Optimizing ALK-TKI Sequencing and Neurological Outcomes

For patients already on different first-line treatment, under what circumstances would you consider switching them to lorlatinib?

How should we approach CNS surveillance and management in 

Videos

Panelists discuss the circumstances under which they would consider switching patients on different first-line treatments to lorlatinib and outline approaches for CNS surveillance and management in ALK-positive patients.

Clinical Impact of ALK Inhibitor Data: Efficacy, Brain Metastases, and CNS Management Strategies

Dr Gadgeel: How do these data impact your treatment choice for your patients?

What specific patient factors would influence your decision between treatment options? What concerns might prevent you from choosing lorlatinib as a first-line treatment?

Panelists discuss how recent data influence treatment choices for ALK-positive NSCLC patients, highlighting specific patient factors that guide decisions and potential concerns regarding the use of lorlatinib as first-line therapy.

CROWN and BRIGHTSTAR Studies: Latest Data Insights

Dr Bestvina: Please discuss the key findings from the latest data for the CROWN/BRIGHTSTAR studies.

Please specifically discuss and emphasize efficacy end points here. How does the efficacy of this regimen compare with that of others in this space?

Panelists discuss the key findings from the latest data from the CROWN and BRIGHTSTAR studies, emphasizing efficacy end points and comparing the effectiveness of these regimens with that of others in the treatment landscape for ALK-positive NSCLC.

Molecular Testing and First-Line Treatment Selection in ALK-Positive NSCLC

Please provide an overview of the importance of molecular testing in NSCLC, particularly focusing on 

 testing evolved in recent years, and are there any emerging technologies or approaches that might impact your ability to identify 

What is your approach to first-line treatment selection for 

-positive disease in patients with NSCLC?

Panelists discuss the importance of molecular testing in NSCLC, particularly for ALK rearrangements, and explore how recent advancements and emerging technologies are shaping first-line treatment selection for ALK-positive patients.

Dr Bestvina on the Management of AEs Associated With Repotrectinib in ROS1+ NSCLC

Christine Bestvina, MD, thoracic oncologist, assistant professor of medicine, Section of Hematology/Oncology, Department of Medicine, University of Chicago Medicine, discusses strategies for managing adverse effects (AEs) associated with the ROS1 TKI repotrectinib (Augtyro) in patients with 

-positive metastatic non–small cell lung cancer (NSCLC).

 for patients with locally advanced or metastatic NSCLC harboring 

fusions on November 15, 2023. The approval was supported by findings from the phase 1/2 TRIDENT-1 trial (NCT03093116). In the phase 2 dose-expansion cohorts, patients with 

-positive NSCLC experienced high response rates regardless of whether they were TKI naive or TKI pretreated.

Regarding safety, 33% of patients in TRIDENT-1 experienced serious AEs. Treatment-related dose interruptions, reductions, and discontinuations caused by AEs were required by 48%, 35% and 8% of patients, respectively. The most frequent AEs to occur in at least 10% of patients included dizziness (all grade, 63%; grade 3 or 4, 1.9%), dysgeusia (48%; 0%), peripheral neuropathy (47%; 1.9%), ataxia (28%; 0.4%), cognitive disorders (23%; 0.8%), headache (19%; 0%), constipation (36%; 0%), nausea (19%; 0.4%), diarrhea (13%; 0.4%), vomiting (10%; 0.8%), dyspnea (30%; 7%), cough (14%; 0%), fatigue (24%; 1.1%), edema (12%; 0.8%), muscular weakness (21%; 1.5%), myalgia (12%; 0.4%), increased weight (14%; 1.9%), and vision disorders (11%; 0%). 

-positive disease with repotrectinib, it is important to be aware of the potential benefit of dose interruption, specifically in cases of dizziness, Bestvina begins. Instead of an immediate dose reduction, interrupting the dose according to the severity of dizziness may be a prudent initial approach, she states.

