IIIB-IV Non-small Cell Lung Cancer Research Articles

The proportion of tumour stroma predicts response to treatment of immune checkpoint inhibitor in combination with chemotherapy in patients with stage IIIB-IV non-small cell lung cancer.

Immunotherapy has brought a new era to cancer treatment, yet we lack dependable predictors for its effectiveness. This study explores the predictive significance of intratumour stroma proportion (iTSP) for treatment success and prognosis in non-small cell lung cancer (NSCLC) patients undergoing treatment with immune check-point inhibitors (ICIs) together with chemotherapy. We retrospectively collected data from patients with unresectable stage IIIB-IV NSCLC who were treated with first-line ICIs and chemotherapy. Each patient received a confirmed pathological diagnosis, and the pathologist evaluated the iTSP on haematoxylin and eosin (H&E)-stained sections of diagnostic tissue slides. Among the 102 H&E-stained biopsy samples, 61 (59.8%) were categorised as stroma-L (less than 50% iTSP), while 41 (40.2%) were classified as stroma-H (more than 50% iTSP). We observed that the stroma-L group exhibited a significantly better objective response rate (ORR) (72.1 versus 51.2%, P = 0.031) and deeper response depth (DpR) (-50.49 ± 28.79% versus -35.83 ± 29.91%, P = 0.015) compared to the stroma-H group. Furthermore, the stroma-L group showed longer median progression-free survival (PFS) (9.6 versus 6.0 months, P = 0.011) and overall survival (OS) (24.0 versus 12.2 months, P = 0.001) compared to the stroma-H group. Multivariate Cox proportional hazards regression analysis indicated that iTSP was a highly significant prognostic factor for both PFS [hazard ratio (HR) = 1.713; P = 0.030] and OS (HR = 2.225; P = 0.003). Our findings indicate that a lower iTSP corresponds to improved clinical outcomes and greater DpR in individuals with stage IIIB-IV NSCLC treated with first-line ICIs and chemotherapy. The iTSP could potentially serve as a predictive biomarker for ICIs therapy response.

THE INITIAL TREATMENT RESULTS OF 6 PATIENTS WITH NON-SMALL CELL LUNG CANCER WITH EGFR AND ALK CONCURRENT MUTATIONS, AT THE CENTRAL LUNG HOSPITAL

Purpose: Evaluate the initial treatment results of non-small cell lung cancer with EGFR and ALK concurrent mutations. Subjects and methods: A prospective study, non-controlled description, and longitudinal follow-up of 6 patients with stage IIIB-IV non-small cell lung cancer, with EGFR and ALK concurrent mutations, at the National Lung Hospital, from January 2022 to July 2023. Results: The average age of patients was 65.5 years, the male/female gender ratio was 5/1, and the proportion of patients who smoked was 83.3%. Patients were mainly admitted to the hospital due to symptoms of cough (100%), chest pain (50.0%), and dyspnea (33.3%); the majority of patients with stage IV cancer (83.3%); all patients had adenocarcinoma (100%). The average disease-free survival time was 11.36 months. The common unwanted effects were mainly skin rash (83.3%) and diarrhea (66.7%). Elevated liver enzymes and renal failure occurred in the group of patients using a combination of EGFR-TKIs and ALK-TKIs and were the reasons for discontinuation of ALK-TKIs.

11P Decreased monocyte-to-lymphocyte ratio was associated with satisfied outcomes of first-line PD-1 inhibitors plus chemotherapy in stage IIIB-IV non-small cell lung cancer

11P Decreased monocyte-to-lymphocyte ratio was associated with satisfied outcomes of first-line PD-1 inhibitors plus chemotherapy in stage IIIB-IV non-small cell lung cancer

Decreased monocyte-to-lymphocyte ratio was associated with satisfied outcomes of first-line PD-1 inhibitors plus chemotherapy in stage IIIB-IV non-small cell lung cancer.

Immune-checkpoint inhibitors (ICIs) combined with chemotherapy are more widely used than monotherapy and have shown better survival in patients with advanced non-small cell lung cancer (NSCLC) without oncogenic driver alterations. The monocyte-to-lymphocyte ratio (MLR) might predict the treatment outcomes of ICI therapy in advanced NSCLC patients but has not yet been investigated. In addition, the cutoff of MLR is controversial. Therefore, the present study aimed to explore the associations between changes in MLR at the initial stage of treatment and clinical outcomes in stage IIIB-IV NSCLC patients receiving first-line PD-1 inhibitor combined with chemotherapy. The present study included 139 stage IIIB-IV NSCLC patients treated with first-line PD-1 inhibitor combined with chemotherapy. The blood results were assessed 10 days before initiation of PD-1 inhibitor-based combination therapy (time point 1, baseline) and before the third cycle of combined therapy (time point 2). Compared to altered MLR, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) in baseline and in time point 2, patients were divided into decreased MLR/NLR/PLR and increased MLR/NLR/PLR groups. The objective response rate (ORR), progression-free survival (PFS), and the association with the changes in blood indicators were analyzed. A total of 48 patients were categorized in the decreased MLR group and 91 in the increased MLR group. Patients with decreased MLR had a significantly higher ORR in the univariate (P<0.001) and multivariate (P<0.001) Cox proportional hazards models. On the other hand, decreased MLR was significantly associated with prolonged PFS in the univariate (P=0.007) and multivariate (P=0.016) analyses. Next, 91 patients comprised the decreased NLR group and 48 as the increased NLR group. Patients with decreased NLR exhibited high ORR (P=0.001) and prolonged PFS in univariate analysis (P=0.033). Then, 64 patients comprised the decreased PLR group and 75 the increased PLR group. Decreased PLR was significantly associated with high ORR in univariate (P<0.001) and multivariate (P=0.017) analyses. The subgroup analyses showed that decreased MLR was significantly associated with satisfactory outcomes in patients with all PD-L1 expressions. Decreased MLR was associated with high ORR and long PFS and might have a potential predictive value in patients with stage IIIB-IV NSCLC treated with first-line PD-1 inhibitor combined with chemotherapy. In addition, changes in MLR might have predictive value in all PD-L1-expressing populations. Decreased NLR and PLR also showed improved survival, suggesting that changes in NLR and PLR may be complementary to predicting prognosis.

