Brief Report: Safety of Pulse-Dose Osimertinib for Treatment of Leptomeningeal Disease or Refractory Brain Metastases in EGFR-Mutated Nonsmall Cell Lung Cancer.

Purpose: EGFR-mutated (EGFRm) NSCLC is associated with high incidence of brain metastases and leptomeningeal disease (LMD), for which effective systemic options beyond osimertinib 80 and 160 mg daily are limited. While there is some evidence for high-dose pulse administration of earlier-generation EGFR tyrosine kinase inhibitors (EGFK-TKIs), data for pulse-dose osimertinib are limited.

Methods: This multicenter retrospective case series included patients with EGFRm NSCLC with LMD or parenchymal brain metastases treated with pulse-dose osimertinib (400-560 mg once every 5-7 days) for central nervous system (CNS) progression, with or without other concurrent therapies.

Afatinib and Necitumumab in -Mutant NSCLC with Acquired Resistance to Tyrosine Kinase Inhibitors.

Introduction: Although tyrosine kinase inhibitors (TKIs) are effective against NSCLC harboring sensitizing gene mutations, acquired resistance is inevitable. Preclinical studies suggest that combining EGFR TKI and monoclonal antibody therapies may have activity in mutated NSCLC that has progressed on TKI therapy alone. Therefore, we prospectively evaluated afatinib plus necitumumab in patients with mutated NSCLC.

A Phase 2 Single-Arm Trial of High-Dose Precision Targeted Radiation Therapy Added to Immunotherapy for Patients With Metastatic Non-Small Cell Lung Cancer.

Purpose: For metastatic non-small cell lung cancer, the addition of radiation therapy (RT) to immune checkpoint inhibitor (ICI) therapy could have synergistic anti-cancer effects and address the most threatening tumors. We posited that the addition of high-dose RT to ICI could prolong progression-free survival (PFS).

Methods And Materials: In this single-arm phase 2 trial, 45 patients with metastatic non-small cell lung cancer who had received an anti-PD-1/anti-PD-L1 ICI for 4+ weeks were enrolled from July 2017 to May 2021.

Tyrosine Kinase Inhibitors With and Without Up-Front Stereotactic Radiosurgery for Brain Metastases From and Oncogene-Driven Non-Small Cell Lung Cancer (TURBO-NSCLC).

Purpose: Newer-generation tyrosine kinase inhibitors (TKIs) for non-small cell lung cancer (NSCLC) with epidermal growth factor receptor () mutations and anaplastic lymphoma kinase () rearrangements have demonstrated high CNS activity. The optimal use of up-front stereotactic radiosurgery (SRS) for brain metastases (BM) in patients eligible for CNS-penetrant TKIs is controversial, and data to guide patient management are limited.

Materials And Methods: Data on TKI-naïve patients with EGFR- and ALK-driven NSCLC with BM treated with CNS-penetrant TKIs with and without up-front SRS were retrospectively collected from seven academic centers in the United States.

Patient Selection and Outcomes for Hypofractionated Accelerated Radiation and Concurrent Chemotherapy for Non-Small-Cell Lung Cancer.

Purpose/objectives: Adoption of hypofractionated accelerated radiation therapy (HART) with concurrent chemotherapy has been limited by toxicity concerns. We aimed to describe outcomes of patients treated with HART and concurrent chemotherapy and to evaluate dosimetry to organs at risk to guide patient selection.

Materials/methods: We evaluated a retrospective cohort of NSCLC patients treated with concurrent chemotherapy with HART (>2.

Personalized Accelerated ChEmoRadiation (PACER) for Lung Cancer: Protocol for a Bayesian Optimal Phase I/II Trial.

Introduction: Prior attempts to escalate radiation dose for non-small cell lung cancer (NSCLC) have not improved survival. Given the high risk for cardiopulmonary toxicity with treatment and heterogenous presentation of locally advanced NSCLC, it is unlikely that a single dose regimen is optimal for all patients. This phase I/II trial aims to evaluate a novel treatment approach where the level of accelerated hypofractionation is determined by the predicted toxicity from dose to organs at risk (OARs).

Overall Survival Among Patients With De Novo Stage IV Metastatic and Distant Metastatic Recurrent Non-Small Cell Lung Cancer.

Importance: Despite recent breakthroughs in therapy, advanced lung cancer still poses a therapeutic challenge. The survival profile of patients with metastatic lung cancer remains poorly understood by metastatic disease type (ie, de novo stage IV vs distant recurrence).

Objective: To evaluate the association of metastatic disease type on overall survival (OS) among patients with non-small cell lung cancer (NSCLC) and to identify potential mechanisms underlying any survival difference.

Simultaneous Cases of Carfilzomib-Induced Thrombotic Microangiopathy in 2 Patients With Multiple Myeloma.

Background: In patients with multiple myeloma, thrombotic microangiopathy is a rare adverse event associated with proteasome inhibitors, such as bortezomib, carfilzomib, and ixazomib.

Case Presentation: Two patients with multiple myeloma who presented with carfilzomib-induced thrombotic microangiopathy received eculizumab with subsequent stabilization of renal function.

