24-Month Overall Survival from KEYNOTE-021 Cohort G: Pemetrexed and Carboplatin with or without Pembrolizumab as First-Line Therapy for Advanced Nonsquamous Non–Small Cell Lung Cancer

Introduction Cohort G of KEYNOTE-021 (NCT02039674) evaluated the efficacy and safety of pembrolizumab plus pemetrexed-carboplatin (PC) versus PC alone as first-line therapy for advanced nonsquamous NSCLC. At the primary analysis (median follow-up time 10.6 months), pembrolizumab significantly improved objective response rate (ORR) and progression-free survival (PFS); the hazard ratio (HR) for overall survival (OS) was 0.90 (95% confidence interval [CI]: 0.42‒1.91). Herein, we present an updated analysis. Methods A total of 123 patients with previously untreated stage IIIB/IV nonsquamous NSCLC without EGFR and/or ALK receptor tyrosine kinase gene (ALK) aberrations were randomized 1:1 to four cycles of PC with or without pembrolizumab, 200 mg every 3 weeks. Pembrolizumab treatment continued for 2 years; maintenance pemetrexed was permitted in both groups. Eligible patients in the PC-alone group with radiologic progression could cross over to pembrolizumab monotherapy. p Values are nominal (one-sided p < 0.025). Results As of December 1, 2017, the median follow-up time was 23.9 months. The ORR was 56.7% with pembrolizumab plus PC versus 30.2% with PC alone (estimated difference 26.4% [95% CI: 8.9%‒42.4%, p = 0.0016]). PFS was significantly improved with pembrolizumab plus PC versus PC alone (HR = 0.53, 95% CI: 0.33‒0.86, p = 0.0049). A total of 41 patients in the PC-alone group received subsequent anti‒programmed death 1/anti‒programmed death ligand 1 therapy. The HR for OS was 0.56 (95% CI: 0.32‒0.95, p = 0.0151). Forty-one percent of patients in the pembrolizumab plus PC group and 27% in the PC-alone group had grade 3 to 5 treatment-related adverse events. Conclusions The significant improvements in PFS and ORR with pembrolizumab plus PC versus PC alone observed in the primary analysis were maintained, and the HR for OS with a 24-month median follow-up was 0.56, favoring pembrolizumab plus PC

A Case of Acute Spontaneous Tumor Lysis Syndrome and New Diagnosis of Burkitt’s Lymphoma

Introduction Tumor lysis syndrome is a well-described phenomenoncharacterized by elevated serum levels of calcium, uric acid,potassium, phosphate, and lactate dehydrogenase due to lysis oftumor cells and release of intracellular contents. Acute kidneyinjury may occur as the result of precipitation of intrarenalcalcium phosphate salts related to the rapid destruction ofa large number of tumor cells.1 Tumor lysis syndrome mostoften occurs during induction chemotherapy for aggressiveleukemia or lymphoma, particularly those with large tumorburden.1 While tumor lysis syndrome is more commonly seenin patients receiving chemotherapy, it can occur spontaneouslyand has been described in aggressive malignancies, such asAML,2 Burkitt’s lymphoma in children1 and adults,3 and insolid malignancies, such as breast cancer.4 This case describes apatient who presented with a neck mass and spontaneous tumorlysis syndrome. Case Presentation A 76-year-old male with a past medical history of hypertension,hyperlipidemia, and coronary artery disease presented withepistaxis and a neck mass that was first noted four weeks prior topresentation. In addition, the patient noticed gingival bleedingwhen brushing his teeth, malaise, decreased appetite, and nightsweats, all of which developed during the previous week. Hisexam was significant for an ulcer with scab on his left buccalmucosa, a 6-cm left neck mass that was firm and non-tender,and several areas of ecchymosis on his arms bilaterally. Therewas no axillary or inguinal lymphadenopathy. The remainder ofthe exam was unremarkable

Maintenance treatment after induction therapy in non-small cell lung cancer: latest evidence and clinical implications

