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 phase 2 trial of consolidation pembrolizumab following concurrent chemoradiation for patients with unresectable stage III non–small cell lung cancer: Hoosier Cancer Research Network LUN 14-179

Background Five-year overall survival (OS) for patients with unresectable stage III non–small cell lung cancer (NSCLC) is poor. Until recently, a standard of care was concurrent chemoradiation alone. Patients with metastatic NSCLC treated with anti–programmed death 1 antibodies have demonstrated improved OS. This trial evaluated pembrolizumab as consolidation therapy after concurrent chemoradiation in patients with unresectable stage III disease. Methods Patients with unresectable stage III NSCLC received concurrent chemoradiation with cisplatin and etoposide, cisplatin and pemetrexed, or carboplatin and paclitaxel and 59.4 to 66.6 Gy of radiation. Patients with nonprogression of disease were enrolled and received pembrolizumab (200 mg intravenously every 3 weeks for up to 12 months). The primary endpoint was the time to metastatic disease or death (TMDD). Secondary endpoints included progression-free survival (PFS) and OS. Results The median follow-up for 93 patients (92 for efficacy) was 32.2 months (range, 1.2-46.6 months). The median TMDD was 30.7 months (95% confidence interval [CI], 18.7 months to not reached), which was significantly longer than the historical control of 12 months (P < .0001). The median PFS was 18.7 months (95% CI, 12.4-33.8 months), and the median OS was 35.8 months (95% CI, 24.2 months to not reached). The 1-, 2-, and 3-year OS estimates were 81.2%, 62.0%, and 48.5%, respectively. Forty patients (43.5%) completed 12 months of treatment (median number of cycles, 13.5). Symptomatic pneumonitis (grade 2 or higher) was noted in 16 patients (17.2%); these cases included 4 grade 3 events (4.3%), 1 grade 4 event (1.1%), and 1 grade 5 event (1.1%). Conclusions Consolidation pembrolizumab after concurrent chemoradiation improves TMDD, PFS, and OS in comparison with historical controls of chemoradiation alone. Rates of grade 3 to 5 pneumonitis were similar to those reported with chemoradiation alone

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