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Background: Src homology region 2 domain‐containing phosphatase 2 (SHP2) is a novel target for Kirsten rat sarcoma oncogene (KRAS) mutant cancer. We retrospectively studied the significance of SHP2 in KRAS mutant non‐small cell lung cancer (NSCLC) treated with immunotherapy and its relationship with tumor microenvironment (TME). Methods: Sixty‐one advanced KRAS mutant NSCLC patients who underwent immunotherapy were enrolled. Next‐generation sequencing (NGS) was used to profile mutation status. The expression of SHP2, phospho‐SHP2 (pSHP2), and programmed death ligand 1 (PD‐L1) were analyzed by immunohistochemistry (IHC). Quantitative multiplexed immunofluorescence cytochemistry (mIFC) analysis was conducted to describe the TME. Results: SHP2 was heterogeneously expressed in 32 samples in both tumor cells and immune cells and highly expressed (H‐score >10) in 25 (78.1%) samples. The expression levels of SHP2 and pSHP2 were positively correlated. Stromal SHP2 (s‐SHP2) was higher in tumors with PD‐L1 ≥50% versus PD‐L1 <50% (p = 0.039). By quantitative mIFC analysis, the expression of s‐SHP2 had positive correlation with CD8, CD4, CD68, and PD‐L1 levels in stromal area. Patients with high SHP2 expression made up 100.0% of the partial respond (PR) and 80.0% of the stable disease (SD), whereas 50.0% of the progress disease (PD). High SHP2 expression was associated with longer progression‐free survival (PFS) and overall survival (OS) (p < 0.001, p = 0.013). Patients with high expression of both SHP2 and PD‐L1 had longer PFS (p < 0.001). Conclusion: High SHP2 expression could predict the efficacy of immunotherapy and better survival in advanced KRAS mutant NSCLC. SHP2 may function in both tumor cells and immune cells, warranting further study on the potential diverse effects of SHP2 inhibition in TME. [ABSTRACT FROM AUTHOR]

Background: Previous trials have suggested that elderly patients with non‐small‐cell lung cancer (NSCLC) could benefit from nanoparticle albumin‐bound paclitaxel (nab‐paclitaxel). Real‐world data on the elderly Chinese population are lacking. This study aimed to analyze the effectiveness and tolerability of nab‐paclitaxel in Chinese elderly patients (≥65 years) with advanced NSCLC. Methods: This study included 76 patients with a primary diagnosis of IIIB‐IV NSCLC from January 2010 to December 2017 at Peking University Cancer Hospital, who received nab‐paclitaxel (125 or 130 mg/m2 i.v.) every three weeks. The overall survival (OS), progression‐free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs) were analyzed. Results: There were 12 patients who received nab‐paclitaxel as the first‐line treatment (seven also received carboplatin), and 64 received nab‐paclitaxel as the latter‐line treatment. The overall ORR, DCR, median PFS, and median OS were 14.5%, 69.7%, 5.2 months, and 12.2 months, respectively. The Eastern Cooperative Oncology Group performance status of one and the age of 70–74 years were independently associated with longer OS, while early treatment line of nab‐paclitaxel and age of 70–74 years were independently associated with longer PFS. The most common AEs were anemia, leukopenia, gastrointestinal reaction, fatigue, and peripheral neuropathy, which were all manageable. Dose adjustment or treatment discontinuation was encountered in 10 patients because of AEs. The incidence of AEs was not different among age subgroups. Conclusions: Nab‐paclitaxel has a good clinical response profile in Chinese elderly patients with stage IIIB–IV NSCLC. Prospective clinical trials are needed to confirm these results. Key points: Significant findings of the study: Nanoparticle albumin‐bound paclitaxel (nab‐paclitaxel) has a good clinical response profile in Chinese elderly (≥65 years) patients with stage IIIB‐IV non‐small‐cell lung cancer (NSCLC), with acceptable and manageable adverse events. What this study adds: Preliminary evidence shows a good clinical response from treatment with nab‐paclitaxel in Chinese elderly patients with advanced NSCLC. [ABSTRACT FROM AUTHOR]

