Neoadjuvant immunotherapy in non-small cell lung cancer: a narrative review on mechanisms, efficacy and safety.

Background and Objective: Immune checkpoint inhibitors and immunotherapy have been shown to improve survival rates, especially in non-small cell lung cancer (NSCLC) patients. More recently, several trials have evaluated the clinical roles of immunotherapy as neoadjuvant settings for NSCLC. There trials suggested that neoadjuvant immunotherapy may effectively reduce the risk of the local recurrence and metastasis of cancer, and significantly improved overall survival and cure rates. Here we conducted a review to summarize the possible mechanism, clinical development, and research progress of neoadjuvant immunotherapy in NSCLC. Methods: Relevant articles for this review were retrieved from Google Scholar, Clinicaltrials.gov., and PubMed using the terms "non-small-cell lung cancer", "NSCLC", "neoadjuvant", "immunotherapy", "immune checkpoint inhibitors", "mechanisms", and "toxicity". The primary focus was placed on clinical studies and conference abstracts measuring the safety and efficacy of neoadjuvant immunotherapy in NSCLC until May 2022. Key Content and Findings: After reviewing the preclinical and clinical trial, the preclinical study showed that neoadjuvant immune checkpoint inhibitor promotes antitumor immunity through the enhancement of T cell effector function and the induction of long-term memory. The initial results of preliminary early-phase trials suggested that neoadjuvant immunotherapy is a promising therapeutic strategy for resectable NSCLC patients, with long-term response and modest toxicity, many of these regimens are currently being evaluated by randomized phase III trials. In addition, the major pathologic response of neoadjuvant immunotherapy ranged up to 45% in these studies when used alone, and up to around 83-86% when used in combination with chemotherapy, therefore it has been seen as a rather potent tumor debulking agent. Conclusions: Neoadjuvant immunotherapy has been shown to be a novel integral component of NSCLC care. However, there are also several research questions that requires further investigation, such as the side effects, the optimally treated patients, and the time of preoperative immunotherapy.

The Clinical Efficacy and Economic Benefits of Recombinant Human Thrombopoietin for the Treatment of Chemotherapy or Chemoradiotherapy-Induced Thrombocytopenia.

Even though cytopenia caused by either chemotherapy or radiotherapy is a common complication in cancer patients, chemoradiotherapy remains an essential treatment for the majority of patients. The purpose of this study was to look into the clinical efficacy and cost-effectiveness of recombinant human thrombopoietin (rhTPO) in treating chemo- or chemoradiotherapy-induced grade II, III, and IV thrombocytopenia. From December 2019 to November 2020, 233 lung cancer patients admitted to our hospital with chemotherapy- or chemoradiotherapy-induced thrombocytopenia were enrolled and treated with rhTPO. The study's findings revealed a significant disparity in the use of concurrent chemoradiotherapy in patients with grade II, III, and IV thrombocytopenia. All costs, including rhTPO treatment costs, platelet costs, drug costs, and nondrug costs, tended to rise as the severity of thrombocytopenia increased. In the treatment of chemotherapy or radiotherapy-induced thrombocytopenia, rhTPO has shown good clinical efficacy. In the treatment of grade II thrombocytopenia, rhTPO has a favorable economic evaluation. As a result, early intervention and thrombocytopenia treatment should be provided, which warrants further clinical investigation.

Treatment outcomes and prognosis of immune checkpoint inhibitors therapy in patients with advanced thymic carcinoma: A multicentre retrospective study.

