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In Hollywood, the word "mutant" generally has a negative connotation, with movie plot lines that involve . But in the lung cancer space, harboring an EGFR mutation may confer an advantage.

In a study that sought to pinpoint survival outcomes for patients with synchronous oligometastatic non-small-cell lung cancer (NSCLC) who got local consolidative therapy (LCT), "EGFR mutations were associated with longer OS [overall survival] among oligometastatic patients treated with comprehensive LCT in addition to systemic therapy," reported Saumil J. Gandhi, MD, PhD, of the University of Texas MD Anderson Cancer Center (MDACC) in Houston, and colleagues.

They identified patients at MDACC who presented between 2000 and 2017 with stage IV NSCLC and ≤3 synchronous metastatic sites, and then grouped them according to mutational statuses, with almost a fourth harboring EGFR mutations.

Gandhi's group reported in that, on multivariable analysis, patients with EGFR mutations had lower mortality risk versus wild-type patients, and that among patients with known EGFR mutational status who received comprehensive LCT, EGFR mutations were linked with lower mortality, again compared with wild-type patients.

"[W]e find through this analysis that patients with EGFR mutations receiving both TKIs [tyrosine kinase inhibitors] and comprehensive LCT had the most favorable outcomes, with a median survival of 98 months, which is longer than that observed for any other mutational subset, and remarkably high, considering these patients all presented with stage IV disease at diagnosis," the researchers stated.

The study patients underwent a radiotherapy (RT) protocol per a by Gandhi and colleagues, and two experts highlighted the role of RT in the LCT setting for EGFR-mutated, and/or oligometastatic NSCLC.

Is postoperative RT (PORT) an option in patients with EGFR-mutated NSCLC?

Florence "Katie" Keane, MD, Massachusetts General Hospital, Boston: I do not recommend PORT in patients who have one involved lymph node station, patients with EGFR mutations, or patients with high PD-L1 expression. I have considered and continue to consider PORT in patients who have low PD-L1 expression ... multiple involved lymph node stations, and/or extranodal extension. And when delivering PORT, use of VMAT [volumetric-modulated arc therapy] and IMRT [intensity-modulated RT], and avoiding elective nodal radiation, is very important (2022 American Society for Radiation Oncology [ASTRO] meeting).

What are some unanswered questions for RT in oligometastatic NSCLC?

Puneeth Iyengar, MD, PhD, UT Southwestern Medical Center, Dallas: Historically, we've defined a patient as having limited number of metastatic sites of disease, or oligometastatic, as three or fewer lesions of spread. The reason we chose that number is because we want to identify subsets of NSCLC patients who may benefit from local treatment.

But that's ... a number kind of pulled out of the air. What we need to do is develop better predictive and prognostic models of understanding which patients truly have oligometastatic disease, versus those patients who are going to develop widely metastatic disease, in the hopes that we can identify the most optimal patients that will benefit from our local treatment approaches. So that is a really outstanding question in the field.

Second question is sequencing and timing -- when should we add this RT? Should we add this RT for oligometastatic NSCLC patients at their time of diagnosis? Should we treat metastases only at the time of consolidation or after they've gotten three or four courses of systemic therapy? Or should we include this treatment only when they progress, and then only if they have oligoprogression?

Then there's some other, traditional, intrinsic questions, such as what is the optimal RT dose? What is the optimal number of treatments that we need to employ in order to facilitate optimal tumor control? At the end of the day, it's a synergy between systemic therapy and it's a synergy with its effect on local therapy and vice versa, so we want to make sure that what we're doing has the appropriate synergy between local and systemic therapies. So I think those are three fundamental questions that remained unanswered. (.)

No doubt answers to some of those questions can be found in the 2023 ASTRO/European Society for Radiotherapy and Oncology (ESTRO) authored by Iyengar and colleagues. Topics covered include patient selection, treatment planning, and delivery techniques for definitive LCT.

What are some upcoming noteworthy trials in this patient population?

Rolf Stahel, MD, European Thoracic Oncology Platform (ETOP) International Breast Cancer Study Group (IBCSG) Partners Foundation, Berne, Switzerland: We have a very exciting year in ETOP... we have trials in the space of EGFR-mutated NSCLC, one for patients with oligometastatic disease where we check whether upfront radical treatment ... RT in addition to osimertinib [Tagrisso] will have a benefit for survival []. We have also a trial [] for patients who failed EGFR treatment, which will be a combination of amivantamab [Rybrevant], lazertinib [Leclaza], and bevacizumab ().

Read the study here.