Effects of EGFR driver mutations on pathologic regression in resectable locally advanced non-small cell lung cancer treated with neoadjuvant chemoradiation and completion surgery.

Abstract

OBJECTIVE:

We hypothesized that driver mutations in epidermal growth factor receptor (EGFR) are associated with decreased pathologic response to neoadjuvant chemoradiation (NA-ChRT) in locally advanced non-small cell lung cancer (LA-NSCLC).

METHODS:

Patients with Stage IIB-IIIA NSCLC treated with NA-ChRT, completion surgery, and underwent molecular profile testing were identified in a lung cancer database. Pathologic response was quantified using: (i) major pathologic response (MPR), (ii) complete pathologic response (pCR), and (iii) mean residual viable tumor cells (MRTC). Two groups were formed based on the presence or absence of driver mutations. Clinical and pathological correlations between the groups were studied.

RESULTS:

Forty-seven patients underwent tumor molecular profile testing, NA-ChRT, and completion surgery. Compared to the no-driver mutation group, the driver mutation group had lower MPR (23% vs 71%, p = 0.003), pCR (0% vs 26%, p = 0.02), and higher MRTC (43.4% vs 15.8%, p = 0.009). Univariate analysis showed an increased MPR rate for smokers, squamous cell histology, ChRT-surgery interval >65 days, and no-driver mutations. Multivariate analysis showed that only no-driver mutations (OR 0.39, p = 0.02) remained significant for MPR. PD-L1 status did not affect MPR. At 2 years, the driver mutation group had lower rates of local control (Hazard ration [HR] 0.67, p = 0.17) and disease-free survival (HR 0.5, p = 0.001). Overall survival was similar for both groups (HR = 1.04, p = 0.86).

CONCLUSION:

Following 60 Gray NA-ChRT, tumors with a driver mutation had lower MPR and pCR rates than tumors without a driver mutation. PD-L1 was not associated with tumor regression.

ADVANCES IN KNOWLEDGE:

Patients with resectable LA-NSCLC and an EGFR driver mutation treated with neoadjuvant-ChRT and completion surgery have reduced pathologic regression, lower local control rates, and shorter disease-free survival than patients without a driver mutation. Evaluation of molecular testing should be introduced in LA-NSCLC intended for prognostication and treatment decisions.

• Authors: Sarit Appel, Jair Bar, Akram Saad, Edith Michelle Marom, Damien Urban, Amir Onn, Hadas Gantz-Sorotsky, Ran Yosef Kremer, Alon Ben-Nun, Marina Perelman, Efrat Ofek, Rinat Yacobi, Sameh Daher, Adi Rasco, Zvi Symon, Yaacov Richard Lawrence, Jeffrey Goldstein
• Journal: The British journal of radiology (Br J Radiol) Vol. 96 Issue 1152 Pg. 20220763 (Dec 2023) ISSN: 1748-880X [Electronic] England
• PMID: 37751214 (Publication Type: Journal Article)

Chemical References

• ErbB Receptors
• EGFR protein, human

Topics

• Humans
• Carcinoma, Non-Small-Cell Lung (genetics, therapy)
• Lung Neoplasms (therapy, drug therapy)
• Neoadjuvant Therapy
• ErbB Receptors (genetics)
• Mutation