BACKGROUND: Immunotherapy has demonstrated good efficacy and survival outcomes in solid tumours. However, efficacy data for immune checkpoint inhibitors (ICIs) in advanced thymic carcinoma are lacking. The present study aimed to assess the activity of ICIs in advanced thymic carcinoma. METHODS: A multicentre retrospective study was conducted to explore the efficacy and safety of ICIs for advanced thymic carcinoma. Objective response rate (ORR), progression-free survival (PFS), overall survival, and immune-related adverse events (irAEs) were analysed. In addition, factors independently associated with treatment efficacy and survival outcomes were evaluated. RESULTS: A total of 77 patients with advanced thymic carcinoma were enrolled between March 2016 and September 2021. The ORR was existing the difference between ICIs monotherapy (n = 23) and ICIs combined with chemotherapy (n = 54) (17.4% versus 44.4%, P = 0.024). The ICIs combination treatments were associated with better median PFS (mPFS) compared to ICIs monotherapy (12.7 months versus 2.1 months, P < 0.001). Notably, liver or brain metastasis was a poor prognostic factor of mPFS (1.8 months versus 3.5 months, P = 0.012) in the ICIs monotherapy group. In addition, mPFS for the first-line treatment (n = 27) was longer than that for ICIs as the second- or posterior-line treatment (n = 50) (P < 0.001). The incidence of irAEs was 54.5% (42/77) in the 77 enrolled patients. The incidence of grade 3-4 irAE was 15.6% (12/77). CONCLUSIONS: Immunotherapy is effective in advanced thymic carcinoma, especially for combination with chemotherapy showed promising antitumour activity, which indicates worthy of combination treatment strategy for further study. IrAEs also require close monitoring and management.

Novel HIVEP1-ALK fusion in a patient with lung adenocarcinoma demonstrating sensitivity to alectinib: a case report.

Background: Anaplastic lymphoma kinase (ALK) fusion is an important oncogenic driver in non-small cell lung cancer (NSCLC). Reports on the intergenic region (IGR) as an ALK fusion partner are rare. Here, we report the case of a patient with advanced NSCLC harboring a human immunodeficiency virus type I enhancer binding protein 1 (HIVEP1)-ALK fusion that responded effectively to alectinib. Case Description: A 60-year-old non-smoking male was referred with a 3-month history of productive cough secondary to lung adenocarcinoma metastatic to mediastinal lymph nodes, brain, liver, and bone (T2N3M1c, stage IVB). Next-generation sequencing identified an IGR (upstream HIVEP1-) ALK fusion, and immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) results were consistent with an ALK-positive tumor. The patient was subsequently started on alectinib, with no obvious adverse reaction. After 1 month of therapy, the patient achieved significantly remission of the clinical symptoms and had led to an ongoing partial response (PR) lasting >33 months. Conclusions: Our experience highlights the efficacy of alectinib in a patient with HIVEP1-ALK fusion positive NSCLC with multiple metastases including brain disease, and the need for multiple genetic testing methods to verify the oncogenicity of ALK fusions prior to treatment. It could provide useful guidance for the treatment of similar cases in the future.

Apatinib in patients with recurrent or metastatic thymic epithelial tumor: a single-arm, multicenter, open-label, phase II trial.

BACKGROUND: Thymic epithelial tumors (TETs) are rare malignancies and the treatment options are limited. We aimed to evaluate the efficacy and safety of apatinib, an angiogenesis inhibitor, in advanced TETs. METHODS: This was an open-label, single-arm, phase II trial at three centers in China. Patients with TET who had progressed after failure of at least one line of platinum-based chemotherapy were enrolled. Patients received apatinib 500 mg orally per day. The primary endpoint was objective response rate (ORR). Secondary endpoints were progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and safety. RESULTS: From June 29, 2017, to April 18, 2019, 25 patients were enrolled. At data cut off (September 30, 2021), one patient achieved complete response, nine achieved partial response, and 11 achieved stable disease, with an ORR of 40% (95% CI 21-61%) and DCR of 84% (95% CI 64-95%). The median PFS was 9.0 (95% CI 5.4-12.6) months. The median OS was 24.0 (95% CI 8.2-39.8) months. All patients reported treatment-related adverse events (TRAEs). Grade 3 TRAEs occurred 26 times in 15 patients. No grade 4 or 5 toxicities occurred. CONCLUSIONS: This is the first trial of apatinib for the treatment of TETs. Apatinib showed promising antitumor activity and the toxicities were tolerable and manageable.

Efficacy and safety of anlotinib with and without EGFR-TKIs or immunotherapy in the treatment of elder patients with non-small-cell lung cancer: a retrospective study.

