Phase II Study of Docetaxel and Trametinib in Patients with KRAS Mutation Positive Recurrent Non-Small Cell Lung Cancer (NSCLC; SWOG S1507, NCT-02642042).

PURPOSE: Efficacy of MEK inhibitors in KRAS+ NSCLC may differ based on specific KRAS mutations and comutations. Our hypothesis was that docetaxel and trametinib would improve activity in KRAS+ NSCLC and specifically in KRAS G12C NSCLC. PATIENTS AND METHODS: S1507 is a single-arm phase II study assessing the response rate (RR) with docetaxel plus trametinib in recurrent KRAS+ NSCLC and secondarily in the G12C subset. The accrual goal was 45 eligible patients, with at least 25 with G12C mutation. The design was two-stage design to rule out a 17% RR, within the overall population at the one-sided 3% level and within the G12C subset at the 5% level. RESULTS: Between July 18, 2016, and March 15, 2018, 60 patients were enrolled with 53 eligible and 18 eligible in the G12C cohort. The RR was 34% [95% confidence interval (CI), 22-48] overall and 28% (95% CI, 10-53) in G12C. Median PFS and OS were 4.1 and 3.3 months and 10.9 and 8.8 months, overall and in the subset, respectively. Common toxicities were fatigue, diarrhea, nausea, rash, anemia, mucositis, and neutropenia. Among 26 patients with known status for TP53 (10+ve) and STK11 (5+ve), OS (HR, 2.85; 95% CI, 1.16-7.01), and RR (0% vs. 56%, P = 0.004) were worse in patients with TP53 mutated versus wild-type cancers. CONCLUSIONS: RRs were significantly improved in the overall population. Contrary to preclinical studies, the combination showed no improvement in efficacy in G12C patients. Comutations may influence therapeutic efficacy of KRAS directed therapies and are worthy of further evaluation. See related commentary by Cantor and Aggarwal, p. 3563.

Demographic Barriers for Genetic Testing in High-Risk Breast Cancer Patients in the Northern Michigan Area.

INTRODUCTION: The National Comprehensive Cancer Network (NCCN) has outlined guidelines for criteria regarding genetic testing for high-penetrance breast and/or ovarian cancer susceptibility genes. Due to the lack of availability of genetic counseling services in Northern Michigan prior to COVID-19, the utilization of genetic testing falls well below recommended guidelines. METHODS: Patients diagnosed with breast cancer in 2019 were randomly selected from Ascension Michigan's Northern Ministries Tumor Registry. A retrospective chart review was conducted. For patients who met NCCN criteria, their medical records were used to determine if genetic testing was recommended and if genetic testing was completed. Univariate (Crosstabs and t-tests) and multivariate tests with logistic regression were used to identify significant associations between the variables of interest. RESULTS: One hundred and two (102) patient charts were reviewed in this group; 55 (52.4%) were eligible by the NCCN guidelines for genetic testing. From this eligible subset of patients, only 29 were offered genetic testing, and only 21 were tested. The mean age of the patients offered genetic counseling was 56.2 years compared and 67.6 years in the group not offered counseling (p < 0.001). The patient's insurance type was an independent factor for obtaining genetic testing, specifically, the subgroup who had Medicare (OR = 0.73, CI = 0.01-0.54; p = 0.02). Patients insured through Medicare were less likely to obtain genetic testing after referral to a genetic counselor (p = 0.01). CONCLUSION: Genetic counseling for high-risk breast cancer patients is below average in Northern Michigan, likely related to lack of physician referral, poor availability of counseling services, low socioeconomic status as well as a lower level of concern in older ages.

Atezolizumab-Induced Bell's Palsy in a Patient With Small Cell Lung Cancer.

Immune checkpoint inhibitors are rapidly becoming popular therapeutic options for patients suffering from a number of malignancies. Atezolizumab is a programmed cell death ligand-1 inhibitor, and binding to this ligand decreases the ability of tumor cells to evade the immune system, resulting in self-tolerance. While inhibition of these molecules leads to increased T-cell destruction of tumor cells, it also may lead to autoimmune destruction of healthy cells. Neurotoxicity is a rare complication of immune checkpoint inhibitor therapy, and facial palsy as a complication of atezolizumab therapy has only been reported in one additional study. We present the case of a 68-year-old female with a history of small cell carcinoma of the lung presenting with sudden-onset facial palsy and numbness of the distal extremities in the setting of receiving atezolizumab immunotherapy. Our patient was managed with temporary cessation of her immunotherapy, oral prednisone, and supportive measures. Within 4 weeks, the patient had complete resolution of her facial palsy and was able to resume immunotherapy without further complication. Clinicians should be aware of this rare adverse effect in order to enact early management including temporary cessation of therapy to prevent morbidity in patients undergoing immunotherapy.

Polycythemia vera masked due to severe iron deficiency anemia.

