Anti-angiogenic therapy or immunotherapy? A real-world study of patients with advanced non-small cell lung cancer with EGFR/HER2 exon 20 insertion mutations.

Background: For patients with EGFR/HER2 exon20 insertions, platinum-containing double-drug chemotherapy is still the standard treatment method. First-generation TKIs have almost no therapeutic activity against EGFR exon 20 insertions. The efficacy of second-and third-generation TKIs is still controversial. Immunotherapy research is scarce, and there is an urgent need for more evidence and new treatment options for this group of patients. Methods: We reviewed patients with advanced NSCLC with EGFR/HER2 exon 20 insertion mutations treated in Shanghai Chest Hospital and Shanghai Pulmonary Hospital from 2015 to 2022 and assessed the efficacy of receiving chemotherapy, anti-angiogenic therapy and immunotherapy, including objective response rate (ORR) and disease control rate (DCR), and compared progression-free survival (PFS) and overall survival (OS). Results: Of the 126 patients included in the study, 51 patients had EGFR20ins mutations and 7 5 patients had HER2-20ins mutations. In the first-line treatment, bevacizumab + chemotherapy (Beva+Chemo), ICI+chemotherapy (ICI+Chemo), compared with chemotherapy alone (Chemo), ORR: 40% vs 33.3% vs 15% (p=0.0168); DCR: 84% vs 80.9% vs 67.5% (p=0.1817); median PFS: 8.3 vs 7.0 vs 4.6 months (p=0.0032), ICI+Chemo has a trend of benefiting on OS. Stratified analysis showed that compared with chemotherapy, ICI+Chemo was more effective for EGFR20ins mutation with median PFS: 10.3 vs. 6.3m (P=0.013); Beva+Chemo was more effective for HER2-20ins mutation, with a median PFS: 6.6 vs. 4.3m (p=0.030). In the second-line treatment of EGFR20ins mutation, bevacizumab + chemotherapy has a significant advantage in PFS compared with targeted therapy, median PFS:10.8 vs 4.0 months (P=0.016). Conclusion: For patients with EGFR20ins mutation, compared to chemotherapy, ICI+Chemo prolongs PFS, and after chemotherapy progression, bevacizumab combined with chemotherapy seems better than Furmonertinib-based targeted therapy on PFS. For HER2-20ins mutation, Beva+Chemo may be a better choice.

Special issue "The advance of solid tumor research in China": Real-world clinical outcomes of alectinib for advanced nonsmall-cell lung cancer patients with ALK fusion in China.

Global phase 3 trials have demonstrated the priority of several next-generation anaplastic lymphoma kinase-tyrosine kinase inhibitors (ALK-TKIs). However, clinical studies are conducted with specific populations that differ from the real world. The study aimed to evaluate the clinical outcomes of alectinib in real-world settings. Patients with advanced nonsmall-cell lung cancer (NSCLC) and EML4-ALK fusion were enrolled from two medical centers between June 2018 and June 2020. The primary endpoints were objective response rate (ORR) and progression-free survival (PFS) to alectinib. The secondary endpoint was response of brain metastases. The risk factors for disease progression were also investigated. In total, 127 patients with advanced NSCLC were enrolled into this study. Of them, 54.3% received first-line alectinib. The 1- and 2-year PFS rates were 77.4% and 68.3%, respectively. ORR and disease control rate (DCR) were 53.5% and 91.3%, respectively. Among patients with brain metastases, intracranial ORR and DCR were 63.6% and 88.6%, respectively. In addition, we found that "crizotinib pretreatment", "liver metastasis" and "TP53 co-mutation" were individually associated with shorter PFS in alectinib treatment. In conclusion, this study confirms the salient clinical outcomes of alectinib for ALK-fusion-driven NSCLC patients with or without brain metastases, adding real-world evidence to the priority of alectinib in clinical practice.