Conclusions: Given the overall rarity of this adverse event, the simultaneous presentation of these 2 cases was unexpected.

Use of Machine Learning and Lay Care Coaches to Increase Advance Care Planning Conversations for Patients With Metastatic Cancer.

Purpose: Patients with metastatic cancer benefit from advance care planning (ACP) conversations. We aimed to improve ACP using a computer model to select high-risk patients, with shorter predicted survival, for conversations with providers and lay care coaches. Outcomes included ACP documentation frequency and end-of-life quality measures.

Novel HIVEP1-ALK fusion in a patient with lung adenocarcinoma demonstrating sensitivity to alectinib: a case report.

Background: Anaplastic lymphoma kinase (ALK) fusion is an important oncogenic driver in non-small cell lung cancer (NSCLC). Reports on the intergenic region (IGR) as an ALK fusion partner are rare. Here, we report the case of a patient with advanced NSCLC harboring a human immunodeficiency virus type I enhancer binding protein 1 (HIVEP1)-ALK fusion that responded effectively to alectinib.

Management of brain metastases in lung cancer: evolving roles for radiation and systemic treatment in the era of targeted and immune therapies.

Brain metastases are a common occurrence in both non-small cell and small cell lung cancer with the potential to affect quality of life and prognosis. Due to concerns about the accessibility of the central nervous system by systemic chemotherapy agents, the management of brain metastases has historically relied on local therapies including surgery and radiation. However, novel targeted and immune therapies that improve overall outcomes in lung cancer have demonstrated effective intracranial activity.

Brain Metastases in EGFR- and ALK-Positive NSCLC: Outcomes of Central Nervous System-Penetrant Tyrosine Kinase Inhibitors Alone Versus in Combination With Radiation.

Introduction: Management of central nervous system (CNS) metastases in patients with driver-mutated NSCLC has traditionally incorporated both tyrosine kinase inhibitors (TKIs) and intracranial radiation. Whether next generation, CNS-penetrant TKIs can be used alone without upfront radiation, however, remains unknown. This multi-institutional retrospective analysis aimed to compare outcomes in patients with EGFR- or ALK-positive NSCLC who received CNS-penetrant TKI therapy alone versus in combination with radiation for new or progressing intracranial metastases.

Safety of lorlatinib following alectinib-induced pneumonitis in two patients with -rearranged non-small cell lung cancer: a case series.

Drug-induced interstitial lung disease (DI-ILD) is a rare adverse event associated with targeted therapies that inhibit the anaplastic lymphoma kinase (ALK) protein. Although newer-generation ALK inhibitors such as alectinib significantly improve survival in metastatic rearranged non-small cell lung cancer (NSCLC), the risk of DI-ILD is similar to that of earlier-generation therapies. Lorlatinib is a third-generation ALK inhibitor that is active in patients with metastatic NSCLC whose tumors have developed secondary resistance to alectinib.

Advances in the Treatment of Stage III Non-Small Cell Lung Cancer.

Treatment of stage III non-small cell lung cancer (NSCLC) traditionally has involved combinations of chemotherapy, radiation, and surgical resection. Although the multimodality approach remains standard, only a fraction of patients with stage III lung cancer can undergo complete resection, and long-term prognosis remains poor. The PACIFIC trial generated significant enthusiasm when it demonstrated that the programmed death ligand-1 inhibitor, durvalumab, improved survival in patients with unresectable stage III NSCLC after completion of definitive concurrent chemoradiation.

Real-world treatment patterns and survival of patients with BRAF V600-mutated metastatic non-small cell lung cancer.

Introduction: Clinical outcomes data on BRAF-mutated non-small cell lung cancer (NSCLC) patients treated in routine practice is limited. To address this gap, we described treatment patterns and survival in a cohort of these patients evaluated/treated at 7 US academic cancer centers during 2009-2016.

Methods: This was a retrospective chart review.

Natural Disease History, Outcomes, and Co-mutations in a Series of Patients With BRAF-Mutated Non-small-cell Lung Cancer.

Background: BRAF mutations occur in 1% to 4% of non-small-cell lung cancer (NSCLC) cases. Previous retrospective studies have reported similar outcomes for BRAF-mutated NSCLC as compared with wild-type tumors without a known driver mutation or tumors harboring other mutations. However, select cases of prolonged survival have also been described, and thus, the natural history of BRAF-mutated NSCLC remains an area of ongoing study.

Targeting -Mutant Non-Small Cell Lung Cancer: From Molecular Profiling to Rationally Designed Therapy.

Unlabelled: Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related deaths globally. However, the identification of oncogenic driver alterations involved in the initiation and maintenance of NSCLC, such as epidermal growth factor receptor mutations and anaplastic lymphoma kinase translocation, has led to the development of novel therapies that directly target mutant proteins and associated signaling pathways, resulting in improved clinical outcomes. As sequencing techniques have improved, the molecular heterogeneity of NSCLC has become apparent, leading to the identification of a number of potentially actionable oncogenic driver mutations.