Efficacy and Safety of Adagrasib plus Cetuximab in Patients with KRASG12C-Mutated Metastatic Colorectal Cancer.

Unlabelled: Adagrasib, an irreversible, selective KRASG12C inhibitor, may be an effective treatment in KRASG12C-mutated colorectal cancer, particularly when combined with an anti-EGFR antibody. In this analysis of the KRYSTAL-1 trial, patients with previously treated KRASG12C-mutated unresectable or metastatic colorectal cancer received adagrasib (600 mg twice daily) plus cetuximab. The primary endpoint was objective response rate (ORR) by blinded independent central review.

Selective Personalized RadioImmunotherapy for Locally Advanced Non-Small-Cell Lung Cancer Trial (SPRINT).

Purpose: Standard therapy for locally advanced non-small-cell lung cancer (LA-NSCLC) is concurrent chemoradiotherapy followed by adjuvant durvalumab. For biomarker-selected patients with LA-NSCLC, we hypothesized that sequential pembrolizumab and risk-adapted radiotherapy, without chemotherapy, would be well-tolerated and effective.

Methods: Patients with stage III NSCLC or unresectable stage II NSCLC and an Eastern Cooperative Oncology Group performance status of 0-1 were eligible for this trial.

Amivantamab plus Chemotherapy in NSCLC with Exon 20 Insertions.

Background: Amivantamab has been approved for the treatment of patients with advanced non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor () exon 20 insertions who have had disease progression during or after platinum-based chemotherapy. Phase 1 data showed the safety and antitumor activity of amivantamab plus carboplatin-pemetrexed (chemotherapy). Additional data on this combination therapy are needed.

Clinical and Genomic Features of Response and Toxicity to Sotorasib in a Real-World Cohort of Patients With Advanced -Mutant Non-Small Cell Lung Cancer.

Purpose: With the recent approval of the KRAS G12C inhibitor sotorasib for patients with advanced -mutant non-small cell lung cancer (NSCLC), there is a new need to identify factors associated with activity and toxicity among patients treated in routine practice.

Materials And Methods: We conducted a multicenter retrospective study of patients treated with sotorasib outside of clinical trials to identify factors associated with real-world progression free survival (rwPFS), overall survival (OS), and toxicity.

Results: Among 105 patients with advanced -mutant NSCLC treated with sotorasib, treatment led to a 5.

Intracranial Efficacy of Adagrasib in Patients From the KRYSTAL-1 Trial With -Mutated Non-Small-Cell Lung Cancer Who Have Untreated CNS Metastases.

JCO Patients with Kirsten rat sarcoma viral oncogene homolog ()-mutated non-small-cell lung cancer (NSCLC) and untreated CNS metastases have a worse prognosis than similar patients without mutations. Adagrasib has previously demonstrated CNS penetration preclinically and cerebral spinal fluid penetration clinically. We evaluated adagrasib in patients with -mutated NSCLC and untreated CNS metastases from the KRYSTAL-1 trial (ClinicalTrials.

Adagrasib in Advanced Solid Tumors Harboring a Mutation.

Purpose: Adagrasib, a KRAS inhibitor, has demonstrated clinical activity in patients with -mutated non-small-cell lung cancer (NSCLC) and colorectal cancer (CRC). mutations occur rarely in other solid tumor types. We report evaluation of the clinical activity and safety of adagrasib in patients with other solid tumors harboring a mutation.

Management of infusion-related reactions (IRRs) in patients receiving amivantamab in the CHRYSALIS study.

Background: Amivantamab, a fully humanized EGFR-MET bispecific antibody, has antitumor activity in diverse EGFR- and MET-driven non-small cell lung cancer (NSCLC) and a safety profile consistent with associated on-target activities. Infusion-related reaction(s) (IRR[s]) are reported commonly with amivantamab. We review IRR and subsequent management in amivantamab-treated patients.

Adagrasib in Non-Small-Cell Lung Cancer Harboring a Mutation.

Background: Adagrasib, a KRAS inhibitor, irreversibly and selectively binds KRAS, locking it in its inactive state. Adagrasib showed clinical activity and had an acceptable adverse-event profile in the phase 1-1b part of the KRYSTAL-1 phase 1-2 study.

Methods: In a registrational phase 2 cohort, we evaluated adagrasib (600 mg orally twice daily) in patients with -mutated non-small-cell lung cancer (NSCLC) previously treated with platinum-based chemotherapy and anti-programmed death 1 or programmed death ligand 1 therapy.

First-in-Human Phase I/IB Dose-Finding Study of Adagrasib (MRTX849) in Patients With Advanced Solid Tumors (KRYSTAL-1).

Purpose: Adagrasib (MRTX849) is an oral, highly selective, small-molecule, covalent inhibitor of KRAS. We report results from a phase I/IB study of adagrasib in non-small-cell lung cancer, colorectal cancer, and other solid tumors harboring the mutation.