Comparison of the efficacy and safety in the treatment strategies between chemotherapy combined with antiangiogenic and with immune checkpoint inhibitors in advanced non-small cell lung cancer patients with negative PD-L1 expression: A network meta-analysis.

Background: In the first-line treatment of advanced non-small cell lung cancer (NSCLC), for those patients with negative PD-L1 expression, which treatment strategy has the better efficacy and safety between chemotherapy combined with antiangiogenic and with immune checkpoint inhibitors (ICIs) is still unclear due to the absence of head-to-head clinical trials. This study aims to answer the question by performing a systematic review and network meta-analysis (NMA). Methods: Electronic databases (PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov) were systematically searched accordingly to extract eligible studies from inception to October 2022, as well as the abstracts from the most recent main oncology congresses (American Association for Cancer Research (AACR), American Society of Clinical Oncology (ASCO), World Conference on Lung Cancer (WCLC), and European Society for Medical Oncology (ESMO)). Overall survival (OS), progression-free survival (PFS), and adverse events (AEs) of grades 3 to 5 were independently extracted and collected by two reviewers based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. We used Cochrane's risk of bias tool for randomized controlled trials through RevMan 5.3 to ascertain the quality of the included studies. NMA with a Bayesian random-effects model was performed by R (version 4.0.4). Results: According to the ranking list from OS-NMA, pembrolizumab combined with chemotherapy has the most effective ranking first (surface under the cumulative ranking (SUCRA) = 0.809844) (pooled HR = 0.65 [0.51-0.83]). On PFS, the triple combination of nivolumab/bevacizumab/chemotherapy ranks first (NMA estimate: HR = 0.35 [0.28-0.43]). On safety, in combination with chemotherapy, sintilimab has minimal toxicity, followed by pembrolizumab+chemo. Conclusions: In advanced NSCLC patients with negative PD-L1 expression, pembrolizumab+chemo ranks first in the efficacy of OS and does not apparently increase the incidence of any grade ≥ 3 AE as compared with chemo alone. On PFS, pembrolizumab also has advantages, but for patients with squamous cell carcinoma, camrelizumab+chemo seems to be a better choice. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42021231441.

A retrospective study for prognostic significance of type II diabetes mellitus and hemoglobin A1c levels in non-small cell lung cancer patients treated with pembrolizumab.

Background: Diabetes mellitus (DM) is common and recognized as a risk factor for developing non-small cell lung cancer (NSCLC) while the prognostic evaluation is still controversial. As immunotherapy is widely used in clinical practice, its efficacy and survival should be investigated in patients with DM. Methods: We retrospectively recruited 266 locally advanced and metastatic NSCLC patients who received pembrolizumab alone or in combination with chemotherapy. Patients' clinicopathological data, including age, history of DM, hemoglobin A1c (HbA1c), genetic tumor profiling, and survival data were collected. Associations between clinical characteristics and survival were evaluated by univariate and multivariate analyses. Results: In this cohort, 15.04% (40/266) of the patients had a history of DM. Fifty-nine (22.2%) patients had a HbA1c level ≥6.5%. A total of 169 (63.5%) patients received 1st-line therapy, and 97 (36.5%) received 2nd- or subsequent-line therapy. Patients with high (≥6.5%) HbA1c and lower (<35 g/L) albumin levels at baseline had worse survivals, and epidermal growth factor receptor (EGFR) mutants significantly associated with worse outcomes at normal HbA1c (<6.5%) levels (all P<0.05). Among the 1st-line therapy patients, a higher HbA1c level (≥6.5%) at baseline indicated a worse overall survival (OS) (2-year survival rate: 31.25% vs. 27.03%, P=0.045), tumor protein p53 (TP53) alternations and high programmed death-ligand 1 (PD-L1) expression (≥50%) were significantly associated with better outcomes (P<0.05). For 2nd- or subsequent-line patients, EGFR mutants and non-squamous carcinomas (non-SCs) indicated worse survivals, and the normal peripheral blood markers of the carcinoembryonic antigen (CEA), C-reactive protein (CRP), albumin levels were favorable prognostic factors for survivals. In non-SCs, Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations, high PD-L1 expression, and normal alkaline phosphatase (ALP) levels favored better progression-free survival (PFS), while EGFR mutants indicated poor PFS (P<0.05). Conclusions: Among patients treated with 1st-line immunotherapy, a higher HbA1c level (≥6.5%) indicated dismal OS, while history of DM, baseline blood glucose levels, and glucose changes during the treatment process were not significantly associated with any of the outcomes.