BACKGROUND: Anlotinib is a multitarget tyrosine kinase inhibitor for treating patients with advanced non-small cell lung cancer (NSCLC). We aimed to assess the efficacy and safety of anlotinib in elder patients with advanced NSCLC. METHODS: Elder patients with advanced NSCLC who received anlotinib were enrolled. They were all age ≥ 65 years and with demonstrated records of EGFR gene status. All patients had received treatment with anlotinib or immune checkpoint inhibitors (ICIs)/EGFR-TKIs. The efficacy was evaluated according to the efficacy evaluation criteria for solid tumors (RECIST 1.1). Common Adverse Events Evaluation Criteria (CTCAE 4.03) were used to evaluate adverse drug reactions. RESULTS: A total of 91 patients were included in this study. We divided the patients into two groups (EGFR wild type: 60 patients; EGFR mutation: 31 patients). Among EGFR negative patients, the progression-free survival (PFS) for anlotinib monotherapy and anlotinib combination ICI therapy was 3.2 months and 5.0 months, respectively (P = 0.012). The difference in overall survival (OS) between monotherapy and combination therapy was also significant (9.5 vs. 18.4 months, respectively P = 0.010). Interestingly, we further analyzed differences between patients with hypertension and without hypertension, and found that hypertension was associated with better prognosis (5.7 vs. 1.4 months, P < 0.0001). In the EGFR mutation group, the PFS for anlotinib and EGFR-TKI combination treatment indicated better efficacy than that of anlotinib monotherapy (1.83 months vs. 7.03 months, respectively, P = 0.001). The median OS for monotherapy and combination therapy in the EGFR mutation group showed no statistical difference (28.34 months vs. 31.37 months, P = 0.223). The most common adverse reactions were hypertension, fatigue, and hand-foot syndrome, mainly of grade 1 or 2. No significant increase in adverse reactions was observed in patients ≥ 70 years of age. CONCLUSIONS: Anlotinib treatment and combination regimens resulted in good efficacy and controllable adverse reactions in elder patients with advanced NSCLC.

Efficacy and safety of maintenance immune checkpoint inhibitors with or without pemetrexed in advanced non-squamous non-small cell lung cancer: a retrospective study.

BACKGROUND: Advanced non-squamous non-small cell lung cancer (NS-NSCLC) patients without driver gene mutations are usually treated with immune checkpoint inhibitors (ICIs) plus pemetrexed as maintenance therapy after first-line ICIs plus 4-6 cycles of pemetrexed/platinum. Some patients in the real world receive ICIs monotherapy as maintenance therapy. No clinical study has compared the efficacy and safety of ICIs with or without pemetrexed as maintenance therapy. METHODS: We performed a retrospective study analyzing clinical data of patients with NS-NSCLC who were diagnosed in Zhejiang Cancer Hospital from September 2018 to May 2021 and received maintenance therapy after 4-6 cycles of ICIs plus pemetrexed/platinum. Patients were divided into ICIs plus pemetrexed group and ICIs monotherapy group. Progression Free Survival 1 (PFS1) and PFS2, defined as the interval from the date of initial treatment and maintenance therapy to the date of systemic progression/death or the last follow-up, respectively. RESULTS: A total of 120 patients received ICIs with or without pemetrexed as maintenance therapy. Eighty-two patients received ICIs plus pemetrexed as maintenance therapy, and 38 patients received ICIs monotherapy. There were no statistically significant difference in median PFS1 between the ICIs monotherapy group and ICIs plus pemetrexed group (12.00 months vs. 12.07 months, P = 0.979). Among patients with PD-L1 TPS < 1%, the median PFS1 was worse with ICIs monotherapy (9.50 months vs. 14.20 months, P = 0.039). Among patients with PD-L1 TPS ≥50% or 1-49%, the median PFS1 in both groups was not statistically significant (P = 0.866, P = 0.589, respectively). Results for median PFS2 were similar to median PFS1, with statistically significantly different only in patients with PD-L1 TPS < 1% (P = 0.008). The 2-year survival rates of the two groups were similar (66.7% vs. 69.5%, P = 0.812). The incidence of fatigue was significantly higher in the ICIs plus pemetrexed group (P = 0.023). CONCLUSIONS: ICIs with or without pemetrexed can be used as maintenance therapy after first-line ICIs plus 4-6 cycles of pemetrexed/platinum in patients with advanced NS-NSCLC based on PD-L1 expression.

