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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: For advanced nonsquamous non‐small cell lung cancer (NSCLC), the mechanisms of resistance to first‐line immunotherapy are not clear. Immune checkpoint inhibitors (ICIs) in combination with agents targeting other pathways may serve as second‐line therapy options. Apatinib (a vascular endothelial growth factor receptor 2 tyrosine kinase inhibitor) could increase the efficacy of camrelizumab (an ICI agent). The efficacy and safety of this combination regimen as a second‐line therapy for NSCLC patients after failure on first‐line immunotherapy has not previously been evaluated. Methods: In this single‐arm, multicenter, phase II trial, metastatic nonsquamous NSCLC patients previously treated with single‐agent ICI or ICI plus chemotherapy will be enrolled. Participants will receive intravenous camrelizumab 200 mg D1 and oral apatinib 250 mg D1‐21 for a 21‐day cycle. The study treatment will continue until disease progression, unacceptable toxicity, or withdrawal of consent. The primary endpoint is progression‐free survival by investigator. Secondary endpoints are overall survival, objective response rate, disease control rate, duration of response by investigator, quality of life, safety, and toxicity. Conclusions: This trial will provide evidence of the benefit of treatment with camrelizumab combined with apatinib in advanced nonsquamous NSCLC patients who were previously treated with first‐line immunotherapy. [ABSTRACT FROM AUTHOR]

Background: Tyrosine kinase inhibitors (TKIs) can significantly prolong overall survival for patients with advanced non‐small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR)‐mutation or anaplastic lymphoma kinase (ALK)‐rearrangement. However, the real‐world evaluation status of ALK/EGFR in China remains unclear. Methods: We conducted a prospective study including 1134 patients with cytologically or histologically confirmed advanced NSCLC (stage IIIb–IV) at 12 Chinese hospitals. Results: The most common evaluation methods were amplification‐refractory mutation system for EGFR status and immunohistochemistry targeting D5F3 for ALK status. Among patients with non‐squamous, the EGFR mutation rate was 44.1% and the ALK rearrangement rate was 10.0%. Among patients with squamous cell carcinoma, the EGFR mutation rate was 8.3% and the ALK rearrangement rate was 3.7%. Among all patients, gender (HR = 1.7, 95%CI = 1.2–2.4, P = 0.006), smoking history (HR = 1.8, 95%CI = 1.3–2.7, P = 0.001), histology (HR = 5.0, 95%CI = 2.4–10.1, P < 0.001), and brain metastases (HR = 1.5, 95%CI = 1.1–2.2, P = 0.017) were independent predictors of EGFR mutation, while age (HR = 2.6, 95%CI = 1.7–4.1, P < 0.001) was an independent predictor of ALK rearrangement. The median time from tumor diagnosis to EGFR or ALK status confirmation was 7 and 5 days, respectively. Targeted therapy rate was 73.8% in EGFR‐positive patients and 51.4% in ALK‐positive patients. There was a negative correlation between the first‐line targeted therapy rate and the EGFR mutation detection period (r = −0.152, P = 0.02), while no significant correlation among patients with ALK rearrangement (r = −0.179, P = 0.076). Conclusion: Squamous NSCLC patients should also be routinely tested to determine their EGFR/ALK statuses. The first‐line targeted therapy rate remains low in Chinese patients with NSCLC. [ABSTRACT FROM AUTHOR]

Background: Crizotinib is associated with a favorable survival benefit in patients with ALK‐positive non‐small cell lung cancer (NSCLC); however, a subset of patients harboring ALK rearrangement shows a poor response. Methods: We collected the clinical features and survival outcomes of 28 primary‐resistant responders (PRR) with progression‐free survival (PFS) of < 3 months on crizotinib and compared these with 78 long‐term responders (LTR) that achieved > 24 months PFS (control). Results: Primary resistance was observed in 6.5% of the patients. The median PFS of the PRR and LTR groups was 1.2 months (95% confidence interval [CI] 0.70–1.73) and 47.0 months (95% CI 34.39–59.64), respectively. A better Eastern Cooperative Oncology Group performance status score was significantly associated with longer PFS (odds ratio 0.06, 95% CI 0.01–0.33; P = 0.001). The median overall survival (OS) of the PRR group was 8.4 months (95% CI 3.47–13.42) and crizotinib as first‐line treatment was an independent predictive factor for survival outcome (P = 0.005). Patients administered ALK‐tyrosine kinase inhibitors after crizotinib progression had significantly longer survival than the PRR group treated with best supportive care (P = 0.007), but no significant difference was found between ALK‐tyrosine kinase inhibitor treatment and single chemotherapy (P = 0.944). Conclusion: Patients with primary resistance to crizotinib displayed unfavorable survival outcomes and the underlying mechanism cannot be identified in clinical features. Nevertheless, next‐generation ALK inhibitors and chemotherapy after crizotinib progression could confer a therapeutic and survival benefit in this population. [ABSTRACT FROM AUTHOR]