Effective low-dose Anlotinib induces long-term tumor vascular normalization and improves anti-PD-1 therapy.

Anlotinib is a new multitarget tyrosine kinase inhibitor for tumor angiogenesis, and its monotherapy exhibits a decent clinical efficacy. However, the process of combining Anlotinib and immune checkpoint therapy to achieve optimal antitumor effects while limiting side effects remains unclear. In this study, we found that effective low-dose Anlotinib was sufficient to inhibit tumor growth while reducing side effects compared with high doses. Effective low-dose Anlotinib treatments induced durable tumor vascular normalization and improved anti-PD-1 therapy in both short- and long-term treatment regimens. Mechanistically, the combination therapy increased the proportions of intratumoral CD4+ T, CD8+ T, and NK cells. Anlotinib-associated antitumor effects were independent of interferon γ; however, the combination therapy required CD8+ T cells to suppress tumor growth. Together, these results suggest that the combination of effective low-dose Anlotinib and PD-1 blockade induces durable antitumor effects with fewer side effects. Our findings indicate that antiangiogenic treatments combined with immune checkpoint therapy at an effective low-dose, rather than a tolerable high dose, would be more efficacious and safer.

Pembrolizumab monotherapy or combination therapy for bone metastases in advanced non-small cell lung cancer: a real-world retrospective study.

BACKGROUND: The incidence of bone metastases in non-small cell lung cancer (NSCLC) patients is about 30-40% and bone-related events can seriously affect quality of life. Immune checkpoint inhibitor (ICI) therapy has become the standard treatment for advanced NSCLC patients. However, the specific efficacy of ICIs in NSCLC patients with bone metastases remains unclear. The aim of the present study was to explore the prognosis of immunotherapy in this population and to find potential biomarkers. METHODS: In this retrospective study, a total of 110 advanced NSCLC patients with bone metastases who received pembrolizumab therapy were enrolled. Patient characteristics; palliative bone radiotherapy or bone-targeted therapy; serum levels of lactate dehydrogenase (LDH), and the neutrophil-to-lymphocyte ratio (NLR) at baseline were assessed. The correlation of these factors with progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) was analyzed. RESULTS: The ORR of the total population was 29.1%, and PFS and OS were 7.0 and 14.8 months, respectively. Fifty-eight patients (52.7%) received pembrolizumab treatment as first-line therapy, and 52 patients (47.3%) as second-line therapy or beyond [ORR: 41.4% vs. 15.4%, P=0.011; PFS: 9.0 vs. 4.0 months, P=0.004; OS: not reached (NR) vs. 11.5 months, P<0.0001]. Bone therapy, including palliative bone radiotherapy and bone-targeted therapy, increased the ORR (34.9% vs. 11.1%, P<0.0001) and prolonged PFS (8.5 vs. 2.0 months, P=0.002). Eastern Cooperative Oncology Group performance status score of 0-1 [OS: hazard ratio (HR) =0.117, P<0.0001] and first-line pembrolizumab therapy (OS: HR =0.372, P=0.004) were independent predictors of OS. Patients whose baseline serum LDH level was ≤240.5 IU/L (NR vs. 10.0 months, P<0.0001) or NLR ≤5.55 (NR vs. 18.0 months, P=0.039) showed longer OS. CONCLUSIONS: The efficacy of Pembrolizumab therapy is confirmed in advanced NSCLC patients with bone metastases, particularly when palliative bone radiotherapy or bone-targeted therapy is delivered. Baseline serum LDH level ≤240.5 IU/L and NLR ≤5.55 might predict the prognosis of patients with bone metastases from advanced NSCLC treated with immunotherapy.

