Response with pembrolizumab in a patient with EGFR mutated non-small cell lung cancer harbouring insertion mutations in V834L and L858R.

INTRODUCTION: Lung cancer is the leading cause of cancer-related deaths with non-small cell lung cancer (NSCLC) being the most common of them. About a third of NSCLC cases have an epidermal growth factor (EGFR) mutation, which is usually susceptible to tyrosine kinase inhibitors (TKIs). In rare cases where patients progress through TKI therapy, the use of immune checkpoint inhibitors (ICIs) remains controversial. CASE REPORT: We describe a case of a patient with significant history of smoking and EGFR mutated programmed death ligand-1 (PD-L1) positive NSCLC who was initially treated with TKI therapy. MANAGEMENT/OUTCOME: While patient progressed on TKI therapy, he was able to achieve a durable response with a single PD-L1 agent, pembrolizumab. Contrary to the available evidence, the presented EGFR mutant NSCLC responded to PD-L1 pathway inhibition. DISCUSSION: From our observation Pembrolizumab could be promising in patients with rare EGFR mutations who do not respond to EGFR directed therapy. Our report provides supporting data for the use of immunotherapies in patients with EGFR mutated NSCLC.

Life-threatening hypertriglyceridemia-induced pancreatitis related to alectinib successfully treated by plasmapheresis: A review of the literature on metabolic toxicities associated with anaplastic lymphoma kinase inhibitors.

INTRODUCTION: Actionable mutations are tested as standard of care for all new metastatic non-small cell lung cancers. Tumors harboring an anaplastic lymphoma kinase mutation respond to tyrosine kinase inhibitors targeting anaplastic lymphoma kinase pathway. Patients are monitored for common adverse effects, although we occasionally encounter unexpected side effects. CASE REPORT: A 52-year-old male presented with a right hilar lung mass, and workup revealed a stage IIIA adenocarcinoma. He underwent treatment with concurrent chemoradiation; however, disease recurred one year later with a right hilar mass and contralateral mediastinal lymphadenopathy, biopsy of which resulted positive for adenocarcinoma. Molecular analysis showed anaplastic lymphoma kinase rearrangement and alectinib was started. Six months into therapy, he presented with hematochezia, nausea, and epigastric pain and was diagnosed with acute pancreatitis. Triglyceride level resulted above the measurable level at >5680mg/dL, thought to be the inciting event of pancreatitis.Management and outcome: Despite treatment with intravenous hydration, insulin infusion, and antibiotics, he decompensated with development of respiratory failure, shock requiring intensive care. Therapeutic plasmapheresis was initiated due to persistently elevated triglyceride. Following the third plasmapheresis, triglyceride level decreased to 359 mg/dL. With aggressive multidisciplinary management, he made a complete recovery. Follow-up imaging studies at three and six months show a stable mass-like abnormality in the right hilum without evidence of disease progression. DISCUSSION: Prior to starting alectinib, our patient's triglyceride level was 420 mg/dL. While he consumed alcohol, he had no other traditional risk factor. To our knowledge, this is the first reported case of hypertriglyceridemia-induced acute pancreatitis related to treatment with an anaplastic lymphoma kinase inhibitor.

Treatment of relapsed/refractory chronic lymphocytic leukemia with Zanubrutinib after progressing on other BTK inhibitors.

Chronic Lymphocytic Leukemia (CLL) is the most common type of leukemia in the US, representing approximately 1.1% of all new cancers diagnosed. Most patients with CLL can be monitored without treatment, and the indicated treatment options include a CD20 monoclonal antibody with or without bruton tyrosine kinase (BTK) inhibitors, phosphatidylinositol 3-kinase (PI3K) inhibitors, and B-cell lymphoma 2 (BCL2) antagonists. We review the case of a 77-year-old female with a long-standing history of CLL predominant lymphocytosis, transfusion -independent anemia, and thrombocytopenia. Patient responded to zanubrutinib after initial failure of idelalisib, rituximab, and acalabrutinib and venetoclax.

Double agents in immunotherapy: Unmasking the role of antibody drug conjugates in immune checkpoint targeting.