Background: Crizotinib has demonstrated favorable efficacy in patients with advanced ALK‐positive non‐small cell lung cancer (NSCLC). Unfortunately, the majority of ALK‐positive patients ultimately develop acquired resistance within one year after the initiation of crizotinib treatment; however, the estimation of overall survival (OS) beyond crizotinib resistance has not yet been fully demonstrated. The purpose of this study was to identify favorable predictors affecting survival outcome. Methods: In this single‐center retrospective study, the data of 136 patients with advanced ALK‐positive NSCLC beyond crizotinib resistance were analyzed between January 2013 and December 2017. Patients were divided into two groups according to intracranial or extracranial progression on crizotinib, and sequential therapies including crizotinib continuation with local therapy, next‐generation ALK inhibitors, and chemotherapy. The primary endpoint was the median OS duration from the start of crizotinib resistance to death or the last follow‐up. Univariate and multivariate Cox analyses of OS were carried out. Results: At the time of analysis, 60 (41.1%) of the 136 patients had died. Median progression free survival (PFS) and OS from the metastatic diagnosis were 10.4 and 41.3 months, respectively. Sequential therapies administered beyond crizotinib treatment were: next‐generation ALK inhibitors (54 patients), chemotherapy (20 patients), and crizotinib continuation with local therapy (62 patients). Multivariate Cox analysis revealed that long PFS with crizotinib (≥ 10.4 months), intracranial progression, and next‐generation ALK inhibitors were significantly associated with a decreased risk of death. Conclusion: Long PFS with crizotinib (≥10.4 months), intracranial progression, and use of next‐generation ALK inhibitors might be favorable predictors for OS in advanced ALK‐positive NSCLC patients. [ABSTRACT FROM AUTHOR]

Background: Bevacizumab (Bev) plus platinum‐based chemotherapy is a standard first‐line treatment option for advanced non‐squamous non‐small cell lung cancer (NS‐NSCLC). We evaluated the efficacy and safety of continuing Bev in Chinese patients with advanced NS‐NSCLC progression after first‐line treatment containing Bev in a real‐world setting. Methods: The data of 118 patients with advanced NS‐NSCLC who received Bev between July 2009 and July 2017 were retrospectively collected. The patients were divided into groups: 15 in Bev first‐line, 82 in Bev ≥ second‐line, and 21 in Bev cross‐lines. The primary endpoint was overall survival; secondary objectives were progression‐free survival, objective response rate, disease control rate, and safety. Results: The overall survival was 21.8, 32.5, and 18.9 months (P = 0.092) in the overall population and 39.3, 25.8, and 15.0 months (P = 0.347) in the wild‐type population in the Bev first‐line, Bev ≥ second‐line, and Bev cross‐lines groups, respectively. There were no significant differences in progression‐free survival of second‐line treatment between the groups in the overall population: 2.6, 3.7, and 3.2 months in the Bev first‐line, Bev ≥ second‐line, and Bev cross‐lines groups, respectively (P = 0.796). No statistically significant improvement in objective response or disease control rates in the Bev cross‐lines group was observed. No unexpected or severe adverse events were recorded. Conclusion: We found no benefit in continuing Bev treatment beyond progression after first‐line treatment containing Bev for patients with advanced NS‐NSCLC. Further research of validated predictive biomarkers of response to treatment after long‐term antiangiogenic therapy is required. [ABSTRACT FROM AUTHOR]

