Misako Nagasaka, MD, PhD

Treatment with lorlatinib might be effective regardless of the presence of central nervous system metastases, according to Misako Nagasaka, MD, PhD.

Most central nervous system events with lorlatinib were grade 1 or 2 in the phase 3 CROWN trial.

Treatment with lorlatinib did not increase cardiovascular events among patients with ALK-positive non–small cell lung cancer in the CROWN trial.

At 5 years, 60% of patients who received lorlatinib in the phase 3 CROWN study achieved progression-free survival.

Panelist discusses how HER2-directed tumor-agnostic treatments are likely to see expanded applications across multiple cancer types, driven by improved biomarker testing and emerging clinical evidence. This approach may become increasingly personalized through enhanced molecular profiling, potentially leading to more precise patient selection and combination strategies.

Panelist discusses how the DESTINY-PanTumor02 study enrolled 267 patients with different tumor types, including endometrial, cervical, ovarian, bladder, biliary tract, and pancreatic cancer.

Panelist discusses how HER2-directed tumor-agnostic therapies represent an emerging treatment paradigm focused on targeting HER2 mutations regardless of cancer type. Current agents such as trastuzumab deruxtecan show promise across multiple tumor types that express HER2, moving beyond traditional cancer-specific approaches. This precision medicine strategy may expand treatment options and improve outcomes for patients with HER2-altered cancers who previously had limited therapeutic choices.

Panelist discusses how the DESTINY-Lung02 trial was a dose optimization study where patients with HER2-mutated non–small cell lung cancer (NSCLC) were randomly assigned to a starting dose of 5.4 mg/kg vs 6.4 mg/kg of trastuzumab deruxtecan (T-DXd). DESTINY-Lung03 was a frontline study for HER2 overexpression in NSCLC looking at different combinations of treatment with T-DXd and immunotherapy agents with or without chemotherapy.

Panelist discusses how HER2 testing evaluates protein overexpression, gene amplification, and mutations. Although breast and gastric cancers typically show overexpression/amplification, other tumors more commonly harbor mutations.

Introduction to HER2-Directed Tumor-Agnostic Approaches

Panelists discuss key takeaways from the analysis and offer clinical pearls on incorporating prophylactic dexamethasone 8 mg into treatment with amivantamab and lazertinib for community colleagues.

Panelists discuss other adverse events associated with amivantamab and lazertinib beyond infusion-related reactions.

Panelists discuss the clinical implications of the SKIPPirr trial data presented at the 2024 World Congress on Lung Cancer, including whether it might reduce resistance to using this combination in practice, how to implement supportive measures such as prophylactic dexamethasone 8 mg, potential barriers to implementation, strategies to overcome these barriers, and ways to educate patients about infusion-related reactions and the benefits of prophylactic measures.

Panelists discuss the frequency, timing, and symptoms of infusion-related reactions with amivantamab plus lazertinib, how these drugs compare with other treatments such as datopotamab deruxtecan (DXd) or patritumab DXd (HER3-DXd), and the management strategies and prophylactic measures used, especially for patients with EGFR exon 19 or L858R advanced/metastatic non–small cell lung cancer who have experienced progression on prior therapies.

Panelists discuss how amivantamab, FDA approved for first-line treatment of advanced non–small cell lung cancer with specific EGFR mutations, can lead to significant infusion-related reactions, including serious cases that may require dose adjustments or discontinuation.

Misako Nagasaka, MD, PhD, discussed the approval of amivantamab plus chemotherapy for patients with EGFR exon 20 insertion mutations non–small cell lung cancer.

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.

Dr Sai-Hong Ou discusses the future of treatment for non-small cell lung cancer with EGFR exon 20 insertion mutations, highlighting the complexity of these mutations and the need for precision treatments.

Drs Misako Nagasaka, Sai-Hong Ou, Janellen Smith discuss the management of adverse events, such as infusion reactions and rash, associated with amivantamab treatment for patients with EGFR exon 20 insertion mutations.

Sai-Hong Ou, MD, PhD, and Janellen Smith, MD, discuss the management of a patient with non-small cell lung cancer and an EGFR exon 20 insertion mutation who experienced a rash while on treatment with amivantamab; they highlight the importance of continuous treatment and potential considerations for this patient group.

Sai-Hong Ou, MD, PhD, discusses the challenging management of patients EGFR-mutant non-small cell lung cancer who develop resistance to EGFR tyrosine kinase inhibitors, emphasizing the importance of understanding the resistance mechanism to tailor treatment.

Drs Janellen Smith and Misako Nagasaka discuss dermatological adverse events in patients with non-small cell lung cancer associated with EGFR tyrosine kinase inhibitors, offering advice on prevention, treatment, and when to involve a dermatologist.

Dr Sai-Hong Ou and Dr Misako Nagasaka discuss the treatment strategies for EGFR-mutant non-small cell lung cancer, emphasizing the importance of individualized decision making and a multidisciplinary approach.

Next steps for research in lung cancer may include identifying how the gut microbiome impacts responses and adverse effects associated with treatment, says Misako Nagasaka, MD, PhD.

Sai-Hong Ou, MD, PhD, discusses the rapidly evolving landscape of first-line therapy for sensitizing EGFR mutant non-small cell lung cancer, including potential combination therapies and the introduction of new treatment options, such as antibody drug conjugates.

Dr Sai-Hong Ou and Dr Janellen Smith discuss the case of a 59-year-old patient with non-small cell lung cancer and an EGFR mutation who experienced severe diarrhea and acne form rash while on osimertinib, providing insights into managing these treatment-related side effects.

Dr Sai-Hong Ou highlights the significance of next-generation sequencing for detecting EGFR mutations in patients with non-small cell lung cancer and the potential for adjuvant testing regardless of disease stage.

In this program, Sai-Hong Ou, MD, PhD, discusses biomarker testing for precision medicine in non-small cell lung cancer, emphasizing the importance of both tissue and blood-based genotyping, and the need for a complementary approach due to potential limitations in detecting targetable mutations.

Misako Nagasaka, MD, PhD, and Kristen Neumann, DNP, FNP-C, emphasize the importance of patient education, discussing how understanding the biological reasons behind treatments for EGFR-mutated non-small cell lung cancer and their side effects can lead to better outcomes, and highlighting the need for collaborative care and clear communication.

Misako Nagasaka, MD, PhD, and Kristen Neumann, DNP, FNP-C, discuss the importance of early dermatological consultations and multidisciplinary education for managing infusion-related adverse events like rashes from amivantamab, emphasizing the benefits of a well-coordinated team and the value of experience in responding to reactions.