The Treatment Strategy Of Radiotherapy Combined With EGFR-TKI In Advanced Non-small Cell Lung Cancer Patients

Part I:Continued EGFR-TKI combined with radiation therapy as subsequent treatment for advanced non-small cell lung cancer patients developing local failure from upfront EGFR-TKI treatmentPurpose:Non-small cell lung cancer(NSCLC)is a common malignancy with high morbidity and mortality worldwide.Epidermal growth factor receptor-tyrosine kinase inhibitor(EGFR-TKI)is the first-line treatment for advanced NSCLC patients with mutant EGFR.However,the majority of patients developed systemic or local progression because of EGFR-TKI acquired resistance.Nowadays,there is still no consensus after drug resistance.For limited disease,continuous EGFR-TKI with local treatment such as radiotherapy,may be a doable choice.This study aimed to evaluate the feasibility of continued EGFR-TKI plus local radiotherapy in NSCLC patients.Methods:Advanced NSCLC patients with EGFR active mutation,who received first-line or second-line EGFR-TKI therapy were treated with continued EGFR-TKI followed by local radiotherapy when locally progressive lesions were found.All patients’ medical data were collected to analyze tumor time to progression(TTP),tumor response rate,overall survival(OS)and adverse events(AEs).Results:A total of 50 irradiated lesions from 44 patients were included.Median TTP and PFS of 31 measurable lesions were both significantly prolonged after local radiation therapy(TTP 1 +TTP 2 vs.TTP 1: 21.7 months vs.16.0 months,P= 0.010;PFS1 + PFS2 vs.PFS1: 21.3 vs.16.0 months,P = 0.027).For 50 irradiated lesions,objective response rate and local control rate were 54.0% and 84.0%,respectively.Median OS was 26.6 months(95% CI 22.2 months to 31.0 months).There were no serious AEs no matter before or after radiotherapy.Conclusions:Radiotherapy is an effective method to control local progression or recurrence of advanced NSCLC.The treatment modality of continued EGFR-TKI combined with local radiation therapy is considerable for EGFR-mutant NSCLC patients with limited progressive disease.Part II:Concurrent EGFR-TKI and Thoracic Radiation Therapy in EGFR Active Mutation for the First-Line Treatment of Non-Small Cell Lung Cancer at Stage IVPurpose:In part I of the study,we have assessed and discussed the efficacy and feasibility of continued EGFR-TKI and concurrent radiotherapy to prolong time to tumor progression in EGFR-TKI treated patients developing local progression.However,what is the optimal pattern of EGFR-TKI combining with radiotherapy is still unclear.EGFR-TKI has been the first line treatment for EGFR mutant NSCLC patients.But the majority of patients got acquired resistance after a favorable response to EGFR-TKI on average 9-13 months,so there are questions that whether EGFR-TKI alone is enough and whether the combination of EGFR-TKI with concurrent thoracic radiotherapy(TRT)benefits clinically in these patients.Considering the findings in part I and the increased radiosensitivity by EGFR-TKI in other preclinical studies,we assume that EGFR-TKI with TRT as first-line treatment would be superior to it alone in NSCLC patients at stage IV.Methods:This is a single-arm,open-label,phase II study in which NSCLC patients with EGFR active mutation get first-line treatment that combines EGFR-TKI(erlotinib 150 mg or gefitinib 250 mg per day)with concurrent TRT(within 2 weeks,p GTV54~60Gy/27~30F/5.5~6w).A total of 30 patients may be needed.The primary endpoint is 1-year rate of PFS and the second endpoints are overall survival(OS),objective response rate(ORR),disease control rate(DCR)and adverse events(AEs).Results:Up to March 31,2017,there were nine patients recruited,who all received first-line EGFR-TKI concomitant with TRT.Five of the nine patients developed progressive disease,among whom three patients passed away.Seven patients were evaluated as PR and two patients as SD after periods of the treatment.There were six and two patients with grade 1~2 rash and diarrhea,respectively.And three patients had radiation-related adverse events,among whom one had grade 4 radiation pneumonitis.As for PFS and OS,the data were immature to be analyzed.Conclusions:The treatment strategy of EGFR-TKI concurrent with TRT was favorable to improve local tumor control.And the common AEs associated with EGFR-TKI combined with TRT seen in the study were tolerated.