Additionally, Bestvina states that it is important to recognize that neuropathy associated with repotrectinib may manifest differently from conventional chemotherapy-induced neuropathy. Although distal extremity neuropathy is often observed, atypical presentations such as peri-oral neuropathy may also occur, which may be distinct from neuropathies commonly encountered in clinical practice. This highlights the importance of consistant monitoring for various neuropathic manifestations, Bestvina explains. 

Employing dose interruption and reduction as a tool for toxicity management is crucial for optimizing the drug's accessibility to patients while ensuring their well-being, Bestvina emphasizes. Understanding and navigating these nuances in repotrectinib's toxicity profile allows for informed treatment decisions, tailored strategies, and optimized outcomes for patients receiving repotrectinib, she concludes.

Christine Bestvina, MD, discusses strategies for managing adverse effects associated with the ROS1 TKI repotrectinib in patients with ROS1-positive metastatic non–small cell lung cancer.


Christine Bestvina, MD, assistant professor of medicine, Section of Hematology/Oncology, Department of Medicine, University of Chicago Medicine, discusses the emerging role of neoadjuvant chemoimmunotherapy in lung cancer.

In lung cancer, evaluating the efficacy of therapies utilized in later-line settings as earlier-line options is an important step to determine whether more patients can be cured, Bestvina says. To this end, perioperative immunotherapy has become an exciting potential treatment strategy for patients. 

The results of the phase 3 CheckMate 816 trial (NCT02998528) demonstrated a significantly improved pathological complete response rate with neoadjuvant chemotherapy plus nivolumab (Opdivo) vs chemotherapy alone in patients with resectable non–small cell lung cancer. During the 2021 ASCO Annual Meeting, additional findings showed that the neoadjuvant chemoimmunotherapy regimen did not impede feasibility and timing of surgery, limit the extent or completeness of resection, or increase surgical complications compared with chemotherapy alone in this patient population. 

As such, neoadjuvant chemoimmunotherapy will likely have a role in the treatment of patients with earlier-stage, resectable lung cancer, Bestvina concludes.

Christine Bestvina, MD, discusses the emerging role of neoadjuvant chemoimmunotherapy in lung cancer.  



Dr. Bestvina on the Emerging Role of Neoadjuvant Chemoimmunotherapy in Lung Cancer 

Christine Bestvina, MD, assistant professor of medicine, Section of Hematology/Oncology, Department of Medicine, University of Chicago Medicine, discusses challenges with interpreting molecular reports in lung cancer.

Several challenges in receiving and interpreting molecular reports exist in the lung cancer paradigm, Bestvina explains. For example, the available molecular profiling platforms present the data differently. Therefore, it may not always be clear which mutations are being tested for, how the data are recorded, and how the data are reported, Bestvina says. Additionally, it is unclear for some platforms whether targets, TKIs, and other available agents are being weighed for potential actionability in the context of identified aberrations. 

Moreover, as these molecular platforms are often based outside of an institution, the information generated is not always uploaded to electronic medical records (EMRs), which makes reporting the data in EMRs challenging for the clinician receiving the data, Bestvina concludes.

Christine Bestvina, MD, discusses challenges with interpreting molecular reports in lung cancer.  



Dr. Bestvina on Challenges With Interpreting Molecular Reports in Lung Cancer 

Christine Bestvina, MD, assistant professor medicine, Department of Medicine, Hematology/Oncology, University of Chicago Medicine, discusses the phase III KEYNOTE-407 trial in squamous non—small cell lung cancer (NSCLC).

In the KEYNOTE-407 trial, investigators reported prolonged profession-free survival and overall survival with the addition of pembrolizumab (Keytruda) to carboplatin plus paclitaxel or nab-paclitaxel (Abraxane) in newly diagnosed patients with metastatic squamous NSCLC.

Notably, all patients, regardless of PD-L1 status, derived benefit from the combination with manageable toxicity, concludes Bestvina. 

Christine Bestvina, MD, discusses the phase III KEYNOTE-407 trial in squamous non–small cell lung cancer.
 

Christine Bestvina, MD

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