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Background: Adjuvant chemotherapy (ACT) is considered for high‐risk patients in stage IB lung adenocarcinoma (LUAD). However, these risk factors are recognized as negative prognostic factors, not as predictors of ACT efficacy. This study aimed to analyze the efficacy of ACT in stage IB patients by retrospectively examining patients who had recurrence. Methods: We reviewed 1399 patients with stage IB (American Joint Committee on Cancer 7th edition) LUAD from 2012 to 2017 in our institution and found 147 patients with recurrence. The last follow‐up date was December 30, 2021. One‐to‐one propensity‐score matching (PSM) was used to reduce the potential selection bias. Results: Fifty‐five (37.4%) patients had received ACT and 92 (62.6%) had not (non‐ACT). Patients with ACT were younger (p < 0.001), had larger tumors (p < 0.001) and more lymphovascular invasion (p = 0.02), and seemed to have less distant recurrence (p = 0.001). After PSM, 110 patients were matched and baseline characteristics were balanced. ACT was not associated with improved disease‐free survival (DFS) after matching (mDFS = 23.5 m for ACT vs. 29.5 m for non‐ACT, p = 0.13). ACT failed to prolong DFS of patients in the extracranial recurrence subgroup and EGFR mutation subgroups, and was even associated with shorter DFS in intracranial relapsed patients (mDFS = 30.3 m vs. 33.5 m, p = 0.083) and patients with tumor ≤30 mm (mDFS = 21.9 m vs. 30.8 m, p = 0.076). Conclusion: In patients who were destined to develop recurrence after completely resected stage IB LUAD, ACT might not be associated with improved DFS. Further large multicenter studies are warranted to validate these findings. [ABSTRACT FROM AUTHOR]

Objective: Circulating tumor DNA (ctDNA) monitoring proves to be a promising approach to assess response and predict survival in epidermal growth factor receptor (EGFR)‐mutated non‐small‐cell lung cancer (NSCLC) patients treated with tyrosine kinase inhibitors (TKIs). However, whether the dynamic changes in ctDNA EGFR mutation status have the same predictive value as ctDNA remains unknown. This study aims to explore the predictive value of dynamic changes in both ctDNA and ctDNA EGFR status. Methods: A retrospective analysis was performed using 91 ctDNA samples from a cohort of 28 patients who were diagnosed with EGFR‐mutated NSCLC and treated with EGFR‐TKIs, including 14 patients treated with first‐/second‐generation TKIs and 14 treated with osimertinib. Blood samples at baseline (BL), within 4 weeks after TKI initiation (Week4), within 12 weeks before progression (pre‐PD), and at progression were collected. The relationship alternatives in ctDNA status, ctDNA EGFR status and response to EGFR‐TKIs as well as progression‐free survival (PFS) were analyzed. Results: We categorized 20 BL‐ctDNA positive patients with available Week4‐ctDNA into two groups: ctDNA‐clearance (N = 7, 35%) and ctDNA‐non‐clearance (N = 13, 65%). The ctDNA‐clearance group had better PFS than the ctDNA‐non‐clearance group (ctDNA‐clearance vs. ctDNA‐non‐clearance, p = 0.091, hazard ratio [HR] = 0.42, 95% confidence interval [CI] = 0.15–1.19). According to Week4‐EGFR status, we observed that PFS was significantly longer in EGFR‐clearance patients than EGFR‐non‐clearance groups, (p = 0.011, HR = 0.23, 95% CI = 0.08–0.72). We then categorized patients into three subgroups according to Week4‐ctDNA and Week4‐EGFR status: non‐clearance (N = 9), only‐EGFR‐clearance (concomitant alterations non‐clearance) (N = 4), and all‐clearance (N = 7). The nonclearance group had a significantly worse PFS than the all‐clearance group (median PFS = 5.07 vs. 11.40 months, p = 0.029, HR = 3.45, 95% CI = 1.05–11.49). The only‐EGFR‐clearance group had a similar PFS to the all‐clearance group (p = 0.607), which was longer than that of the non‐clearance group (median PFS = 9.20 vs. 5.07 months, p = 0.060, HR = 0.25, 95% CI = 0.05–1.18). We found that the all‐clearance group had a similar objective response rate (ORR) to the only‐EGFR‐clearance group (p = 1.000) and a higher ORR than the non‐clearance group (p = 0.012). Conclusion: Monitoring of EGFR clearance in ctDNA is promising and cost‐effective in assessing response and predicting survival in EGFR‐mutated NSCLC patients treated with EGFR‐TKIs, with similar predictive value to ctDNA surveillance. [ABSTRACT FROM AUTHOR]

Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have improved the prognosis of mutant lung cancer; however, the clinical application value of TKIs for nonclassical EGFR mutation is unclear, especially for patients with rare uncommon mutations. Methods: A retrospective study based on electronic medical records was conducted to collect data on the effectiveness of afatinib in patients with stage IIIB/IV lung adenocarcinoma (LUAD) bearing uncommon mutations between January 2017 and January 2021. Results: Forty‐two patients with uncommon mutations treated with afatinib were enrolled. The objective response rate (ORR) was 50.0% (10 of 20 patients). The median time to treatment failure (TTF) was 11.7 months (95% confidence interval = 8.5–18.3 months). Of the 42 patients, the median TTF was 15.0, 11.7, and 16.6 months in patients with Gly719Xaa (G719X), Ser768Ile (S768I), and Leu861Gln (L861Q) mutations, respectively. In patients with the rare uncommon mutation, the median TTF was 10.0 months, and the ORR was 50.0%. Afatinib demonstrated clinical activity across a set type of specific rare uncommon mutations, including EGFR L747P, A767_V769dup, and L833V/H835L, with a case having a TTF of more than 1 year. Molecular profiling reports of 16 afatinib‐resistant biopsy samples were available, and the secondary T790M mutation was detected in one patient with L833V/H835L mutation and one harboring S768I/L858R mutation. Conclusions: Our findings suggested that afatinib is effective in patients with uncommon mutations. Mechanisms of afatinib resistance vary and need further investigation. [ABSTRACT FROM AUTHOR]

Background: Transformation to small cell lung cancer (SCLC) is a resistance mechanism of epidermal growth factor receptor (EGFR) mutant lung adenocarcinoma (LADC) patients treated with EGFR tyrosine kinase inhibitors (TKIs). Here, we describe the clinical characteristics and prognosis of these patients and explore the treatment modes after transformation. Methods: EGFR‐mutant LADC patients with SCLC transformation were retrospectively included in the study. Demographic and clinical data were collected. Survival outcomes and corresponding influential factors were analyzed. Results: Twenty‐nine patients were included in the study. The median progression‐free survival (PFS) of patients who received first‐line EGFR‐TKIs was 13.1 months. The median time to SCLC transformation was 27.5 months. After transformation, the objective response rates of patients who received first‐line chemotherapy with or without EGFR‐TKIs were 43.8% and 37.5%, respectively. The median PFS of patients reveiving chemotherapy with EGFR‐TKIs was significantly longer than that of patients receiving chemotherapy without EGFR‐TKIs (5.2 vs. 3.0 months; HR, 0.19; 95% CI: 0.05–0.72; p = 0.014). However, there was no significant difference in median overall survival (OS) between patients who received chemotherapy with or without EGFR‐TKIs (14.8 vs. 13.0 months; p = 0.474). In the multivariate Cox proportional hazards regression analysis, both anti‐angiogenic treatment (HR, 0.04; 95% CI: 0.01–0.29; p = 0.001) and local radiotherapy (HR, 0.28; 95% CI: 0.08–0.97; p = 0.044) were significantly associated with better patient OS after transformation. Conclusions: Compared with chemotherapy alone, the combination of chemotherapy and EGFR‐TKIs as first‐line treatment after SCLC transformation can benefit patients in PFS but not in OS. However, anti‐angiogenic therapies and local radiotherapy can significantly prolong OS after transformation. [ABSTRACT FROM AUTHOR]