Treatment outcomes and prognosis of patients with primary and acquired BRAF-mutated non-small cell lung cancer: A multicenter retrospective study.

The incidence of primary and acquired BRAF mutations is low in non-small cell lung cancer (NSCLC), with limited demographic and treatment outcome data available for this patient population. We evaluated lung cancer samples with programmed cell death ligand 1 (PD-L1) information extracted from 12 051 cases (cohort A) of lung cancer from OncoPanscan™-based sequencing of tissue (Genetron Health) and conducted retrospective multicenter data analysis using the database of Zhejiang Cancer Hospital and four other centers (cohort B, including 73 primary BRAF mutation and 14 acquired BRAF mutation cases) to compare treatment outcomes of patient groups with primary and acquired BRAF mutations. In cohort A, after propensity score analysis, 165 samples of NSCLC with BRAF mutations were screened along with 165 paired non-BRAF mutation samples. We observed no significant differences in the proportion of samples with ≥1% PD-L1 between BRAF and non-BRAF mutant groups. The median progression-free survival (mPFS) period in 13 patients with primary BRAF mutations receiving BRAF tyrosine kinase inhibitors (BRAF-TKIs) was 7.0 months. The group with primary BRAF mutations receiving immune checkpoint inhibitor (ICI) combination chemotherapy had better PFS than those administered ICI monotherapy (14.77 months vs. 5.0 months, p = 0.025) and similar results were obtained for OS (unreached vs. 20.3 months, p = 0.013). For acquired BRAF mutations, mPFS of BRAF-TKI, ICI-based, and chemotherapy-based regimens were 3.8, 1.5, and 1.9 months, respectively. Therefore, for patients with the primary BRAF V600E mutation, targeted therapy or immunochemotherapy could serve as effective treatment choices, while for those with acquired BRAF V600E, targeted drug therapy may remain the preferred solution in China.

Clinical significance of Osaka prognostic score based on nutritional and inflammatory status in patients with esophageal squamous cell carcinoma.

BACKGROUND: It has been reported that Osaka prognostic score (OPS), based on C-reactive protein (CRP), total lymphocyte counts (TLC) and albumin (ALB), was relevant to prognosis in colorectal cancer. However, the role of OPS regarding prognosis in patients with esophageal squamous cell carcinoma (ESCC) has not been reported. The current study aimed to explore the clinical outcome of OPS and establish and validate a nomogram for survival prediction in ESCC after radical resection. METHODS: This retrospective study included 395 consecutive ESCC patients with radical resection. Then patients were randomly divided into two cohorts: training cohort (276) and validation cohort (119). The OPS, based on TLC, CRP and ALB, was constructed to verify the prognostic value by Kaplan-Meier curves and Cox analyses. A nomogram model for prognosis prediction of cancer-specific survival (CSS) was developed and validated in two cohorts. RESULTS: Kaplan-Meier curves regarding the 5-year CSS for the groups of OPS 0, 1, 2 and 3 were 55.3, 30.6, 17.3 and 6.7% (P < 0.001) in the training cohort and 52.6, 33.3, 15.8 and 9.1% (P < 0.001) in the validation cohort, respectively. Then the OPS score in multivariate Cox analysis was confirmed to be a useful independent score. Finally, a predictive OPS-based nomogram was developed and validated with a C-index of 0.68 in the training cohort and 0.67 in the validation cohort, respectively. All above results indicated that the OPS-based nomogram can accurately and effectively predict survival in ESCC after radical resection. CONCLUSION: The OPS serves as a novel, convenient and effective predictor in ESCC after radical resection. The OPS-based nomogram has potential independent prognostic value, which can accurately and effectively predict individual CSS in ESCC after radical resection.

