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Updated ASCO Living Guidelines Highlight Need for Timely, Patient-Friendly Communication in Stage IV NSCLC

Fawzi F Abu Rous, MD, discusses updates to the ASCO Living Guidelines for the management of stage IV non–small cell lung cancer with driver alterations.

Fawzi F Abu Rous, MD

Fawzi F Abu Rous, MD

The ASCO Living Guidelines for stage IV non–small cell lung cancer (NSCLC) with driver alterations were updated in December 2024, making it more important than ever for oncologists to stay abreast of continually evolving treatment recommendations and effectively communicate these updates to patients, according to Fawzi F Abu Rous, MD.

He noted that a comprehensive, multidisciplinary understanding of treatment options ensures health care providers can invite patients to meaningfully participate in their own treatment planning.

The ASCO Living Guidelines provide real-time updates on the evolving oncology treatment paradigm, particularly regarding current standards of care (SOCs) for various cancers. In Version 2024.2 of the guidelines for stage IV NSCLC with driver alterations, the Expert Panel reviewed evidence from 4 studies and approved updated recommendations. These include offering osimertinib (Tagrisso) monotherapy, osimertinib in combination with platinum doublet chemotherapy, or amivantamab-vmjw (Rybrevant) plus lazertinib (Lazcluze) in the first-line setting, and offering platinum-based chemotherapy with or without amivantamab for patients without targetable mutations who progress on osimertinib or other EGFR TKIs in the second-line setting.

“For oncologists treating lung cancer, staying updated is essential, as the treatment paradigm is evolving rapidly,” Abu Rous stated in an interview with OncLive®. “It’s important to regularly consult the ASCO Living Guidelines, but also to review other key resources, such as the National Comprehensive Cancer Network guidelines and major data dissemination platforms. More importantly, oncologists must communicate these updates to patients in a way that facilitates informed decision-making.”

In the interview, Abu Rous, who is a thoracic medical oncologist at Henry Ford Health in Detroit, Michigan, expanded on the purpose and clinical utility of the ASCO Living Guidelines, detailed the evidence supporting updated treatment recommendations in the first- and second-line management of stage IV NSCLC with driver mutations, and highlighted investigational agents generating significant interest in the second-line NSCLC setting.

Abu Rous discussed ongoing research to address challenges in the management of squamous cell carcinoma of the lung in a concurrent article.

OncLive: What is the purpose of the ASCO Living Guidelines? Who serves on this panel?

Abu Rous: ASCO Living Guidelines is a committee created by ASCO with the goal of providing updates on the rapidly [evolving] landscape of oncology. ASCO has guidelines for each type of cancer. As a lung cancer expert, I serve on the Living Guidelines panel for stage IV NSCLC. There are also other panels responsible for providing updates on early-stage NSCLC and small cell lung cancer.

We try to divide and conquer because the field of lung cancer—thankfully, for our patients—is changing rapidly, and we are constantly working to improve outcomes. The goal of the Living Guidelines is to deliver real-time updates presented in a guideline format for oncologists, as well as for patients receiving the current SOC in lung cancer. This allows oncologists and other treating physicians to easily access relevant information and clinical insights to help inform treatment decisions.

[This panel encompasses] an inclusive group of lung cancer experts from both academic institutions and the community setting. We also include thoracic surgeons, especially for early-stage disease, as well as radiation oncologists who specialize in managing lung cancer. Importantly, we incorporate patient voices through the inclusion of patient advocates on each panel to ensure we are aligned with patient needs and perspectives. This is a multidisciplinary team that meets every few months—or even more frequently, as needed—to review new literature, assess whether there are any updates to the SOC, and incorporate necessary changes into the guidelines.

How have first-line treatment guidelines for patients with NSCLC harboring EGFR mutations evolved in recent years?

Thefirst-line treatment paradigm for patients with NSCLC harboring EGFR exon 19 deletions or L858R mutations has been a highly active area of research over the past year to year and a half. Historically, the first-line [SOC] was osimertinib monotherapy, which was FDA approved [in this setting] based on [data from] the [phase 3] FLAURA trial [NCT02296125].