Non-small cell lung cancer (NSCLC) is the leading cause of cancer death in the industrialized world. Despite significant progress in early stage disease, survival rates for advanced disease remain low. Maintenance therapy is a treatment strategy that has been investigated extensively in NSCLC. Therapies that have been studied in this setting in randomized trials to date include chemotherapy and molecularly targeted agents. Following the development of multiple new agents that show activity in NSCLC and have a tolerable side-effect profile, there has been increasing interest in utilizing them to maintain response to initial therapy after treatment with platinum-based doublets. Two effective strategies have evolved: continuation and switch maintenance. Despite improvements in progression-free survival and often overall survival on multiple clinical trials, there remains considerable controversy around this treatment paradigm. Here, we briefly outline the evolution of this treatment strategy and examine the available data, including recently updated data from the PARAMOUNT, AVAPERL, and PointBreak maintenance trials. Ultimately, the decision to use maintenance chemotherapy requires a nuanced discussion between the patient and physician that adequately assesses benefits of prolonged therapy and impact in terms of toxicity, quality of life, and financial cost

Histiocytic Sarcoma: A case of a 52-year-old female with two synchronous primary malignancies at presentation

Case Report A 52-year-old female with a past medical history of chronicobstructive pulmonary disease, coronary artery disease, andan 80-pack-year smoking history presented to the emergency room with complaints of right upper extremity weakness and imbalance while walking for the previous two days. She stated that the onset was abrupt and progressively worsening to the point where she could no longer lift her right upper extremityagainst gravity. She maintained the ability to move her hand and grasp, but admitted to decreased strength and decreased dexterity of her right hand. She denied changes in vision. She also denied having bowel or bladder incontinence. She has no known allergies and her only medications included occasional benzodiazepines for anxiety and acetaminophen/oxycodonefor low back pain. Her family history was notable only for lung cancer, which was the cause of death of her mother

Relevance of the Updated Recursive Partitioning Analysis (U-RPA) Classification in the Contemporary Care of Patients with Brain Metastases

Patients with brain metastases (BMETS) need information about the prognosis and potential value of treatment options to make informed therapeutic decisions, but tools to predict survival in contemporary practice are scarce. We propose an Updated Recursive Partitioning Analysis (U-RPA) instrument to predict survival and benefit from brain-directed treatment (BDT) of contemporary patients. This was a retrospective analysis of patients with BMETS treated between 2017 and 2019. With survival as the primary endpoint, we calculated the U-RPA and generated estimates using Kaplan–Meier curves and hazard ratios. Of 862 eligible patients, 752 received BDT and 110 received best supportive care (BSC). Median overall survival with BDT and BSC was 9.3 and 1.3 months, respectively. Patients in RPA class 1, 2A, 2B and 3 who underwent BDT had median survival of 28.1, 14.7, 7.6 and 3.3 months, respectively. The median survival for patients in RPA 3 who received BDT (n = 147), WBRT (n = 79) and SRS (n = 54) was 3.3, 2.9 and 4.1 months, respectively. The U-RPA defines prognosis estimates, independent of tumor type and treatment modality, which can assist to make value-based care treatment decisions. The prognosis for patients in U-RPA class 2B and 3 remains poor, with consideration for early palliative care involvement in these cases

Table_1_Association of sarcopenia with survival in advanced NSCLC patients receiving concurrent immunotherapy and chemotherapy.pdf

BackgroundFrailty, sarcopenia and malnutrition are powerful predictors of clinical outcomes that are not routinely measured in patients with non-small cell lung cancer (NSCLC). The primary aim of this study was to investigate the association of sarcopenia, determined by the psoas muscle index (PMI) with overall survival (OS) in patients with advanced NSCLC treated with concurrent immune checkpoint inhibitor (ICI) and chemotherapy (CTX).MethodsWe retrospectively reviewed data from a cohort of patients with locally advanced or metastatic NSCLC who were treated between 2015 and 2021 at the University of Virginia Medical Center. The cross-sectional area of the psoas muscle was assessed on CT or PET/CT imaging prior to treatment initiation. Multivariate analysis was performed using Cox proportional hazards regression models.ResultsA total of 92 patients (median age: 64 years, range 36-89 years), 48 (52.2%) men and 44 (47.8%) women, were included in the study. The median follow-up was 29.6 months. The median OS was 17.8 months. Sarcopenia, defined by a PMI below the 25th percentile, was associated with significantly lower OS (9.1 months in sarcopenic patients vs. 22.3 months in non-sarcopenic patients, P = 0.002). Multivariate analysis revealed that sarcopenia (HR 2.12, P = 0.0209), ECOG ≥ 2 (HR 2.88, P = 0.0027), prognostic nutritional index (HR 3.02, P = 0.0034) and the absence of immune related adverse events (HR 2.04, P = 0.0185) were independently associated with inferior OS.ConclusionsSarcopenia is independently associated with poor OS in patients with advanced NSCLC undergoing concurrent ICI and CTX.</p