The prognostic impact of mild and severe immune-related adverse events in non-small cell lung cancer treated with immune checkpoint inhibitors: a multicenter retrospective study.

Patients treated with immune checkpoint inhibitors (ICIs) often experience unique immune-related adverse events (irAEs), and the previous studies demonstrated an association between irAEs and better outcomes in patients with ICI treatment for advanced non-small cell lung cancer (NSCLC). However, the correlation between the occurrence of mild and severe irAEs and prognosis remains unclear. Additionally, little is known regarding the association between the timing of mild and severe irAEs and clinical outcomes. We retrospectively conducted a multicenter study of advanced NSCLC patients treated with ICI monotherapy. Of the 222 patients, 79 patients (35.6%) experienced at least one irAE, and most were of grade 1 or 2 (mild) (26.6%). The most common irAEs were pneumonitis (n = 21, 9.5%) and skin-related adverse reactions (n = 19, 8.6%). The median progression-free survival of all patients treated with ICIs was 3.2 months. Patients experiencing irAEs had a better prognosis than those without such events (6.5 vs. 2.6 months, p = 0.004), and mild irAEs were associated with the best prognosis. The difference in overall survival between mild and severe irAEs was significant (34.3 vs. 17.3 months, p = 0.021). We further analyzed differences between patients with irAEs occurring at 3 or 6 weeks, and found that the earlier the occurrence of mild irAEs, the better the prognosis; however, the opposite was true for severe irAEs. In summary, patients with early occurring mild irAEs showed better clinical outcomes, whereas those with early severe irAEs tended to show poorer clinical outcomes.

Immune checkpoint inhibitor-related adverse events in lung cancer: Real-world incidence and management practices of 1905 patients in China.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are the standard treatment for advanced lung cancer, but immune-related adverse events (irAEs) remain poorly understood, especially in a real-world setting. METHODS: A multicenter observational study was conducted. Medical records of lung cancer patients treated with ICIs at 26 hospitals from January 1, 2015, to February 28, 2021, were retrieved. Types of ICIs included antiprogrammed cell death 1 or antiprogrammed cell death ligand 1 (PD-L1) monotherapy, anticytotoxic T-lymphocyte antigen-4 monotherapy, or combination therapy. RESULTS: In total, 1905 patients with advanced lung cancer were evaluated. The median age was 63 (range 28-87) years, and the male/female ratio was 3.1:1 (1442/463). The primary histological subtype was adenocarcinoma (915). A total of 26.9% (512/1905) of the patients developed 671 irAEs, and 5.8% (110/1905) developed 120 grade 3-5 irAEs. Median duration from ICI initiation to irAEs onset was 56 (range 0-1160) days. The most common irAEs were thyroid dysfunction (7.2%, 138/1905), pneumonitis (6.5%, 124/1905), and dermatological toxicities (6.0%, 115/1905). A total of 162 irAEs were treated with steroids and 11 irAEs led to death. Patients with positive PD-L1 expression (≥1%) and who received first-line ICI treatment developed more irAEs. Patients who developed irAEs had a better disease control rate (DCR, 71.3% [365/512] vs. 56.0% [780/1145]; p < 0.001). CONCLUSIONS: The incidence rate of irAEs was 26.9% in a real-world setting. IrAEs might be related to a better DCR, but clinicians should be more aware of irAE recognition and management in clinical practice.

Prognostic Value of the Lung Immune Prognostic Index May Differ in Patients Treated With Immune Checkpoint Inhibitor Monotherapy or Combined With Chemotherapy for Non-small Cell Lung Cancer.