Mining GEO and TCGA Database for Immune Microenvironment of Lung Squamous Cell Carcinoma Patients With or Without Chemotherapy.

BACKGROUND: Chemotherapy is the main treatment for patients with lung squamous cell carcinoma (LUSC). However, how chemotherapy affects their immune system is rarely reported. This study was aimed to compare the differences in the immune microenvironment of LUSC patients with or without chemotherapy. METHODS: A total of 494 LUSC samples were obtained from The Cancer Genome Atlas (TCGA) database. The immune cell infiltration was evaluated by the ssGSEA algorithm, and the tumor subtype was assayed by ConsensusClusterPlus. The differences in tumor mutation burden (TMB) and clinical information between the two types were then compared. Additionally, the differentially expressed genes (DEGs) between two types were analyzed and hub genes were validated in the GEO database. RESULTS: LSCC samples in TCGA were divided into three subtypes. Then, combining the tumor subtype and immune scores, the samples were divided into hot and cold tumors. Regardless of whether LUSC patients received chemotherapy, the survival of the hot tumor group was not significantly prolonged compared with that of the cold tumor group. For LUSC patients who received chemotherapy, the TMB value in hot tumor group was significantly higher. Total 501 DEGs were identified between two groups. The high expressions of hub genes CD19, CTLA4, FCGR3B, CD80, IL-10, etc. were also validated in the GSE37745 dataset. CONCLUSION: Chemotherapy does not affect the survival and prognosis of LUSC patients, but it significantly increases the TMB value of patients with hot tumor. The DEGs, especially hub genes, such as CD19, CTLA4, and FCGR3B, may serve as biomarkers to distinguish cold and hot tumors in LUSC.

Treatment efficacy of HER2-mutant lung adenocarcinoma by immune checkpoint inhibitors: a multicenter retrospective study.

BACKGROUND: Despite the remarkable clinical advance of immune checkpoint inhibitors (ICIs) in the treatment of lung cancer, there are limited studies focused on evaluating efficacy of ICIs for patients with human epidermal growth factor receptor 2 (HER2)-mutant lung adenocarcinoma. METHODS: We conducted a multicenter retrospective study of patients with HER2-mutant lung adenocarcinoma who received ICIs therapy at Shanghai Pulmonary Hospital, Shanghai Chest Hospital and the First Affiliated Hospital of Wenzhou Medical University between 2016 and 2021. Response was defined with reference to the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. RESULTS: Among the 26 patients enrolled in our study, the overall objective response rate (ORR) was 38.5%, disease control rate (DCR) was 84.6% and median progression-free survival (PFS) was 7.4 months. Majority of patients were treated with immunochemotherapy combination regimens (16/26, 61.5%), with a median PFS of 8.4 months. Among the 9 patients receiving ICIs-based therapy as first-line treatment, 5 patients had partial response (PR) and 4 patients had stable disease (SD), with a median PFS of 9.1 months. Of the entire cohort, 5 patients who received ICIs before epidermal growth factor receptor (EGFR)/HER2-targeting drugs achieved a median PFS of 8.4 months. CONCLUSION: Our retrospective study provides clinical evidence that front line of ICIs-based therapy is also worth considering for the treatment to improve survival outcomes of patients with HER2-mutant lung adenocarcinoma.

Epidermal Growth Factor Receptor Mutation Status and Response to Tyrosine Kinase Inhibitors in Advanced Chinese Female Lung Squamous Cell Carcinoma: A Retrospective Study.

