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We're now going to continue with talking about preparing patients and their care partners for ALK inhibitor therapy. This is the patient perspective. Patients come into these appointments with all kinds of questions on their minds. Here are just some examples. I'm worried about my diagnosis. Is there a cure? I'm worried about the treatment. Will there be side effects? I don't want to lose my job and my independence. We will begin our session by looking at a typical patient who you may see in your office. We will refer back to Maria on a number of occasions during the session to ensure our learning is focused on supporting patient outcomes. Let's meet Maria. She's a 57 year old Latina female. She is newly diagnosed with metastatic fusion positive adenocarcinoma. She has a solitary liver metastasis and multiple bilateral lung nodules. Her ECOG performance status is one. Some of her key comorbidities are hypertension for which she is on lisinopril, type 2 diabetes for which she is on metformin, and baseline peripheral neuropathy from prior taxane chemotherapy. She also has chronic dry eye. Her baseline workup included an EKG with a QTC interval of 420 milliseconds, LFTs that were within normal limits, a baseline ophthalmologic examination, and a brain MRI. In terms of her social situation, she lives with her husband, who is her primary caregiver. She speaks some English, but primarily speaks Spanish. She works part-time as a cashier, and she has an adult daughter who lives nearby. She does not have access to a reliable vehicle and has limited internet access at her home. Here's our first polling question. Before initiating treatment for Maria, which single item is most critical for the patient and care partner to understand and be able to act on immediately? A, how to manage mild nausea at home. B. Expected timeline for tumor response. C, the fasting lipid testing will be done at 3 months, and D, who to contact and which symptoms require immediate reporting. All right. Thank you all for your responses. We have an update from Maria. She reports after 4 weeks on treatment that she is experiencing increased mental fog, intermittent dizziness, and slower task completions at work. Her husband notes that he needs to remind her to take her medication. Her lab tests show that her LFTs have risen to about twice the upper limit of normal. She gets another brain MRI which is unchanged. She is triaged by the nurse and scheduled with the oncologist for assessment. Polling question, which single clinical finding in marine studies most strongly warrants immediate evaluation and consideration of treatment adjustment? A. Mild intermittent dizziness without focal deficits. B, AST ALT elevation to about twice the upper limit of normal with no abdominal pain or jaundice. C. New or worsening confusion and change in behavior reported by Care Partner. D. slower task completion at work, but no other neurologic complaints. Thank you for your responses. We've arrived at another polling question. Maria's husband reports that she forgot where she was for several minutes and seems unusually drowsy today. What is the most appropriate immediate clinical action? A, Schedule a routine clinic visit for one week for assessment. B. Advise caregiver to monitor at home and call back if there's worsening. C. Recommend increasing fluid intake and rest, continue therapy. D, instruct caregiver to bring the patient to VED or urgent clinic for evaluation now and consider holding treatment. Thank you for your responses. So for a patient update, week 12 on treatment, the patient, uh, dosing routine is established with reminders from her husband when needed. He reports intermittent mental fog, mild neuropathy, occasional nausea, controlled with Niemetics when necessary. And then recent data showed LFTs peaked and then down trended after temporary treatment hold. No new focal logic, no new focal neurologic signs. Transportation and limited internet access do remain barriers to remote reporting. The clinical implication is that the patient is engaged but needs clear, low-tech reporting pathways, explicit escalation thresholds, and defined team roles for rapid responses. A polling question Who should be the first clinical contact for Maria if her husband reports sudden new confusion? Is it A the primary care physician, B, the oncologist, C, nurse triage, D, pharmacist, or E, social worker? All right. Well, thank you for your responses, everybody. The correct answer here would be going through the nurse triage. Patient update, 6 months on treatment. There's been a partial response on 3rd generation AK inhibitor, improved energy, and persistent mild neuropathy. Values remain, preserve cognition, maintain part-time work, and avoid hospitalization. The attitude to risk today is willing to accept temporary hold or reduction to preserve cognitive function and outpatient care. Now this could shift if disease progresses, toxicities accumulate, or if caregiver burden increases. The clinical implication here is to document current preferences and review at each major decision node, toxicity, progression, or major life changes. From a clinician perspective, we want to capture the current landscape of ALKC positive lung cancer. We know that ALK gene fusions drive oncogenesis in a subset of non-small cell lung cancer. We also know that we have selective ALK inhibitors that produce high objective response rates, long progression-free survival, and improved CNS control, particularly as compared to chemotherapy. International guidelines recommend ALEC-DKI as a standard first line therapy for ALEC positive advanced non-small cell lung cancer. CNS penetration and intracranial response are critical differentiators among agents and drive selection when brain metastases or cognitive preservation are priorities. Amongst the OCTKIs we see different toxicity profiles, so we have to balance efficacy, CNS activity, and patient priorities, as well as drug-drug interactions. Before we discuss any specific treatment options with our patient, we should clarify the goals of treatment. Are we treating to cure this patient? Are we treating to prolong their survival? Are we treating to improve their quality of life so that the patient understands the likely outcomes and can conceptualize the treatment within their goals of care. Sometimes these things are not mutually exclusive. We obviously, you know, want to improve quality of life whether we're curing a patient or prolonging their survival. But we do want to take all these things into account. So in this case we have a shared discussion with our patient Maria. She wants to prioritize maintaining cognition and independence while continuing to work part time. She does not want to spend time in the hospital. In light of all of this, we're going to recommend treatment with a 3rd generation ALC inhibitor, uh, specifically lorlatinib, which has A high objective response rate, long progression-free survival, and excellent CNS control. Since this patient would like us, would like to prioritize maintaining her cognition, we do have to be cognizant of the neurocognitive side effects of lolotinib, which we'll discuss in more detail later. Um, I will frequently start these patients on A lower dose of the drug. The label dose is 100 mg, but excellent efficacy has been observed with the 50 and 75 mg doses, and we do see significantly lower rates of toxicity. So especially in a, in a patient who has already has some concerns around cognition, I think certainly starting at a lower dose can be a good middle ground strategy. Important information to, to talk to Maria about here are the most likely AEs and when to expect their onset. So I would talk about neurocognitive side effects, hyperlipidemia. Hepatic enzyme changes and peripheral neuropathy, but also mentioned peripheral edema, which we do see across all of the ACTKIs. It's also important to discuss which of these. symptoms and side effects to worry about urgently versus non-urgently. Obviously, with significant neurocognitive changes and seizures, those are um Very challenging and, and dangerous, and we want people to, to let us know about those right away. Um, we also wanna, you know, check their labs and, and be on top of any sort of evidence of liver injury. It's also important to discuss what kind of monitoring patients can expect to have, both in terms of labs, EKG monitoring, and other specialist examinations. And then it's always important to review all of the other medications and drugs that a patient is taking, both prescription.