative treatment options; therefore, improving their quality of life (QOL) is an important goal. Gefitinib, an epidermal growth factor receptor (EGFR) inhibitor, is a safe oral agent that may be of benefit to a specific population of NSCLC. Patients and Methods A Phase II clinical trial included chemonaïve patients with advanced NSCLC and poor performance status (PS). Response rate, progression-free survival, overall survival, QOL using the Functional Assessment of Cancer Therapy – Lung (FACT-L) questionnaire, and Trial Outcome Index (TOI) were evaluated. Results Twelve out of 19 enrolled patients were evaluable. The median age for the evaluable patients was 68.8 years (59.7–74.6). Out of all the patients, 7 (58.3%) had adenocarcinoma and 5 (41.7%) had squamous cell carcinoma. The median duration of treatment was 62.5 days (26.5–115.0) in the evaluable patients. Grade 3/4 toxicities included fatigue, rash, diarrhea, and nausea. One patient had partial response, eight patients had stable disease (SD), and three patients progressed. The median overall survival for the evaluable population was 4.9 months (2.3–16). The median progression-free survival was 3.7 months (1.9–6.6). TOI was marginally associated with the overall survival, with a hazard ratio of 0.92 (95% confidence interval: 0.84, 1.0) ( P = 0.061). FACT-L score and the TOI were highly correlated ( r = 0.96, P < 0.0001). TOI scores were higher in African Americans compared to Caucasians and increased with age. Conclusion Our results suggest that gefitinib use in patients with NSCLC and poor PS may improve the QOL of older patients and African American patients