BACKGROUND: The frequency of epidermal growth factor receptor (EGFR) mutations and the efficacy of tyrosine kinase inhibitor (TKI) in Chinese female patients with lung squamous cell carcinoma (SCC) are unknown. This study was designed to investigate the incidence of EGFR mutations and the role of targeted therapy in advanced Chinese female lung SCC patients. METHODS: Advanced female patients diagnosed with lung SCC at the Shanghai Chest Hospital between January 2013 and December 2018 were retrospectively analyzed. RESULTS: A total of 4223 advanced lung SCC patients were screened, and there were 154 female lung SCC patients who had underwent EGFR mutation detection. Positive EGFR mutations were found in 29.9% (46/154) of female lung SCC patients, including twenty-three 19del mutation (14.9%), twenty-one 21L858R mutation (13.6%) and other mutations (1.4%, 21861Q and 20ins). For 45 EGFR positive mutation female SCC patients, the median progression-free survival (PFS) of patients who received EGFR-TKI therapy (n=38) was 8.0 months (95% CI, 5.4-10.7 months), which was significantly longer than patients who were treated with chemotherapy (8.0 vs. 3.2 months, p=0.024), and the median overall survival (OS) was also longer (24.9 months vs. 13.9 months, p=0.020). The objective response rate (ORR) was 44.7% (17/38), and the disease control rate (DCR) was 81.6% (31/38). For 105 female SCC patients with EGFR negative mutation, the median OS was 18.6 months (95% CI, 14.2-22.9 months) and it was no different from that of EGFR positive mutation patients (18.6 vs. 22.8 months, p=0.377). CONCLUSION: For advanced Chinese female lung SCC patients with EGFR positive mutations, targeted therapy could confer longer PFS and OS than chemotherapy, but the survival was similar with patients who were negative EGFR mutations.

Phase 1b Study of Sintilimab Plus Anlotinib as First-line Therapy in Patients With Advanced NSCLC.

INTRODUCTION: Although the interaction between tumor immune microenvironment and angiogenesis has been well established, evidence supporting the chemo-free combination of immune checkpoint inhibitors plus antiangiogenic tyrosine kinase inhibitors in treatment-naive patients with advanced NSCLC is insufficient. This report provides the efficacy and safety of sintilimab combined with anlotinib as first-line therapy for advanced NSCLC from a phase 1b trial (NCT03628521). METHODS: Eligible patients who were treatment-naive and had unresectable stage IIIB/C or IV NSCLC without EGFR/ALK/ROS1 mutations received sintilimab (200 mg, day 1) and anlotinib (12 mg, day 1-14) every 3 weeks till disease progression or unacceptable toxicity. Baseline programmed death-ligand 1 expression and tumor mutation burden status was assessed in all patients. The primary end points were objective response rate and safety. RESULTS: A total of 22 patients received sintilimab and anlotinib. Median follow-up was 15.8 months (range: 8.3-19.3). Sixteen patients achieved confirmed partial response with an objective response rate of 72.7% (95% confidence interval [CI]: 49.8%-89.3%) and disease control rate of 100% (95% CI: 84.6%-100%). Median progression-free survival was 15 months (95% CI: 8.3 m, not reached), and the 12-month progression-free survival rate was 71.4% (95% CI: 47.2%-86.0%). The incidence rate of grade 3 or higher treatment-related adverse events was 54.5%, and grade 3 hypertension was predominant (two of 22, 9.1%). No grade 4 treatment-related adverse events were observed, and one case of grade 5 immune-related pneumonitis occurred. CONCLUSIONS: To the best of our knowledge, this is the first study that assessed an anti-programmed cell death protein 1 antibody combined with a multitarget antiangiogenic tyrosine kinase inhibitor in the frontline setting for patients with NSCLC. In view of its encouraging efficacy, durability, and safety profile, sintilimab plus anlotinib represents a novel chemotherapy-free regimen in this patient population.

EGFR Tyrosine Kinase Inhibitor (TKI) Combined With Concurrent or Sequential Chemotherapy for Patients With Advanced Lung Cancer and Gradual Progression After First-Line EGFR-TKI Therapy: A Randomized Controlled Study.

