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CURE® spoke with a lung cancer treatment expert about study findings showing survival benefits with the addition of radiotherapy to TKI treatment.
A lung cancer treatment expert discusses study findings in non–small cell lung cancer.
EGFR-tyrosine kinase inhibitor (EGFR-TKI) treatment given with concurrent thoracic radiotherapy (TRT) treatment was shown to improve progression-free survival (PFS) in patients with EGFR-mutated oligo-organ metastatic non–small cell lung cancer (NSCLC), with acceptable and tolerable treatment-related adverse effects, according to phase 3 trial data.
Researchers published findings from their multicenter phase 3 clinical trial in the Journal of Clinical Oncology, which enrolled 118 patients in China between April 14, 2016, and Feb. 25, 2022.
The median PFS was 10.6 months among patients treated with EGFR-TKIs versus 17.1 months for patients treated with EGFR-TKIs and TRT. The median overall survival (OS) was 26.2 months and 34.4 months, respectively, in these treatment groups. Rates of treatment-related adverse effects were 5.1% and 11.9%, respectively.
CURE® spoke with Dr. Coral Olazagasti, an assistant professor at the Sylvester Cancer Center, University of Miami and a member of the CURE® advisory board, about this study and its findings via email.
Olazagasti: The key takeaway for patients with EGFR-mutated advanced NSCLC is that [treatment with] concurrent lung radiation therapy and TKIs leads to longer survival benefits compared with TKIs alone, particularly in those with oligo-organ metastatic disease [where the cancer has spread to a limited number of organs]. This approach leverages the synergy between targeted therapy and localized radiation to manage metastases more effectively, potentially improving overall outcomes. It's an important consideration for personalizing treatment plans in this patient population.
Tyrosine kinase inhibitors: A type of targeted therapy designed to stop cancer cells from growing.
Thoracic radiotherapy: Treatment using high-energy radiation in the chest, lungs and surrounding region.
Progression-free survival (PFS): The time a patient lives without their disease spreading or worsening
Overall survival (OS): The time a patient lives, regardless of disease status.
The study's findings of enhanced efficacy in combining TKIs with radiation therapy, particularly among women, older patients, and those with brain metastases, are intriguing. These observations suggest that certain patient subgroups may derive greater benefit from combined modality treatments, highlighting the need for personalized therapeutic approaches.
However, the referenced study utilized [Conmana (icotinib)], a first-generation TKI. However, current standard care in the United States has shifted towards third-generation TKIs, such as [Tagrisso (osimertinib)], due to superior efficacy. Notably, [Tagrisso] has demonstrated a median OS of 38.6 months in patients with EGFRexon 19 deletions or exon 21 L858R mutations, surpassing the 26.2 months observed with [Conmana]. This significant difference underscores the importance of evaluating the applicability of older regimens in today's clinical practice. The potential benefits of combining radiation therapy with TKIs warrant further investigation, especially concerning modern TKIs like [Tagrisso]. Assessing the role of consolidation radiation therapy alongside current standard-of-care TKIs could provide valuable insights into optimizing treatment strategies for patients with oligo-organ metastatic disease.
Recent developments, such as the approval of the combination of [Rybrevant (amivantamab)] with [Lacluze (Lazertinib)] as a first-line therapy for EGFR-positive advanced NSCLC, have shown promising results. The MARIPOSA trial reported a 7.1-month PFS benefit over [Tagrisso], indicating a potential shift in first-line treatment approaches.
In the referenced study, oligo-organ metastasis was defined as the presence of metastatic disease in three or fewer synchronous organs in patients with advanced NSCLC. This categorization focuses on patients with a limited burden of metastatic disease, which may be more amenable to aggressive local and systemic therapies, such as the combination of radiation and TKIs.
The findings of this study raise important considerations when evaluating their applicability to broader populations, particularly in regions outside of China, where the study was conducted. Differences in patient demographics, genetic variations and healthcare systems can significantly impact the generalizability of the results.
The baseline characteristics of the study population also highlight potential biases that may have influenced the results. The average age of participants was less than 60 years, which is younger than the typical NSCLC population in many Western countries, where patients are often older and may have additional comorbidities. Furthermore, the combination therapy arm predominantly included patients with a lower metastatic burden (one or fewer metastatic organs) compared to the TKI-alone group, where most patients had involvement in two organs. This imbalance could have favored the combination therapy arm, raising questions about whether similar benefits would be observed in a population with a higher metastatic burden or more advanced disease.
Another important consideration is the higher incidence of grade 3 [severe] or 4 [life-threatening] treatment-related adverse events in the combination therapy arm [11.9% versus 5.1% in the TKI-alone group]. While the combination therapy showed promising efficacy, the increased toxicity could limit its applicability to older or comorbid patients who may not tolerate such aggressive treatment regimens. The toxicity profile is a critical factor in determining the feasibility of incorporating combination therapy into standard practice. Additionally, the study’s use of [Conmana], a first-generation TKI, as the treatment backbone limits its relevance in the context of modern care.
To ensure applicability to a broader and more diverse patient population, future trials should include patients of varying ages, comorbidities, ethnicities and metastatic burdens. Subgroup analyses focusing on these factors, along with careful monitoring of toxicity, are crucial to determine which patients are most likely to benefit from combination therapy. Such studies will provide clearer insights into the feasibility and potential benefits of integrating radiation therapy with modern TKIs in contemporary clinical practice.
Reference: “Thoracic Radiotherapy Improves the Survival in Patients With EGFR-Mutated Oligo-Organ Metastatic Non–Small Cell Lung Cancer Treated With Epidermal Growth Factor Receptor–Tyrosine Kinase Inhibitors: A Multicenter, Randomized, Controlled, Phase III Trial” by Dr. Hongfu Sun, Journal of Clinical Oncology.
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