Background: Primary tumors located in the right and left side have distinctive prognoses, but the details have not been fully identified in non‐small cell lung cancer (NSCLC). This study investigated the impact of primary tumor side on long‐term survival in NSCLC patients. Methods: Data of 90 407 patients from the Surveillance, Epidemiology, and End Results (SEER) Program were analyzed. To avoid bias between groups, we used innovative propensity score matching (PSM) analysis. Results: There was no significant distinction in overall survival (OS) between right (n = 53 496) and left (n = 36 911) side tumors (hazard ratio [HR] 0.993, 95% confidence interval [CI] 0.9756–1.011; P = 0.432). Left side was associated with superior five‐year cancer‐specific survival (CSS) compared to right side NSCLC (HR 0.977, 95% CI 0.9574–0.9969; P = 0.024). No significant difference was observed in OS (P = 0.689) or CSS (P = 0.288) after PSM analysis. In the 51 319 patients who underwent surgery, left side (n = 21 245) was associated with poor OS compared to right side (n = 30 074) NSCLC (HR 1.039, 95% CI 1.011–1.067; P = 0.006), while CSS was similar (HR 1.031, 95% CI 0.997–1.065; P = 0.069). In patients who underwent surgery, there was also no significant difference in OS (P = 0.986) or CSS (P = 0.979) after PSM analysis. Conclusion: The prognosis between right and left side NSCLC in stage I–IIIA was similar regardless of whether patients underwent surgery. Primary tumor side cannot be considered a prognostic factor when choosing appropriate treatment. [ABSTRACT FROM AUTHOR]

Background: We evaluated topoisomerase I (TOPO1) expression in patients with small cell lung cancer (SCLC) and identified predictive factors for the efficacy of second‐line topotecan chemotherapy. Methods: We retrospectively evaluated the records of SCLC patients treated in our department from January 2007 to December 2016 who received second‐line topotecan chemotherapy. Patients with archived tumor samples were enrolled. TOPO1 expression levels were evaluated by immunohistochemistry, and the relationships between TOPO1 expression, clinical factors, chemotherapy efficacy, and survival were analyzed. Results: Of the 78 patients enrolled, 67 showed TOPO1 expression (85.9%). Patients were divided into strong (n = 43) or weak (n = 35) expression groups based on staining intensity. Disease control rates for topotecan were 39.5% and 14.3% in the strong and weak groups, respectively (P = 0.014). Second‐line median progression‐free survival was 2.2 and 2.0 months (P = 0.057), and median overall survival was 8.1 and 6.0 months (P = 0.199) in the strong and weak positive groups, respectively. Patients were also divided into sensitive (n = 47) and refractory (n = 31) disease groups according to the duration from the onset of first‐line therapy to relapse. Median second‐line progression‐free survival was 2.2 and 1.8 months in the sensitive and refractory relapse groups, respectively (P = 0.005). Conclusions: TOPO1 expression was prevalent in SCLC patients. Strong expression was associated with an elevated disease control rate after second‐line topotecan chemotherapy. Patients with sensitive disease that relapsed after first‐line chemotherapy had better survival than refractory patients who received second‐line topotecan chemotherapy. [ABSTRACT FROM AUTHOR]

Background: ALK‐tyrosine kinase inhibitors (TKIs) have been proven effective for treating ALK‐positive non‐small cell lung cancer (NSCLC), although patients present with variable responses and disease progression courses. The detailed underlying molecular mechanisms require further investigation to yield a better prognosis. Methods: Targeted next‐generation sequencing (NGS) mutation profiling was performed on samples from 42 NSCLC patients confirmed positive for ALK rearrangements by fluorescence in situ hybridization or immunohistochemistry who experienced disease progression after crizotinib treatment. Results: ALK rearrangements were not confirmed in six patients (14%) with other potential oncogenic drivers identified by NGS, who therefore did not respond to crizotinib and had significantly shorter overall survival (OS) compared to NGS ALK ‐positive patients. Fifteen ALK activating mutations were detected in 8 out of 26 post‐treatment samples (31%), among which ALK L1196M and G1269A were the most common acquired mutations detected in half of the patients with ALK activating mutations. Dynamic monitoring of the genetic evolution in one patient revealed both spatial and temporal heterogeneity of resistant mechanisms during different ALK‐TKI treatment courses. Activation of ALK downstream or bypass pathways was detected in patients without ALK activating mutations, such as genetic alterations in PIK3CA, MET, and KRAS. Interestingly, we identified two patients with acquired mutations in the DNA mismatch repair gene POLE, which resulted in a dramatically increased tumor mutation burden, and might contribute to the poor response to crizotinib. Conclusions: Heterogeneous resistant mechanisms have been identified and correlate to diverse responses to crizotinib. Comprehensive and dynamic mutation profiling is required to better predict clinical outcomes. [ABSTRACT FROM AUTHOR]