Estelamari Rodriguez, MD, MPH

Lung cancer increasingly hits never-smoking women; learn how biomarker testing, earlier screening, and stronger self-advocacy speed diagnosis and unlock better treatments.

The panel discusses the full multidisciplinary team required to optimize outcomes for patients with ROS1-positive advanced NSCLC: neuro-oncology for brain metastasis management, radiation oncology for CNS and bone disease, palliative care and symptom management specialists from diagnosis, physical therapy and nutrition, social work, and mental health services.

The panel addresses patients who received crizotinib or entrectinib in first line rather than lorlatinib, and who are now progressing.

The panel reinforces that oligo-progression management in ROS1-positive NSCLC requires careful distinction from strategies used in EGFR-mutated NSCLC.

For the patient with a G2032R resistance mutation and intracranial progression, the panel unanimously favors lorlatinib-based therapy in second line based on its known activity against solvent-front mutations and documented CNS penetrance, with median duration of response of approximately 7 to 8 months in this setting.

The second clinical case presents a patient with ROS1 fusion-positive advanced NSCLC who achieved partial response on frontline lorlatinib, maintained for 18 months, before symptomatic and radiographic progression: increasing primary tumor size, new contralateral pulmonary nodules, and brain MRI showing 3 new small intracranial lesions.

Given the patient's osseous disease, the panel discusses bone-directed therapy integration.

All panelists select lorlatinib at 600 mg for this patient based on response rates, duration of disease control, favorable tolerability, and its design intent to achieve superior CNS penetration compared to earlier-generation ROS1 inhibitors, which is particularly relevant given the patient's age, symptomatic disease burden, and risk of future CNS progression.

The first clinical case presents a 58-year-old female never-smoker with persistent cough, mild dyspnea, and new right-sided pleural effusion.

The panel addresses scenarios where patients arrive on treatments other than the panel's preferred agent.

Beyond efficacy, the panel identifies the key factors influencing agent selection: brain metastasis activity given the high prevalence of CNS involvement in younger ROS1-positive patients; toxicity profiles (earlier agents cause significant dizziness, taste changes, and neuropathic pain that are poorly tolerated chronically); frequency of clinic visits; and insurance access.

The panel discusses first-line treatment selection once a ROS1 fusion is confirmed in a treatment-naive patient.

The panel discusses how patients with ROS1-positive advanced NSCLC arrive in clinic through in-system diagnosis, second opinions, or new patient referrals and the detective work required to ensure complete molecular testing is available before treatment decisions.

ROS1 gene fusions occur in approximately 1% to 2% of advanced NSCLC cases, a small but clinically meaningful subset predominantly found in younger patients, women, light or never smokers, and those with non-squamous histology, most commonly adenocarcinoma.

ANK-101, an IL-12 anchored immunotherapy, is being studied with checkpoint blockade in patients with non–small cell lung cancer in a phase 1b trial.

With 4 ROS1-directed TKIs now in the mix, community oncologists need a clear framework for sequencing and CNS considerations in this rare NSCLC subset.

In closing, Dr. Rodriguez emphasizes that for patients who present with brain metastases, first-line treatment selection in EGFR-positive metastatic NSCLC requires weighing CNS efficacy, overall survival, tolerability, and the patient’s priorities, all framed as a shared decision-making conversation.

Dr. Rodriguez describes the current period in EGFR-positive lung cancer as one of active change in the first-line landscape: median overall survival in recent trials has lengthened compared with historical monotherapy data, and durations of CNS disease control are now reported in the range of years. She walks through how sequencing decisions are evolving.

Dr. Rodriguez turns to treatment burden, a central concern for Mr. Smith, who cannot drive because of seizure precautions, lives 45 minutes from clinic, and has a wife who works part-time. She describes the subcutaneous (SC) formulation of amivantamab and how it changes the administration schedule: dosing is approximately 5 minutes versus up to 4 to 5 hours for intravenous (IV) chemotherapy, and the maintenance interval moves from every 2 weeks to every 4 weeks (Q4W). Patients still come weekly during cycle 1, with maintenance visits less frequent thereafter.

Dr. Rodriguez addresses the wife’s concern about managing side effects at home. She frames the main toxicities of amivantamab in two categories. The first is infusion-related reactions (IRRs), which are reduced with the subcutaneous formulation. The second is the combination of cutaneous toxicity (rash, paronychia) and venous thromboembolism (VTE), which requires structured prophylaxis and a proactive plan for at-home management.

Dr. Rodriguez discusses CNS surveillance for Mr. Smith, who has selected subcutaneous (SC) amivantamab plus lazertinib for his 4 brain metastases. His wife asks how often he will need brain MRIs and what to watch for. Dr. Rodriguez contrasts current practice with the pre-targeted-therapy era, when she would have imaged at 6 to 8 weeks primarily to document response and offer radiation if a patient had not responded.

Dr. Rodriguez turns to overall survival (OS), the second question Mr. Smith and his wife raised. For MARIPOSA, median OS has not yet been reached for amivantamab plus lazertinib, with more than half of patients projected to be alive beyond 4 years based on the current data.

Dr. Rodriguez walks through the central nervous system (CNS) efficacy data for the three first-line options. She notes that MARIPOSA was specifically designed for close intracranial monitoring: patients with baseline brain metastases were imaged every 8 weeks, and patients without baseline brain metastases were also followed closely, which she cites as a reason for its National Comprehensive Cancer Network (NCCN) Category 1 recommendation.

Dr. Estelamari Rodriguez introduces the case of Mr. Smith, a 53-year-old man who presents with new-onset headaches and a witnessed seizure. He is a former light smoker (5 pack-year, quit 15 years ago) with type 2 diabetes and no hepatic, renal, or cardiac impairment, no history of venous thromboembolism (VTE), and an Eastern Cooperative Oncology Group (ECOG) performance status of 1.

Estelamari Rodriguez, MD, delivers her top takeaways from the 2026 IASLC Targeted Therapies in Lung Cancer meeting.

IASLC TTLC 2026 spotlights patient voices, ctDNA MRD, EGFR co-mutations, and ADCs—plus real-world gaps in testing and multidisciplinary lung care.

Experts weigh perioperative immunotherapy delays, rapid molecular testing, ctDNA MRD and emerging ADCs shaping early-stage lung cancer care.

TTLC 2026 spotlights next-gen lung cancer therapies, co-mutation strategies, and ctDNA monitoring—insights beyond CME for what’s coming next.

In this companion article, Dr. Estelamari Rodriguez reflects on the role of reactive and proactive treatment approaches for the management of chemotherapy-induced myelosuppression in small cell lung cancer.

In the fourth interview of the series, Dr. Estelamari Rodriguez from the University of Miami Health System considers unmet needs in extensive-stage small cell lung cancer and discusses the role of reactive and proactive approaches to the management of chemotherapy-induced myelosuppression.