Background: Large scale randomized controlled trials have demonstrated that the use of bevacizumab in addition to chemotherapy in patients with advanced non‐small cell lung cancer (NSCLC) conveys significant survival benefits. We explored the clinical impact of a first‐line regimen containing bevacizumab (B+) versus a non‐bevacizumab regimen (non‐B) in advanced non‐squamous NSCLC (NS‐NSCLC) patients in a real world setting. Methods: The medical records of patients with advanced NS‐NSCLC who received first‐line therapy with or without bevacizumab were retrospectively collected. The primary outcome was progression‐free survival (PFS), with secondary objectives of objective response rate (ORR), disease control rate (DCR), and safety. Exploratory analysis of EGFR and ALK status was conducted in subgroup. Results: One hundred and forty‐nine patients met the selection criteria: 62 in the B+ and 87 in the non‐B group. The baseline characteristics were well balanced. In the overall population, the median PFS was significantly longer in the B+ than in the non‐B group (9.7 vs. 7.0 months, hazard ratio [HR] 0.52, 95% confidence interval [CI] 0.30–0.91; P = 0.0184). Improved trends in both ORR and DCR were observed in the B+ group. In wild‐type patients, the median PFS of the B+ was 11.3 compared to 5.5 months in the non‐B group (HR 0.43, 95% CI 0.20–0.91; P = 0.0234). In wild type and unknown populations, the median PFS was 11.3 (B+) compared to 6.0 months (non‐B) (HR 0.53; 95% CI 0.28–1.02; P = 0.0520). The safety profile was acceptable in both groups and no unexpected findings were observed. Conclusion: Our analysis confirmed that a first‐line regimen containing bevacizumab showed superior clinical benefits over a non‐bevacizumab regimen in Chinese patients with advanced NS‐NSCLC in a real world setting. [ABSTRACT FROM AUTHOR]

Background: EGFR‐tyrosine kinase inhibitors (TKIs) combined with TS‐1 might overcome EGFR‐TKI resistance, which has been indicated by several preclinical studies. We investigated the synergistic efficacy and safety of the combination therapy of EGFR‐TKIs and TS‐1 in non‐small cell lung cancer (NSCLC) patients with acquired resistance to previous EGFR‐TKI therapy. Methods: This was a phase II, single‐arm and single‐center prospective study. Stage IIIB–IV NSCLC patients with acquired resistance to prior EGFR‐TKI treatment were enrolled. All patients were administered combination therapy of TS‐1 and continuing EGFR‐TKIs in this study. The primary endpoints were progression‐free survival (PFS), while overall survival (OS), disease control rate (DCR), and safety were secondary endpoints. Results: A total of 42 patients with acquired resistance to EGFR‐TKIs were eligible for this study. The median PFS for all patients was five months (95% confidence interval [CI] 3.6–5.4). The OS and DCR were 31.9 (95% CI 17.8–46.0) months and 69.0% (29/42), respectively. No grade 4 toxicity or grade 3 hematologic toxicity was observed in this study. One patient (2%) experienced grade 3 elevated total serum bilirubin. Conclusion: The combination treatment of TS‐1 and EGFR‐TKIs was effective and well tolerated by patients who had experienced prior EGFR‐TKI treatment failure. Our results need to be validated by larger prospective clinical trials. [ABSTRACT FROM AUTHOR]

Background: The efficacy of pemetrexed-based first-line chemotherapy in anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) has been demonstrated in several studies; however, there is a lack of data from Chinese populations. Methods: The clinicopathological characteristics and treatment outcomes of 52 patients with ALK-positive advanced NSCLC who received pemetrexed as first-line chemotherapy at the Department of Medical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences were retrospectively reviewed. The primary end points were response rate and progression-free survival (PFS). Results: The gender proportion was balanced and the median age was 51 years (range 26-76). Of the 52 patients, 46 (88.5%) had stage IV disease, predominantly adenocarcinoma (98.1%). Sixteen patients were current/former smokers and 36 were never/light smokers. The most common sites of metastasis were the pleura (36.5%), bone (30.8%), lung (26.9%), and brain (17.3%). The median PFS was 9.5 months (95% confidence interval 7.454-11.536). At the time of analysis, partial remission was achieved in 18 (34.6%) patients, stable disease in 26 (50.0%), and progressive disease in eight (15.4%); none of the patients achieved complete remission. The objective response rate was 34.6% and the disease control rate was 84.6%. Common adverse events with pemetrexed were neutropenia (53.8%), nausea and vomiting (51.9%), leukopenia (32.7%), and fatigue (25.0%), mainly at grades 1 or 2. Conclusions: Pemetrexed is efficient and tolerated as first-line treatment for ALK-positive NSCLC in a cohort of Chinese patients and may prove to be an alternative option for the treatment of ALK-positive NSCLC. [ABSTRACT FROM AUTHOR]