Response to osimertinib in a colorectal cancer patient with an EGFR T790M mutation: A case report.

BACKGROUND: Although common in lung cancer, somatic epidermal growth factor receptor (EGFR) mutations are rarely found in colorectal cancer, occurring in approximately 3% of cases. Treatment with anti-EGFR antibodies is commonplace, but EGFR tyrosine kinase inhibitors are not standard treatments in colorectal cancer. Here we report a case of sustained response to osimertinib in a colorectal cancer patient with an EGFR T790M mutation on cell-free DNA analysis. CASE SUMMARY: A 72-year old woman with a past medical history of post-polio syndrome confined to a wheelchair, scoliosis and hypothyroidism presented with metastatic sigmoid colon adenocarcinoma with hepatic metastases. Next generation sequencing revealed a RAS/RAF wild-type, microsatellite stable, PD-L1 negative malignancy. Mutations in TP3 and APC were also identified, as well as EGFR amplification. Cell-free DNA analysis revealed an EGFR T790M mutation. She was unable to tolerate first-line treatment with panitumumab, 5-fluorouracil and leucovorin, progressed on second-line treatment with trifluridine/tipiracil plus bevacizumab, and was unable to tolerate third-line treatment with regorafenib. She was started on fourth-line treatment with off-label osimertinib, with clinical response - decrease in size of hepatic metastases and a pericardial effusion. She remained on treatment with osimertinib for seven months. CONCLUSION: This case shows the benefit of multi-gene sequencing assays to identify potential therapeutic options in patients with refractory disease.

Molecular Tumor Board Case Series: Targeting KRAS G12C in Lung Cancer.

Next-generation sequencing (NGS) identifies biomarkers with prognostic and predictive importance in patients with cancer. The enormous amounts of data generated by comprehensive NGS adds complexity to the identification of valid drug therapy targets. Rapid progress made in targeted drug development creates the need for novel methods to access these treatments for patients. Molecular tumor boards (MTB) not only aid in identifying targetable gene mutations by carefully reviewing NGS data, they can also take lead in creating patient access to the appropriate targeted therapy. Here we describe two patients with Kirsten Rat Sarcoma (KRAS) G12C mutation positive lung adenocarcinoma for whom MTB was able to procure AMG510 or sotorasib, a covalent KRAS G12C inhibitor, by expanded access program ahead of FDA approval.

Germline BRCA-Mutated HER2-Negative Advanced Breast Cancer: Overcoming Challenges in Genetic Testing and Clinical Considerations When Using Talazoparib.

Genetic testing is essential to the diagnosis and management of patients with breast cancer. For example, women who carry mutations in BRCA1/2 genes have an increased lifetime risk of breast cancer and the presence of these mutations may sensitize the patient to treatment with poly(ADP-ribose) polymerase (PARP) inhibitors. Two PARP inhibitors are approved by the US Food and Drug Administration for patients with germline BRCA-mutated advanced breast cancer (olaparib and talazoparib). The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Breast Cancer (Version 2.2023) recommend that all patients with recurrent or metastatic breast cancer (mBC) be assessed for the presence of germline BRCA1/2 mutations. However, many women eligible for genetic testing do not receive it. Here, we provide our perspectives on both the importance of genetic testing and the challenges patients and community clinicians may face when trying to access genetic testing. We also present a hypothetical case study involving a female patient with germline BRCA-mutated human epidermal growth factor receptor 2 (HER2)-negative mBC to highlight potential clinical considerations on the use of talazoparib, including the decision to initiate therapy, dosing considerations, potential drug-drug interactions, and managing side effects. This case illustrates the benefits of a multidisciplinary approach to managing patients with mBC and involving the patient in the decision-making process. This patient case is fictional and does not represent events or a response from an actual patient; this fictional case is for educational purposes only.

Molecular Tumor Board Case Series: Targeted Treatments For Cancer And Their Toxicities: Amivantamab-Induced Linear IgA Bullous Dermatosis.