INTRODUCTION: Continuing tyrosine kinase inhibitor (TKI) therapy may be beneficial when patients with non-small-cell lung cancer and EGFR mutations experience gradual disease progression after initial EGFR-TKI treatment. We aimed to compare the efficacy of simultaneous EGFR-TKI and chemotherapy with that of sequential treatment after patients' disease gradually progressed after first-line EGFR-TKI treatment. PATIENTS AND METHODS: Patients with gradual progression who were EGFR-T790M mutation negative were randomly divided into two groups. In the concurrent group, patients were treated with pemetrexed plus cisplatin along with the same EGFR-TKI. In the sequential group, patients continued with EGFR-TKI until the disease progressed again, according to RECIST, then switched to chemotherapy. We evaluated the patients' progression-free survival (PFS) and overall survival times. RESULTS: Ninety-nine patients were enrolled: 49 in the concurrent group and 50 in the sequential group. The median PFS (mPFS) was 7.7 months (95% confidence interval [CI], 3.6-11.7) in the concurrent group and 5.7 months (95% CI, 3.5-7.9) in the sequential group (hazard ratio = 0.66; 95% CI, 0.44-1.00; P = .026), respectively. For the sequential group, the mPFS1 and mPFS2 were 1.8 months (95% CI, 1.4-2.3) and 3.8 months (95% CI, 3.1-4.5), respectively. The median overall survival of the concurrent group was longer than that of the sequential group (20.0 vs. 14.7 months; hazard ratio = 0.52; 95% CI, 0.32-0.85; P = .038). CONCLUSION: For patients with advanced non-small-cell lung cancer and gradual progression who are EGFR-T790M mutation negative after initial EGFR-TKI therapy, EGFR-TKI combined with chemotherapy confers longer PFS and overall survival than sequential EGFR-TKI and chemotherapy does.

Clinical characteristics and prognostic factors of surgically resected combined small cell lung cancer: a retrospective study.

OBJECTIVES: Small cell lung cancer (SCLC) is the most malignant lung cancer. Some of them are mixed with non-small cell lung cancer(NSCLC, Non SCLC),which are called combined small cell lung cancer (C-SCLC).Due to the difficulty of pathological diagnosis and the complexity of treatment, studies of C-SCLC have just been rising in recent years. This study is to evaluate the clinical and pathologic characteristics of C-SCLC. METHODS: Stage Ⅰ-Ⅲa C-SCLC patients who received radical R0 surgery between 2009-2018 in Shanghai Chest Hospital were enrolled. Clinical characteristics and prognosis were analyzed. RESULTS: Totally 181 patients were included, most of them were small cell combined with large cell neuroendocrine components(SCLC/LCNEC,58.0 %,N = 105),then with adenocarcinoma(SCLC/ADC:13.8 %,N = 25),and finally with squamous cell carcinoma(SCLC/SCC:13.3 %,N = 24).Median DFS and OS of C-SCLC patients underwent radical surgery were 32.5 and 49.7 months.1,3 and 5 years DFS rates of the entire cohort were 68.5 %,32.6 % and 16.0 %,respectively. Patients with SCLC/LCNEC had longer DFS (44.1 m vs. 20.4 m, p = 0.040) and longer OS trend (62.1 m vs. 33.2 m, p = 0.122).Groups of whether tumor invaded the pleura(p = 0.028 and p = 0.050),lymph node stage(p = 0.029 and p = 0.010) and the courses of adjuvant chemotherapy(p = 0.011 and p = 0.001) had statistical differences on DFS and OS. CONCLUSIONS: SCLC/LCNEC was the most common type of C-SCLC. Patients' DFS and OS were also longer than other combined types. Adjuvant chemotherapy for SCLC is still the main treatment for surgical C-SCLC. Further studies are needed to clarify the clinical characteristics and prognosis of C-SCLC.

