Proceedings of the 1st biannual bridging the gaps in lung cancer conference.

Lung cancer is the leading cause of cancer death in the US and globally. The mortality from lung cancer has been declining, due to a reduction in incidence and advances in treatment. Although recent success in developing targeted and immunotherapies for lung cancer has benefitted patients, it has also expanded the complexity of potential treatment options for health care providers.

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.

Combinatorial therapy is a safe and durable treatment option in -rearranged non-small cell lung cancer with an acquired exon 14 skipping mutation mediated resistance to alectinib: a case report.

Background: Anaplastic lymphoma kinase () tyrosine kinase inhibitors (TKIs) are standard first line treatment for rearranged non-small cell lung cancer (NSCLC) and have demonstrated high and durable response rates. Despite these initial responses, patients eventually develop resistance through dependent and independent alterations. These resistance mechanisms have made treatment decisions increasingly more complex.

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.

Matching-adjusted indirect comparison of amivantamab vs mobocertinib in platinum-pretreated Exon 20 insertion-mutated non-small-cell lung cancer.

We assessed relative efficacy and safety of amivantamab versus mobocertinib in patients with non-small-cell lung cancer with exon 20 insertion (exon20ins) mutations who progressed on prior platinum-based chemotherapy. This matching-adjusted indirect comparison used patient-level data from CHRYSALIS (NCT02609776) and aggregate data from a mobocertinib trial (NCT02716116) to match populations on all clinically relevant confounders. While both agents had similar efficacy for time-to-event outcomes, objective response rate was significantly higher for amivantamab.

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.

Amivantamab, an Epidermal Growth Factor Receptor (EGFR) and Mesenchymal-epithelial Transition Factor (MET) Bispecific Antibody, Designed to Enable Multiple Mechanisms of Action and Broad Clinical Applications.

Substantial therapeutic advancements have been made in identifying and treating activating mutations in advanced non-small cell lung cancer (NSCLC); however, resistance to epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition factor (MET) inhibitors remains common with current targeted therapies. Amivantamab, a fully human bispecific antibody targeting EGFR and MET, is approved in the United States and other countries for the treatment of patients with advanced NSCLC with EGFR exon 20 insertion mutations, for whom disease has progressed on or after platinum-based chemotherapy. Preliminary efficacy and safety have also been demonstrated in patients with common EGFR- or MET-mutated NSCLC.

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.