Non-Small Cell Lung Cancer (NSCLC)

Adding adaptive radiation to chemotherapy may offer a novel approach to treating patients with advanced non–small cell lung cancer, according to Michael Steinberg, MD.

Results from the phase 2 KRYSTAL-1 trial led to the approval of adagrasib for patients with KRAS G12C–mutated non–small cell lung cancer by the European Commission.

Narjust Florez, MD, discusses the complexities of treating KRAS mutations in NSCLC, including the challenges of commutations affecting immunotherapy response, the need for prolonged progression-free survival with KRAS inhibitors, dosage considerations, and highlights ongoing unmet needs and future research directions.

Patients with non–small cell lung cancer who already received LN-145 in the phase 2 IOV-LUN-202 trial will be followed per trial protocol following the FDA’s clinical hold.

A review from the FDA confirms the dose comparison post-marketing requirement that was detailed at the time of sotorasib’s accelerated approval for those with KRAS G12C–mutated non–small cell lung cancer.

Narjust Florez, MD, emphasizes the importance of treating CNS metastases in KRAS G12C mutated NSCLC, highlighting the promising but limited data on adagrasib’s CNS penetrance and intracranial response, as shown in the KRystal-1b study, making it a preferred option for patients with CNS metastases despite its associated side effects.

Dr Narjust Florez discusses the higher incidence of hepatotoxicity with sotorasib as shown in real-world data, and suggests adagrasib as a preferable option for patients with pre-existing liver dysfunction or inflammation, highlighting the need to consider patient history and liver function when choosing KRAS inhibitors.

The application for amivantamab and lazertinib for locally advanced or metastatic non–small cell lung cancer is supported by data from the phase 3 MARIPOSA trial.

“KRAS is probably the most exciting area in clinical trials right now, not only in thoracic oncology but also pancreatic and colorectal cancer, where we’ve seen a lot of combination therapies. My view is the small molecule inhibitors are the base, not the ceiling.”

During the 2023 European Society of Medical Oncology, experts in the field of lung cancer convened to discuss the use of biomarker testing and updated trial results that were presented.

Dr Narjust Florez discusses the hepatoxicity associated with KRAS G12C inhibitors, noting both adagrasib and sotorasib pose liver damage risks, but real-world data suggests adagrasib may have a lower risk; she emphases the importance of considering other causes of hepatoxicity before attributing it solely to these therapies.

CodeBreaK 100 compares the safety and efficacy of pembrolizumab combined with adagrasib or sotorasib in treating KRAS G12C NSCLC, noting sotorasib has a longer presence and familiarity in clinical use.

Alykhan Nagji, MD, provides a brief overview of the landscape surrounding the treatment of patients with stage-III resectable NSCLC.

Data from a real-world study may help clinicians in treatment decision-making for those with extensive-stage small cell lung cancer who are unable to afford PD-L1 inhibitors.

Adding camrelizumab to chemotherapy appears tolerable for patients with resectable stage IIIA or IIIB non–small cell lung cancer in the phase 2 TD-FOREKNOW trial.

KRYSTAL-7 is a study exploring the efficacy of adding adagrasib to first-line pembrolizumab in patient with NSCLC with varying PD-L1 expression levels, showing promising response rates and progression-free survival, but also adverse events like hepatotoxicity.

Dr Narjust Florez discusses the KRYSTAL-1 trial, focusing on the effectiveness and side effects of adagrasib in treating patients with NSCLC and KRASG12C mutations, and noting their impact on progression-free and overall survival.

The panelists close their discussion on non-small cell lung cancer by emphasizing the need for continued research, early screening, and collaboration with dermatologists to address the unmet needs and improve overall outcomes.

Treatment with visugromab plus nivolumab in patients with relapsed/refractory solid tumors in the phase 2a GDFATHER-2 trial appears to exhibit safety and tolerability.

Dr Narjust Florez outlines FDA-approved firstline therapy options for KRAS G12C mutated non-small cell lung cancer, and notes most patients progress and require second line targeted therapy.

Narjust Florez, MD, discusses KRAS G12C mutated non-small cell lung cancer, a subset of KRAS mutations which comprises 14% of NSCLC cases.

Alexander I. Spira, MD, PhD, and Joshua K. Sabari, MD, conclude their discussion with key takeaways on the evolving treatment of patients with NRG1 fusion–positive malignancies.

The expert panel discusses NRG1 fusions in pancreatic cancer and the potential role of zenocutuzumab as a therapeutic option.

Alexander I. Spira, MD, PhD, and Joshua K. Sabari, MD, discuss ongoing clinical trials focused on NRG1-targeted therapies.

Clinical insights on the diagnosis of NRG1 fusions in patients with non–small cell lung cancer.