BACKGROUND: Lung immune prognostic index (LIPI) status was recently developed to predict responses to immune checkpoint inhibitor (ICI) treatments. However, it is unclear whether LIPI is a prognostic index for both patients treated with ICI monotherapy and patients treated with ICIs combined with chemotherapy (ICIs CC). METHODS: This retrospective study established the patterns of LIPI in Chinese patients with advanced non-small cell lung cancer. Lung immune prognostic index based on the derived neutrophil-to-lymphocyte ratio greater than 3 and lactate dehydrogenase greater than the upper limit of normal was developed to characterize good, intermediate, or poor LIPI status. Associations between LIPI status and progression-free survival (PFS) and overall survival (OS) were analyzed. Kaplan-Meier curves and Cox proportional hazards models were used to determine survival differences. RESULTS: Three hundred thirty patients were included in this study. Of these patients, 216 received ICI monotherapy and 114 received ICIs CC. A good LIPI status was associated with better PFS (6.1 months vs. 2.3 months vs. 2.1 months, P = 0.023) and OS (24.2 months vs. 14.5 months vs. 9.3 months, P < 0.001) in ICI monotherapy compared to intermediate or poor LIPI status. No differences in PFS (17.9 vs. 9.9 months vs. 7.6 months, P = 0.355, respectively) and OS (P = 0.346) were observed in patients who received ICIs CC. Moreover, we found that patients who had an improved LIPI status compared with the baseline value had a longer PFS with ICI monotherapy and LIPI intermediate status (8.4 months vs. 2.1 months vs. 1.4 months, P < 0.001). However, in patients treated with ICIs CC, these dynamic changes were not observed (P = 0.444). CONCLUSIONS: Lung immune prognostic index status and dynamic changes in LIPI could be prognostic markers of treatment response to ICI monotherapy, but not to ICIs CC. In particular, good LIPI status was associated with a better clinical outcome compared with intermediate and poor LIPI status in ICI monotherapy treatment.

Correction: Distinct co-acquired alterations and genomic evolution during TKI treatment in non-small-cell lung cancer patients with or without acquired T790M mutation.

The original version of this Article omitted the following from the Acknowledgements: Professor Stebbing sits on SABs for Celltrion, Singapore Biotech, Vor Biopharma, TLC Biopharmaceuticals and Benevolent AI, has consulted with Lansdowne partners, Vitruvian and Social Impact Capital and Chairs the Board of Directors for BB Biotech Healthcare Trust and Xerion Healthcare. This has now been corrected in both the PDF and HTML versions of the Article.

Distinct co-acquired alterations and genomic evolution during TKI treatment in non-small-cell lung cancer patients with or without acquired T790M mutation.

EGFR-mutant non-small-cell lung cancer (NSCLC) patients inevitably develop drug resistance when treated with EGFR tyrosine kinase inhibitors (TKIs). Systematic genetic analysis is important to understand drug-resistant mechanisms; however, the clinical significance of co-occurring genetic alterations at baseline, co-acquired mutations at progressive disease (PD), and the clonal evolution remain underinvestigated. We performed targeted sequencing of pre-treatment and PD tumor samples from 54 EGFR-mutant NSCLC patients. Ten additional patients were sequenced using whole-exome sequencing to infer the clonal evolution patterns. We observed a domain-dependent effect of PIK3CA mutation at baseline on patient progression-free survival (PFS). In addition, at baseline, 9q34.3/19p13.3 (NOTCH1/STK11/GNA11) showed a co-deletion pattern, which was associated with a significantly worse PFS (p = 0.00079). T790M-postive patients with other concurrent acquired oncogenic mutations had a significantly shorter PFS (p = 0.005). Besides acquired T790M mutation, chromosomal instability (CIN) related genes, including AURKA and TP53 alterations, were the most frequently acquired events. CIN significantly increased during TKI treatment in T790M-negative patients and is a candidate resistance mechanism to the first-generation TKIs. Clonal evolution analyses suggest that the composition and relationship among resistant subclones, particularly relationship with T790M subclone, affect patients' outcomes. Overall, our findings of novel co-occurring alterations and clonal evolution patterns can be served as predictive biomarkers to stratify patients and help to better understand the drug-resistant mechanism to TKIs.

Olanzapine with ondansetron and dexamethasone for the prevention of cisplatin-based chemotherapy-induced nausea and vomiting in lung cancer.