In the era of targeted treatments based on next generation sequencing (NGS) analysis, clinicians must be diligent in aligning patients with treatments giving them the best chance of survival while weighing the risk of toxicity caused by agents targeting specific gene mutations. In this case, we describe a patient with Epidermal Growth Factor Receptor (EGFR) exon 20 insertion mutation positive recurrent lung adenocarcinoma who received amivantamab and experienced severe dermatologic toxicity.

Bridging the Gap: Innovative 'Center for Precision Oncology' in Missouri.

Background: Next generation sequencing (NGS) has become standard practice for identification and treatment of targetable driver mutations in advanced cancer. However, NGS interpretation of clinical applicability can be challenging to clinician, with potential impact on patient's outcome. Specialized precision medicine services are poised to bridge this gap by creating collaborative frameworks to formulate and deliver genomic patient care plans. Methods: Saint Luke's Cancer Institute in Kansas City, Missouri, (SLCI) instituted the Center for Precision Oncology (CPO) in 2017. The program accepts patient referrals for a multidisciplinary molecular tumor board and offers CPO clinic visits. An Institutional Review Board-approved molecular registry was initiated. It catalogues genomic files along with patient demographics, treatment and outcomes. CPO patient volumes, recommendation acceptance, clinical trial matriculation and funding for drug procurement were closely tracked. Results: In 2020 there were 93 referrals to the CPO with 29 patient clinic visits. 20 patients matriculated to CPO-recommended therapies. Two patients were successfully enrolled in Expanded Access Programs (EAPs). CPO successfully procured eight off-label treatments. Treatments initiated per CPO recommendations totaled over $1 million in drug costs. Conclusion: Precision medicine services are essential tool for oncology clinicians. In addition to expert NGS analysis interpretation, precision medicine programs provide crucial multidisciplinary support for patients to understand the implications of their genomic report and pursue targeted treatment as indicated. Molecular registries associated with these services offer valuable opportunities for research.

Squamous cell carcinoma of the lung: improving the detection and management of immune-related adverse events.

INTRODUCTION: Immune checkpoint inhibitors (ICIs) have revolutionized treatment for patients with non-small lung cancer (NSCLC). Currently approved ICIs are monoclonal antibodies that target programmed death receptor 1 (PD-1), its ligand PD-L1, or CTLA-4. With ICIs comes a novel collection of toxicities: immune-related adverse events (IRAEs). Management of IRAEs requires multidisciplinary expertise. We review the biology of IRAEs and their management in patients with squamous NSCLC. AREAS COVERED: We review the pathophysiology of ICIs and IRAEs. For IRAEs related to squamous NSCLC, Cochrane Central, EMBASE, and PubMed were queried for trials with patients with squamous cell carcinoma or adenocarcinoma histology, who were assessed for incidence rates of IRAEs. Thirteen trials met inclusion criteria. National guidelines are reviewed to outline management strategies for IRAEs. EXPERT OPINION: IRAEs are unique compared to standard chemotherapy. As the role of ICIs expand across all stages of squamous cell NSCLC and with different combinations of antineoplastics, management of IRAEs will become crucial. Optimal management of IRAEs requires multidisciplinary teamwork. Further investigation into the pathophysiology of IRAEs can enhance current management strategies.

Current updates in management of Clostridium difficile infection in cancer patients.

BACKGROUND: Clostridium difficile infection (CDI) is a significant health burden, now recognized as the leading cause of acquired diarrhea in patients receiving antibiotic therapy. Complications of infection with this pathogen include severe diarrhea, causing electrolyte imbalances, dehydration, hemodynamic instability, toxic megacolon, shock, and death. Hence it is extremely paramount to stay updated on management options for this infection, especially in cancer patients. REVIEW: This article presents an in-depth review of literature on the treatment modalities available for CDI in cancer patients. Relevant articles highlighting therapeutic and symptomatic management of CDI patients with underlying malignancy have been summarized. CONCLUSIONS: Despite the current options available, more studies are needed to assess the newer therapeutic options that are being employed for populations other than cancer patients.