More recently, we’ve seen updates from the [phase 3] FLAURA2 trial [NCT04035486], which evaluated the combination of osimertinib with chemotherapy. This combination regimen was subsequently approved by the FDA [for the treatment of patients with locally advanced or metastatic NSCLC harboring EGFR alterations].

We now have another first-line regimen consisting of amivantamab—a bispecific antibody—in combination with lazertinib—an oral EGFR TKI. Amivantamab is unique in that it has 2 binding sites: one that targets EGFR and another that targets MET—a relevant resistance pathway in EGFR-mutated NSCLC. Lazertinib, like osimertinib, inhibits the overactive EGFR protein. This combination was also recently approved by the FDA [for this indication].

Currently, we have 3 FDA-approved first-line regimens: osimertinib monotherapy, osimertinib plus chemotherapy, and amivantamab plus lazertinib. This is an exciting development for patients and oncologists, offering multiple options that can be selected based on individual clinical factors and through shared decision-making.

Additionally, in January 2025, a via press release reported that the combination of amivantamab and lazertinib in the [phase 3] MARIPOSA trial [NCT04487080] demonstrated an overall survival benefit compared with osimertinib monotherapy [in patients with previously untreated, locally advanced or metastatic NSCLC harboring EGFR mutations]. Although the full data have not yet been presented, we know that patients treated on the MARIPOSA study lived longer, and we are anticipating a full data presentation soon.

What are some of the updated second-line treatment recommendations for patietns with EGFR-mutated NSCLC?

In the second-line setting, amivantamab is FDA approved in combination with chemotherapy [for the treatment of patients with EGFR-mutated locally advanced or metastatic NSCLC] based on findings from the [phase 3] MARIPOSA-2 trial [NCT04988295]. This study enrolled patients with stage IV NSCLC harboring EGFR exon 19 deletions or L858R mutations who had progressed on first-line osimertinib. Patients were randomly assigned to receive either chemotherapy alone or chemotherapy plus amivantamab. The investigational arm achieved improved outcomes compared with chemotherapy alone, and the regimen was subsequently approved by the FDA for this indication.

Beyond currently approved therapies, several investigational agents are generating significant interest. One such agent is patritumab deruxtecan [HER3-DXd], an antibody-drug conjugate [ADC] that may soon be submitted for FDA approval. This agent leverages a HER3-directed monoclonal antibody conjugated to a cytotoxic payload, functioning as a targeted chemotherapy delivery system. The antibody selectively binds to HER3-expressing tumor cells, is internalized, and releases the chemotherapy intracellularly, potentially sparing healthy tissue. HER3-DXd has shown promising clinical activity in patients with EGFR-mutant NSCLC following progression on EGFR TKIs.

Additionally, amivantamab, which is already approved in combination with chemotherapy in the second-line setting in China, continues to be evaluated globally. The phase 3 PAPILLON trial [NCT04538664] compared chemotherapy plus amivantamab vs chemotherapy alone in [patients with EGFR exon 20 insertions]. Recently presented results demonstrated improved outcomes with the combination, further supporting the potential utility of amivantamab in post-osimertinib treatment strategies. This represents another promising approach under consideration for patients with EGFR-mutant NSCLC.

What are your key recommendations for colleagues seeking to incorporate these guideline updates into routine clinical practice?

Oncologists should actively examine and interpret new clinical data as these data become available. [Furthermore, a] shared decision-making approach requires the oncologist to stay current with emerging data and translate and contextualize those data in a patient-friendly manner. That enables patients to understand the rationale behind treatment recommendations and meaningfully participate in treatment planning.

For example, in the first-line setting for EGFR-mutant NSCLC, there are now 3 preferred and/or approved regimens. It is essential to clearly explain the pros and cons of each option, recommend the most appropriate regimen based on clinical expertise and data, and then elicit and incorporate the patients’ preferences and values into the final decision. This process reduces the burden on the patient to choose among multiple options and emphasizes the oncologist’s role in guiding the patient through complex treatment decisions.

Reference

Bazhenova L, Ismaila B, Abu Rous F, et al. Therapy for stage IV non–small cell lung cancer with driver alterations: ASCO Living Guideline, Version 2024.2. J Clin Oncol. 2024;42(36):e72-e86. doi:10.1200/JCO-24-02133


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