Olanzapine is an atypical antipsychotic that has shown efficacy for the treatment of nausea, anxiety, and insomnia. This study was conducted to evaluate the efficacy of olanzapine (5 mg) combined with 5-HT3 receptor antagonists and dexamethasone for the prevention of chemotherapy-induced nausea and vomiting (CINV) in lung patients receiving cisplatin-based (25 mg/m2 d1-3) highly emetogenic chemotherapy (HEC).Olanzapine (5 mg) was administered a day prior to cisplatin administration and continued on days 1 to 5. We evaluated complete response (CR) rate and rates of no nausea and no vomiting in 3 periods. In addition, Self-Rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS), and The Functional Living Index-Emesis (FLIE) questionnaire were also assessed.A total of 40 lung cancer patients were included. CR for acute, delayed, and over all phases were 82.5%, 75.0%, and 70.0%, respectively. The rate of no nausea in the acute phase was 70.0% and 62.5% in delayed phase. The rate of no vomiting in the acute phase was 85.0%, and 77.5% in delayed phase. The rate of no nausea and no vomiting in the overall phase were 57.5% and 75.0%, respectively. The median SAS and SDS score were 37.9 and 41.6 in pre-chemotherapy, respectively. Up to day 6 after chemotherapy treatment, the median SAS and SDS score were 36.9 and 42.0, respectively. The median FLIE score was 111.7. The main side effects were grade 1 somnolence (35.0%) and mild constipation (52.5%).Around 5 mg olanzapine may be used as a potential, safe, and cost-beneficial alternative to prevent nausea and vomiting for HEC, particular for multiday chemotherapy regimen.

Salvage treatment with apatinib for advanced non-small-cell lung cancer.

OBJECTIVE: No definitive chemotherapeutic regimen has been established in patients with non-small-cell lung cancer (NSCLC) who failed second- or third-line treatment. The aim of this study was to evaluate apatinib, a VEGFR-2 inhibitor, in advanced NSCLC as salvage treatment. METHODS: We evaluated the efficacy and toxicity of apatinib in patients with previously treated advanced NSCLC from 2014 to 2015 in Zhejiang Cancer Hospital. Survival analysis was performed by the Kaplan-Meier method. RESULTS: Forty-two patients were included in the present study. Four patients achieved partial response, and 22 achieved stable disease, representing a response rate of 9.5% and a disease control rate of 61.9%. Median progression-free survival and overall survival were 4.2 and 6.0 months, respectively. The toxicities associated with apatinib were generally acceptable with a total grade 3/4 toxicity of 50%. CONCLUSION: Apatinib appears to have some activity against advanced NSCLC when utilized as salvage treatment.

Molecular Profiling and Survival of Completely Resected Primary Pulmonary Neuroendocrine Carcinoma.

BACKGROUND: Currently, molecular profiles and prognosis of primary pulmonary neuroendocrine carcinoma (PNC) are poorly elucidated. The present study was designed to evaluate genomic abnormalities and survival in patients with primary PNC. METHODS: Completely resected PNC samples were collected from Zhejiang Cancer Hospital during the period of 2008 to 2015. Nine driver genes, including 6 mutations (EGFR, KRAS, NRAS, PIK3CA, BRAF, and HER2) and 3 fusions (ALK, ROS1, and RET), were evaluated by reverse transcription-polymerase chain reaction (RT-PCR). Survival analysis was conducted by the Kaplan-Meier method. RESULTS: A total of 108 patients with pathologically confirmed PNC were enrolled. The types were pulmonary large-cell neuroendocrine carcinoma (PLCNC, n = 52), small-cell lung cancer (SCLC, n = 44), and carcinoid (n = 12). Twelve patients (11.1%) harbored genomic aberrations. The most frequent gene abnormalities in decreasing order were PIK3CA (n = 5, 4.6%), EGFR (n = 3, 2.8%), KRAS (n = 2, 1.9%), ALK (n = 1, 0.9%), and RET (n = 1, 0.9%). No ROS1, BRAF, NRAS, or HER2 mutation was detected. The frequencies of gene aberrations were 15.4%, 6.8%, and 8.3% in PLCNC, SCLC, and carcinoid, respectively. Survival differences existed among PLCNC, SCLC, and carcinoid groups (37.0 vs. 34.0 vs. not reached, P = .035); however, no difference existed between PLCNC and SCLC groups (P = .606). CONCLUSIONS: Genomic abnormality is rare in patients with PNC and it is the most frequently observed in PLCNC.