Polycythemia vera is one of the chronic myeloproliferative diseases and very few patients present with its actual clinical manifestations. The most common findings are increased red cell mass and an increased leukocyte count with decreased erythropoietin. We present a case where there was a delay in the diagnosis of polycythemia because of menorrhagia in the past. On admission, the patient presented with elevated red and white blood cell counts, erythropoietin was low, and polycythemia was then suspected. A bcr-abl test was performed to rule out chronic myelogenous leukemia. JAK2 mutation was positive, and the patient was diagnosed with polycythemia vera.

Thalidomide-induced hemorrhagic rash in a patient with myelofibrosis and delta-granule storage pool disease.

Thalidomide is one of the immunomodulating agents used in current oncology practice. We present a case of hemorrhagic rash induced by thalidomide in a patient with delta granule storage pool disease. The patient was getting thalidomide for underlying myelofibrosis.

Docetaxel-induced hypersensitivity pneumonitis mimicking lymphangitic carcinomatosis in a patient with metastatic adenocarcinoma of the lung.

Docetaxel belongs to the taxane family of anti-cancer drugs, which are commonly used in non-small cell lung cancers. They stabilize microtubules by preventing depolymerization, resulting in cell death. Pneumonitis is an uncommon side effect of docetaxel. We report a case of docetaxel induced hypersensitivity pneumonitis mimicking lymphangitic carcinomatosis in a patient with metastatic adenocarcinoma of the lung.

Carboplatin-induced hematuria in a patient of breast carcinoma. A case report.

Platinum-based antineoplastic drugs are widely used in the treatment of solid tumors. Carboplatin, a second generation platinum compound, was developed to have less nonhematologic toxicity, in comparison with cisplatin. We report on a 34-year-old woman with breast cancer who developed gross hematuria after initiation of carboplatin-based chemotherapy. To our knowledge, there are very few cases reports of carboplatin-associated gross hematuria.

Acute dyspnea from treatment of AL amyloidisis with bortezomib.

Bortezomib with or without dexamethasone has been reported to be very effective and well tolerated in the treatment of AL amyloidosis. Commonly reported adverse effects are fatigue, nausea, vomiting, diarrhea, constipation, postural hypotension from autonomic neuropathy, peripheral neuropathy, thrombocytopenia and anemia. Dyspnea has been rarely reported as an adverse effect of bortezomib therapy in AL amyloidosis. We are reporting three case reports of patients suffering from AL amyloidodis, who had new onset acute dyspnea secondary to bortezomib treatment that required drug discontinuation. There might be some correlation between the AL amyloidosis disease and bortezomib associated dyspnea, but the pathophysiology is poorly understood.

New-onset acute interstitial lung disease after treatment with erlotinib in a patient with metastatic squamous cell carcinoma of the lung.

Erlotinib is a Human Epidermal Growth Factor Receptor Type 1/tyrosine kinase (EGFR) inhibitor, which is used for non-small-cell lung cancer treatment. Erlotinib usually has a favorable safety profile however; adverse events such as interstitial lung disease (ILD) have been reported in pivotal studies. ILD usually occurs weeks to months after initiating therapy with Erlotinib. We report a case of Erlotinib induced ILD presenting within 5 days of initiating treatment with Erlotinib.

Aggressive posttransplant lymphoproliferative disease in a renal transplant patient treated with alemtuzumab.

Post transplant lymphoproliferative disease (PTLD) is a rare but potentially fatal complication after solid organ transplantation. The risk of PTLD varies with type of organ transplant, Epstein-Barr virus serostatus of the donor and recipient, age, and intensity of immunosuppression. We report a case of a 45-year-old man who developed aggressive PTLD 7 months after receiving a cadaveric renal transplant. He received 30 mg alemtuzumab intravenously intraoperatively as induction immunosuppression followed by maintenance immunosuppression with tacrolimus and mycophenolate mofetil. The patient presented with intestinal perforation and gastrointestinal bleeding. Histopathology revealed Epstein-Barr virus-positive diffuse large B-cell lymphoma with a high mitotic index involving multiple segments of small and large intestines and leading to perforation of the ileum, jejunum, and cecum. The patient had Stage IV disease and treatment consisted of immunosuppression reduction and 375 mg/m rituximab weekly for four doses. Unfortunately, the patient had recurrent intestinal perforation followed by fatal gastrointestinal bleeding. There have been very few case reports of PTLD after alemtuzumab induction in renal transplant and the case discussed had simultaneous multiple perforations in the small intestine and colon.

Rapidly progressing glomerulonephritis secondary to henoch-schonlein purpura treated with mycophenolate mofetil: a case report with atypical etiology and presentation.

Henoch-Schonlein purpura (HSP) is an acute leukocytoclastic vasculitis that primarily affects children but also affects approximately 1% of adults. We discuss a case of HSP that started after pantoprazole ingestion. Clinical manifestation included terminal ileitis and rapidly progressing glomerulonephritis. To our knowledge, this is the first reported case of HSP secondary to pantoprazole ingestion. The patient presented with renal failure requiring hemodialysis and was initially unresponsive to intravenous pulse steroids. The patient was treated with mycophenolate mofetil, and his renal function recovered. There are limited data regarding use of mycophenolate mofetil for treating crescentic glomerulonephritis secondary to HSP.