New advances in antiangiogenic combination therapeutic strategies for advanced non-small cell lung cancer.

PURPOSE: Tumor growth relies on the sufficient blood supply and continuously requires new blood vessels to maintain, which lead to vascular abnormalities (Folkman, N Engl J Med 285:1182-1186, 1971). Antiangiogenic therapy has emerged with the goal of normalizing vasculature and tumor microenvironment (TME). Some antiangiogenic therapies combined with chemotherapy, targeted therapy or immunotherapy have been approved for clinical application. In this review, we summarize the recent advances of antiangiogenic combination therapeutic strategies in advanced NSCLC. METHODS: References of this review are searched through PubMed and EMBASE and the abstracts of cancer conferences. The ClinicalTrials.gov database was used for relative trials. RESULTS: Based on different mechanisms, antiangiogenic agents can be divided into monoclonal antibodies (mAbs), which mainly include bevacizumab and ramucirumab, and multi-target antiangiogenic tyrosine kinase inhibitors (TKIs) which include sunitinib, sorafenib, nintedanib, apatinib, anlotinib, fruquintinib, etc. In recent years, a number of large clinical studies have shown that antiangiogenic agents have conferred a significant overall survival (OS) benefit to patients with advanced non-small cell lung cancer (NSCLC). More and more evidences confirm that the combination of antiangiogenic agents with chemotherapy, targeted therapy and immunotherapy can improve the effect and prolong the survival of NSCLC patients. However, many problems about the application of antiangiogenic agents on advanced NSCLC patients still need to be explored. For example, the combination therapy of multi-target antiangiogenic agents is just beginning, and the biomarkers are not clear. CONCLUSIONS: Antiangiogenic agents can achieve therapeutic benefit in advanced NSCLC patients and the combination of chemotherapy, targeted therapy or immunotherapy can lead to synergistic effect. However, exploring the best combination therapy and efficacy-related biomarkers needs further study.

First-line pemetrexed/carboplatin or cisplatin/bevacizumab compared with paclitaxel/carboplatin/bevacizumab in patients with advanced non-squamous non-small cell lung cancer with wild-type driver genes: A real-world study in China.

BACKGROUND: The study was conducted to compare the effectiveness and safety of pemetrexed/carboplatin or cisplatin/bevacizumab (PemPBev) and paclitaxel/carboplatin/bevacizumab (PacCBev) as first-line therapy for advanced non-squamous non-small cell lung cancer (NS-NSCLC) patients with wild-type driver genes in a real-world setting. METHODS: We retrospectively collected the medical records of advanced NS-NSCLC patients with wild-type driver genes administered first-line PemPBev or PacCBev therapy at Shanghai Chest Hospital between January 2014 and June 2016, and analyzed the differences in survival outcomes, efficacy, and safety between PemPBev and PacCBev treatment. RESULTS: A total of 390 patients were included in our analysis: 249 in the PemPBev group and 141 in the PacCBev group. Patients administered PemPBev experienced significantly improved progression-free survival (PFS) and overall survival (OS) compared to those administered PacCBev (PFS 7.5 vs. 6.2 months, hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.53-0.84, P < 0.001; OS:18.6 vs. 16.0 months, HR 0.68, 95% CI 0.52-0.90, P = 0.002). The objective response rate (ORR) and disease control rate (DCR) were similar between the groups (ORR 21.7% vs. 30.5%, P = 0.053; DCR 69.1% vs. 67.4%, P = 0.728). There was no significant difference in the incidence of adverse events between the groups (64.7% vs. 68.8%; P = 0.407), but the incidence of peripheral neuropathy in the PacCBev group was higher than in the PemPBev group (7.8% vs. 2.4%; P = 0.012). CONCLUSION: Our study shows that for advanced NS-NSCLC patients with wild-type driver genes, first-line PemPBev might be a better treatment option compared to PacCBev.