Mutational profiling of non-small-cell lung cancer patients resistant to first-generation EGFR tyrosine kinase inhibitors using next generation sequencing.

Patients with advanced non-small-cell lung cancer (NSCLC) harboring sensitive epithelial growth factor receptor (EGFR) mutations invariably develop acquired resistance to EGFR tyrosine kinase inhibitors (TKIs). Identification of actionable genetic alterations conferring drug-resistance can be helpful for guiding the subsequent treatment decision. One of the major resistant mechanisms is secondary EGFR-T790M mutation. Other mechanisms, such as HER2 and MET amplifications, and PIK3CA mutations, were also reported. However, the mechanisms in the remaining patients are still unknown. In this study, we performed mutational profiling in a cohort of 83 NSCLC patients with TKI-sensitizing EGFR mutations at diagnosis and acquired resistance to three different first-generation EGFR TKIs using targeted next generation sequencing (NGS) of 416 cancer-related genes. In total, we identified 322 genetic alterations with a median of 3 mutations per patient. 61% of patients still exhibit TKI-sensitizing EGFR mutations, and 36% of patients acquired EGFR-T790M. Besides other known resistance mechanisms, we identified TET2 mutations in 12% of patients. Interestingly, we also observed SOX2 amplification in EGFR-T790M negative patients, which are restricted to Icotinib treatment resistance, a drug widely used in Chinese NSCLC patients. Our study uncovered mutational profiles of NSCLC patients with first-generation EGFR TKIs resistance with potential therapeutic implications.

[Efficacy of crizotinib for 28 cases of advanced ALK-positive non-small cell lung cancer].

OBJECTIVE: This study aims to evaluate the efficacy and safety of crizotinib for advanced ALK-positive non-small cell lung cancer (NSCLC) patients. METHODS: Twenty-eight patients with advanced ALK-positive NSCLC were given orally crizotinib 250 mg b. i.d., and were followed up to evaluate the therapeutic efficacy and safety. RESULTS: Among the 28 patients, the objective response rate (ORR) was 71.4% (20/28) and disease control rate (DCR) was 92.9% (26/28). Three patients achieved complete response. Seventeen patients had partial response. The most common drug-related adverse events were mild flickering vision and gastrointestinal reaction. Eleven patients experienced flickering vision. Nine patients had nausea and vomiting. Eight patients had diarrhea. They were all reversible and of grade I or II. Only one patient had grade III myelosuppression. Among the 28 patients, 16 cases were disease-free and 12 cases had progressive disease, with a progression-free survival of 8.2 months. CONCLUSIONS: Crizotinib is effective and tolerable in the treatment of advanced ALK-positive NSLCC. However, its long-term treatment efficacy requires to be further studied.

Association between polymorphisms in CHRNA3 and PHACTR2 gene and environment and NSCLC risk in Chinese population.

Aims. This study aimed to investigate CHRNA3 (rs8040868) and PHACTR2 (rs9390123) single-nucleotide polymorphisms (SNPs) for association with non-small-cell lung cancer (NSCLC) risk in a Chinese population, and whether the environment affects the genetic polymorphisms. Methods. This case and control study included 500 NSCLC patients and 500 age-matched healthy controls. CHRNA3 (rs8040868) and PHACTR2 (rs9390123) SNPs were genotyped and associated for NSCLC risk by computing the odds ratio and 95% confidence interval from multivariate unconditional logistic regression analyses with adjustment of age. Results. The minor allele frequency (MAF) of CHRNA3 (rs8040868) and PHACTR2 (rs9390123) was 0.350 (C) and 0.397 (C), respectively. The frequencies of genotype and allele in CHRNA3 (rs8040868) and PHACTR2 (rs9390123) were not significantly different between the cases and controls, or between either of the subgroups. Conclusion. Although rs8040868 and rs9390123 SNPs are not associated with NSCLC risk in Chinese population, the results strongly suggest that geographical agents interact with human genetic polymorphism independent of ethnic background.