Background: Previous studies have demonstrated that PD‐1 inhibitors are effective in the treatment of advanced or metastatic non‐small cell lung cancer (NSCLC). However, whether the combination of PD‐1 inhibitors and antiangiogenic agents benefit advanced NSCLC patients as subsequent therapy remains unknown. In this study, we retrospectively reviewed the efficacy and safety profile of this combination strategy as subsequent therapy for NSCLC patients in a real‐world setting. Methods: A total of 30 patients with advanced NSCLC, who progressed after at least two cycles of platinum‐based chemotherapy or targeted therapy and subsequently received combination therapy with a PD‐1 inhibitor and antiangiogenic agent, were included in this study. The safety profile and efficacy were also investigated. Results: At the time of a median follow‐up period of 10.7 months, 28 patients had experienced progression of disease and 16 patients had died. The median progression‐free survial (mPFS) was 5.0 months (95% confidence interval [CI]: 3.179–6.821), and the median overall survival (mOS) was 14.3 months (95% CI: 8.912–19.659). The objective response rate (ORR) and the disease control rate (DCR) were 10.3% and 72.4%, respectively (0 complete remission, three partial responses and 18 stable disease in 29 patients with measurable lesions). Patients with PD‐L1 expression of at least 1% of tumor cells (n = 5) had relatively longer mPFS compared to those with PD‐L1‐negative tumors (n = 14), (11.6 months vs. 3.7 months). Treatment was suspended in two patients due to grade 3 immune‐related pneumonia and pancreatitis, respectively. No novel adverse events (AEs) or grade 4 AEs were observed. Conclusions: A combination of PD‐1 inhibitors and antiangiogenic targeting agents may be beneficial for patients with advanced or metastatic NSCLC as subsequent treatment, especially for patients with PD‐L1 protein expression positive, and treatment is well tolerated. [ABSTRACT FROM AUTHOR]

Background: Previous studies have demonstrated the combination of epidermal growth factor receptor (EGFR)‐tyrosine kinase inhibitors (TKIs) and other antitumor agents may delay drug resistance. In this study, we retrospectively reviewed the efficacy and safety of first‐line concurrent EGFR‐TKIs and platinum‐based doublet chemotherapy with or without an antiangiogenic agent for advanced lung adenocarcinoma patients in the real world. Methods: A total of 30 patients with advanced lung adenocarcinoma and activating EGFR mutations concurrently received an EGFR‐TKI and platinum‐based doublet chemotherapy with or without bevacizumab. The safety profile and efficacy were retrospectively reviewed. Results: At the median follow‐up time of 22.1 months, 18 patients had experienced disease progression, and six patients had died because of disease. The median progression‐free survival (mPFS) was 21.2 months (95% CI: 12.631–29.798). Of the 28 patients who had measurable lesions, the objective response rate and disease control rate were 71.4% and 96.4%, respectively (one patient achieved complete remission, 19 patients had a partial response and seven patients had stable disease). Male patients had significantly longer mPFS than female patients (32.6 vs. 14.6 months, HR = 3.593, 95% CI: 1.158–11.148, p = 0.027). The most frequently seen grade 3/4 adverse events were hematological toxicities, seen in three cases (10%). Three patients ceased bevacizumab due to vascular events, including hypertension (grade 2, 6.7%) and venous thrombosis (grade 2, 3.3%), and continued EGFR‐TKI and platinum‐based doublet chemotherapy. Conclusions: The combination of first‐generation EGFR‐TKIs with platinum‐based chemotherapy may be a first‐line treatment for advanced lung adenocarcinoma patients harboring activated EGFR mutations and is well tolerated. [ABSTRACT FROM AUTHOR]