Clinical features and therapeutic options in non‐small cell lung cancer patients with concomitant mutations of EGFR, ALK, ROS1, KRAS or BRAF

Abstract

Background Although oncogenic driver mutations were thought to be mutually exclusive in non‐small cell lung cancer (NSCLC), certain tumors harbor co‐occurring mutations and represent a rare molecular subtype. The evaluation of the clinical features and therapeutic response associated with this NSCLC subtype will be vital for understanding the heterogeneity of treatment response and improving the management of these patients. Methods This retrospective study included 3774 samples from patients diagnosed with NSCLC. All samples were screened for EGFR, ALK, ROS1, KRAS, and BRAF mutation using the amplification‐refractory mutation system. The relationship between concomitant driver mutations and clinicopathologic characteristics, and patient clinical outcomes were evaluated. Results Sixty‐three (1.7%) samples had more than one driver gene mutation. Among these, 43 were coalterations with an EGFR mutation, 20 with an ALK rearrangement, and eight with an ROS1 rearrangement. Except for ROS1 concomitant mutations that were more frequent in male patients (87.5%, P = 0.020), the clinicopathological features of the concomitant mutation patients were not significantly different from those harboring a single EGFR, ALK, or ROS1 mutation. Furthermore, first‐line EGFR‐TKI treatment did not significantly improve the progression‐free survival (PFS) of patients harboring EGFR concomitant mutation, compared to patients harboring a single EGFR mutation. However, for EGFR concomitant mutation patients, TKI therapy was more effective than chemotherapy (median PFS of 10.8 vs 5.2 months, P = 0.023). Lastly, KRAS mutations did not influence the EGFR‐TKI therapy treatment effect. Conclusion In this study, concomitant mutations were found in 1.7% of the NSCLC. EGFR‐TKI therapy was more effective than chemotherapy for patients harboring EGFR concomitant mutation, and ROS1 concomitant mutations were more frequent in male patients. For patients harboring coalterations with an ALK or ROS1 rearrangement, we should be cautious when considering the therapeutic options.

Actionable Mutation Profiles of Non-Small Cell Lung Cancer patients from Vietnamese population

“…Our findings were consistent with our previous study using the same panel of genes and reporting a similar mutation rate of 63.6% in a smaller cohort of 59 Vietnamese NSCLC patients 32 . The mutation profiles of Vietnamese NSCLC patients also exhibited certain common features of NSCLC patients previously reported 33,34 . Firstly, mutations in EGFR and KRAS are the most common, accounted for more than 50% of total cases, while mutations in ALK, BRAF, NRAS and ROS1 were rarer.…”

Molecular and clinical analysis of Chinese patients with anaplastic lymphoma kinase (ALK)‐rearranged non‐small cell lung cancer

“…Additionally, several studies have reported that different orders of treatment lines of EGFR‐TKI and ALK‐TKI affect the therapeutic outcomes of this subgroup of patients . Moreover, numerous studies reported that EGFR mutation and ALK rearrangements may coexist in the same tumor cells or may occur in different lesions of the tumor, which may have an effect on the treatment strategies . As ctDNA was released from tumor lesions of the whole body, the result of ALK/EGFR co‐alteration from ctDNA should be further verified by tissue samples from different tumor foci in patients with multifocal NSCLC if possible, in order to clarify the intratumoral or intertumoral coexistence of such co‐alteration and guide the subsequent therapy.…”

Status of 10 targeted genes of non‐small cell lung cancer in eastern China: A study of 884 patients based on NGS in a single institution

“…A previous study showed that targetable activating alterations in lung cancer genes, such as EGFR, ALK, RET and ROS1, are mutually exclusive molecular events. 30 Recently, however, some cases of NSCLC with coalteration have been reported in the literature, [38][39][40][41] and these coaltered patients may benefit from treatment with more than one targeted drug. 42 There were 33 cases (3.7%) with coalteration in our study, including EGFR/PIK3CA (2.1%, 19 cases), EGFR/HER2 (0.7%, six cases), HER2/KRAS (0.3%, three cases), EGFR/KRAS (0.1%, one case), EGFR/ ROS1 (0.1%, one case), EGFR/NRAS (0.1%, one case), KRAS/PIK3CA (0.1%, one case), and a triple KRAS/ PIK3CA/HER2 (0.1%, one case) coalteration.…”

“…43 PIK3CA mutations frequently coexist with EGFR or KRAS mutations. Evidence has suggested that the combination of KRAS and EGFR mutation may have a negative impact on the efficacy of TKI treatment, 41 but EGFR-TKI may be an effective choice for the treatment of patients with NSCLC with comutation of EGFR/KRAS. 44 Zeng et al 45 reported a case of adenocarcinoma having acquired GOPC-ROS1 rearrangement after treatment with osimertinib.…”