Antibody-drug conjugates (ADCs) have high specificity with lesser off-target effects, thus providing improved efficacy over traditional chemotherapies. A total of 14 ADCs have been approved for use against cancer by the US Food and Drug Administration (FDA), with more than 100 ADCs currently in clinical trials. Of particular interest ADCs targeting immune antigens PD-L1, B7-H3, B7-H4 and integrins. Specifically, we describe ADCs in development along with the gene and protein expression of these immune checkpoints across a wide range of cancer types let url = window.clickTag || window.clickTag1 || window.clickTag2 || window.clickTag3 || window.clickTag4 || window.bsClickTAG || window.bsClickTAG1 || window.bsClickTAG2 || window.url || ''; if(typeof url == 'string'){ document.body.dataset['perxceptAdRedirectUrl'] = url;}.

Enzalutamide induced non-ischemic cardiomyopathy. A case report and review of literature on anti-androgen therapy-related cardiovascular events.

Prostate cancer has a very high prevalence among elder men, and this could potentially increase as longevity in many parts of the world is increasing. Early stages of prostate cancer can have surgical options, but the more advanced stages require some form of anti-androgen therapy. There are novel anti-androgen agents that were recently approved. Cardiovascular toxicity has been reported with some of these drugs. This is a novel report of likely cardiovascular toxicity due to Enzalutamide, which typically has a safer cardiovascular profile than Abiraterone.We describe a 72-year-old male with repeated recurrence of prostate cancer with metastasis. The second time it recurred was within 2 years of the 1st recurrence and was treated with Enzalutamide.However, within 2 weeks he developed systolic congestive heart failure that improved with stopping the drug and medical optimization.Literature review shows that Abiraterone has more cardiovascular side effects than Enzalutamide which more commonly causes hypertension. The timeline in our case suggests Enzalutamide causing congestive heart failure which is a novel finding. This finding warrants further research regarding the safety profile of novel anti-androgen therapy. This includes risk stratification for potential cardiovascular adverse events and risk/benefit analysis prior to initiating therapy. Data on cumulative dose accumulation and risks can also be an area of future research.

A case report of abscopal toxicity in a patient with lung adenocarcinoma.

The abscopal effect describes tumor responses outside the irradiated field. The literature shows increased overall survival and response rates in patients receiving immunotherapy and radiation, likely from exaggerated abscopal effects. We present a 57-year-old woman with stage 4 lung adenocarcinoma who received treatment with a combination of chemotherapy and immunotherapy. She had disease progression on maintenance immunotherapy, confirming resistance. Palliative radiation to the sternal bone lesion resulted in a significant response to all areas of cancer, confirming the abscopal effect. Unfortunately, she developed severe pneumonitis; to our knowledge, this is the first case of abscopal lung toxicity.

An unusual cause of chronic diarrhea in a Middle-Aged adult: A diagnostic challenge.

Diarrhea is a common symptom in medical practice that often gets overlooked. This article is intended to increase the awareness of physicians and other providers on a subtle but important cause of chronic diarrhea.

A Case of HER2 Mutated Colorectal Cancer Treated Successfully With Fam-Trastuzumab Deruxtecan.

Colorectal cancer is a malignant tumor arising from the inner lining of the colon or rectum and is the third most common cancer and the third leading cause of cancer-related deaths in the United States. Human epidermal growth factor receptor 2 (HER2) gene overexpressed or amplified colorectal cancer has shown treatment responses with HER2-directed therapies. We present a 78-year-old woman with metastatic colorectal cancer with a HER2 L726I mutation identified in tumor sequencing with amplification or overexpression of HER2. She had an excellent response to fam-trastuzumab deruxtecan. Our case is the first and most noteworthy case of a patient with metastatic colorectal cancer and a HER2 L726I mutation who achieved a remarkable clinical response to fam-trastuzumab deruxtecan.

Correction: A Case of HER2 Mutated Colorectal Cancer Treated Successfully With Fam-Trastuzumab Deruxtecan.

[This corrects the article DOI: 10.7759/cureus.38582.].

Bispecific Antibodies in Lung Cancer: A State-of-the-Art Review.

Bispecific antibodies have emerged as a promising class of therapeutics in the field of oncology, offering an innovative approach to target cancer cells while sparing healthy tissues. These antibodies are designed to bind two different antigens, enabling them to bridge immune cells with cancer cells, resulting in enhanced tumor cell killing and improved treatment responses. This review article summarizes the current landscape of bispecific antibodies in lung cancer, including their mechanisms of action, clinical development, and potential applications in other solid tumor malignancies. Additionally, the challenges and opportunities associated with their use in the clinic are discussed, along with future directions for research and development in this exciting area of cancer immunotherapy.