Materials And Methods: Patients with advanced -mutant solid tumors were treated with adagrasib 150 mg orally once daily, 300 mg once daily, 600 mg once daily, 1,200 mg once daily, or 600 mg orally twice a day using an accelerated titration design, which transitioned to a modified toxicity probability interval design when a predefined degree of toxicity was observed or target adagrasib exposure was achieved.

The incidence and predictors of new brain metastases in patients with non-small cell lung cancer following discontinuation of systemic therapy.

Objective: Patients with non-small cell lung cancer (NSCLC) metastatic to the brain are living longer. The risk of new brain metastases when these patients stop systemic therapy is unknown. The authors hypothesized that the risk of new brain metastases remains constant for as long as patients are off systemic therapy.

Hitting the Right Spot: Advances in the Treatment of NSCLC With Uncommon EGFR Mutations.

An understanding of the biology of uncommon epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) is evolving. These mutations are important for the selection of targeted therapy and the development of resistance. The advent of genomic profiling has led to guideline-recommended molecular testing to identify patients with NSCLC who carry uncommon EGFR mutations to aid in the selection of appropriate targeted therapy.

Presentation, Diagnosis and Management of Innominate Artery Thromboembolism.

Purpose: Acute thromboembolic disease of the innominate artery (IA) poses a unique set of therapeutic challenges, owing to its contribution to both the cerebral and upper extremity circulation, and risks of distal embolization via the carotid and subclavian arteries, respectively. Herein, we present a 74-year-old female who presents with acute IA thrombus treated successfully with right axillary and common carotid exposure and aspiration catheter-directed mechanical thrombectomy (CDT). Furthermore, an emerging use of CDT and its application in acute thromboembolism are outlined.

Amivantamab in EGFR Exon 20 Insertion-Mutated Non-Small-Cell Lung Cancer Progressing on Platinum Chemotherapy: Initial Results From the CHRYSALIS Phase I Study.

Purpose: Non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor () exon 20 insertion (Exon20ins) mutations exhibits inherent resistance to approved tyrosine kinase inhibitors. Amivantamab, an EGFR-MET bispecific antibody with immune cell-directing activity, binds to each receptor's extracellular domain, bypassing resistance at the tyrosine kinase inhibitor binding site.

Methods: CHRYSALIS is a phase I, open-label, dose-escalation, and dose-expansion study, which included a population with Exon20ins NSCLC.

The Common Thread: A Case of Synchronous Lung Cancers and a Germline CHEK2 Mutation.

Patients with one form of cancer are at increased risk for another, and this is true for lung cancer, where synchronous primary lung cancers are an increasing multifaceted challenge. Here, we present the case of a middle age woman who was found to have bilateral lung masses. Biopsy and subsequent testing revealed unique synchronous lung adenocarcinomas, each with unique genetic signatures.

Comprehensive Molecular and Clinicopathologic Analysis of 200 Pulmonary Invasive Mucinous Adenocarcinomas Identifies Distinct Characteristics of Molecular Subtypes.

Purpose: Invasive mucinous adenocarcinoma (IMA) is a unique subtype of lung adenocarcinoma, characterized genomically by frequent mutations or specific gene fusions, most commonly involving . Comprehensive analysis of a large series of IMAs using broad DNA- and RNA-sequencing methods is still lacking, and it remains unclear whether molecular subtypes of IMA differ clinicopathologically.

Experimental Design: A total of 200 IMAs were analyzed by 410-gene DNA next-generation sequencing (MSK-IMPACT; = 136) or hotspot 8-oncogene genotyping ( = 64).

Dynamic Management of Lung Cancer Care During Surging COVID-19.

Management of patients with lung cancer continues to be challenging during the COVID-19 pandemic, due to the increased risk of complications in this subset of patients. During the COVID-19 surge in New York City, New York University Langone Health adopted triage strategies to help with care for lung cancer patients, with good surgical outcomes and no transmission of COVID-19 to patients or healthcare workers. Here, we will review current recommendations regarding screening and management of lung cancer patients during both a non-surge phase and surge phase of COVID-19.

Tumour exosomal CEMIP protein promotes cancer cell colonization in brain metastasis.

The development of effective therapies against brain metastasis is currently hindered by limitations in our understanding of the molecular mechanisms driving it. Here we define the contributions of tumour-secreted exosomes to brain metastatic colonization and demonstrate that pre-conditioning the brain microenvironment with exosomes from brain metastatic cells enhances cancer cell outgrowth. Proteomic analysis identified cell migration-inducing and hyaluronan-binding protein (CEMIP) as elevated in exosomes from brain metastatic but not lung or bone metastatic cells.

Stage IV lung carcinoids: spectrum and evolution of proliferation rate, focusing on variants with elevated proliferation indices.

The spectrum and evolution of proliferation rates in stage IV lung carcinoids is poorly defined. In particular, there are limited data on the prevalence and characteristics of tumors exceeding the standard upper proliferative criteria-as defined largely based on early-stage carcinoids-in metastatic setting. Sixty-six patients with stage IV lung carcinoids were identified, and all evaluable samples (n = 132; mean 2 samples per patient) were analyzed for mitotic counts and Ki-67 rate.