medwireNews: People with EGFR-positive non-small-cell lung cancer (NSCLC) may benefit from individualized risk-profiling, say researchers who observed a high recurrence risk following resection but also identified a subgroup that may be cured without adjuvant osimertinib.
The cohort study, by Daniel Tan (National Cancer Centre Singapore) and colleagues, included 723 patients diagnosed with stage IA to IIIA NSCLC between 2010 and 2018 who underwent surgery with curative intent with or without adjuvant radiation and/or platinum doublet chemotherapy.
The research therefore predates the landmark ADAURA trial, which led to approvals by the US FDA approval and the EMA for adjuvant osimertinib for resectable stage IB–IIIA NSCLC, the investigators explain.
However, in a comment accompanying the JAMA Network Open publication, Christopher D’Avella (University of Pennsylvania, Philadelphia, USA) and J Nicholas Bodor (Fox Chase Cancer Center, Philadelphia) say that there is still debate surrounding which patients benefit most from adjuvant osimertinib.
“Many oncologists admit a greater enthusiasm for offering this additional therapy to patients with stage II to IIIA disease and acknowledge the need for more nuanced discussions regarding the risks and benefits in stage I disease,” they write.
D’Avella and Bodor believe the current study findings “highlight that stage of disease is only a part of this equation and support the need for further research on individual risk profiling and prognostic modeling for recurrence.”
Tan et al report that, in their cohort, the 2-year disease-free survival (DFS) rate following resection was 70.2% among the 389 patients with EGFR-positive NSCLC and 67.6% in the 334 participants with wildtype EGFR, a nonsignificant difference.
There was also no significant difference between the two groups in 5-year DFS (50.3 vs 50.0%), but overall survival rates at both 2 years (95.5 vs 88.0%) and 5 years (77.7 vs 66.6%) were significantly higher in in the EGFR-positive versus wild-type NSCLC groups.
Among the patients with EGFR-positive NSCLC, 2-year DFS was 81.0% for individuals with stage IA disease, 78.4% for stage IB, 57.1% for stage II, and 46.6% for stage IIIA.
Of note, 37.2% of all participants with stage IB to IIIA disease were alive and disease-free at 5 years, which “is a relevant concern in light of ADAURA” when considering that people with stage IA and stage IB EGFR-positive NSCLC had a similar recurrence risk, the researchers remark.
They say: “This highlights the importance of mature data and the need to individualize recurrence risk profiles.”
To address this, Tan and co-investigators performed genomic and transcriptomic profiling for a subgroup of 86 patients with EGFR-positive NSCLC and integrated the data with histopathologic information to develop a prognostic model for recurrence.
They identified micropapillary subtype, and alterations in CTNBB1 and RNHP1 as characteristics associated with increased recurrence risk, whereas RB1 copy number loss was associated with decreased risk.
The authors believe that their model could “help to select patients with stage IB NSCLC who would benefit from adjuvant osimertinib and prospectively identify patients with high-risk stage IA NSCLC for enrolment in adjuvant clinical trials.”
They conclude: “Further studies are needed to elucidate individualized surveillance and adjuvant treatment strategies for early-stage EGFR-positive NSCLC.”
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JAMA Netw Open 2021; 4: e2131892
JAMA Netw Open 2021; 4: e2132860