Long-term survival analysis of patients with stage IIIB-IV non-small cell lung cancer complicated by type 2 diabetes mellitus: A retrospective propensity score matching analysis.

This study aimed to determine the effect of type 2 diabetes mellitus (T2DM) on overall survival (OS) of patients with stage IIIB-IV non-small cell lung cancer (NSCLC). We retrospectively analyzed patients with stage IIIB-IV NSCLC from January 2015 to December 2018 in the Department of Oncology at the First Affiliated Hospital of Anhui University of Traditional Chinese Medicine. Kaplan-Meier plots, log-rank tests, and Cox proportional hazards regression models were used to describe the effect of T2DM on the OS of patients with stage IIIB-IV NSCLC. This study collected data on 76 patients with NSCLC and T2DM (group A) and 214 NSCLC patients without T2DM (group B). After propensity score matching (PSM) analysis, 74 patients were included in each group. The mean OS of all patients was 17 months (range, 11-31 months). The mean OS of group A was 15 months (range, 8-25 months) and the mean OS of group B was 20 months (range, 14-39 months). The mean OS of group B was longer than group A, and the difference was statistically significant. Univariate analysis of the clinical data showed that T2DM and complications were significantly correlated with the prognosis of patients with stage IIIB-IV NSCLC (p=0.003 and p=0.034). Multivariate Cox model analysis showed that T2DM and complications were independent prognostic factors for patients with stage IIIB-IV NSCLC (p=0.002 and p=0.024, respectively). Stage IIIB-IV NSCLC patients without T2DM have an increased OS compared to patients with stage IIIB-IV NSCLE and T2DM.

Platelet-to-lymphocyte and neutrophil-to-lymphocyte ratios are associated with the efficacy of immunotherapy in stage III/IV non-small cell lung cancer.

Peripheral serological indicators are novel markers associated with prognosis in multiple malignant tumors. In the present study, platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) were selected to construct a model that predicts long-term survival of patients with stage IIIB-IV non-small cell lung cancer (NSCLC) who received treatment with an anti-programmed cell death protein-1 (PD-1) monoclonal antibody. A total of 133 patients were eligible for the present retrospective study (January 2019-February 2021). The area under the receiver operating characteristic curve was used to compare the diagnostic value of PLR and NLR, and combined PLR and NLR. The objective response rate and disease control rate of each group were obtained and the differences were compared using the χ2 test. The prognostic value of these indicators was assessed using the Kaplan-Meier method. Cox regression analysis was used to evaluate risk factors associated with long-term survival. Statistically significant parameters were included in the nomogram. Based on the median PLR and NLR values, the patients were divided into high PLR (H-PLR) (PLR >200.00, 67 patients) and low PLR (L-PLR) (PLR ≤200.00, 66 patients), and high NLR (H-NLR) (NLR >3.56, 65 patients) and low NLR (L-NLR) (NLR ≤3.56, 68 patients) groups. Immune-related adverse events (irAEs) occurred in 22 patients (16.5%) during the observation period, including 18 grade 2–3 irAEs and 4 grade 4 cases. H-NLR and H-PLR were associated with poor progression-free (PFS) and overall survival (OS) in the present study. NLR was an independent prognostic factor for PFS [hazard ratio (HR): 0.201, 95% confidence interval (CI): 0.060-0.670; P=0.009) and OS (HR: 0.413, 95% CI: 0.226-0.754; P=0.004) in this patient group. Therefore, NLR may be used in the prognostication of patients with stage IIIB-IV NSCLC treated with PD-1 inhibitors. These serological markers may be used in combination with established immunomarkers to help predict outcomes.

Elevated tumor markers for monitoring tumor response to immunotherapy

SummaryBackgroundAs the immune-related response evaluation criteria in solid tumors (irRECIST) by imaging greatly underestimated the objective response to immunotherapy, we established the response evaluation criteria in solid tumors based on tumor markers (RecistTM) to explore whether RecistTM can compensate for the deficiencies of the irRECIST criteria.MethodsThis was an observational study, which consisted of two parts. The first part (Group A) was a retrospective study including the patients with malignant solid tumors. The second part (Group B) was a prospective study, which were EGFR-negative and ALK-negative patients with stage IIIB-IV non-small cell lung cancer receiving first-line treatment. From January 2017 to September 2020, one hundred and ten patients with a three-time increase in tumor markers receiving immunotherapy were recruited. The treatment response to immunotherapy was evaluated by irRECIST and RecistTM. Efficacy, overall survival (OS), first evaluation time and earliest response time under the different evaluation criteria were compared by statistics.FindingsThe treatment response evaluated by the RecistTM criteria was not consistent with that evaluated by the irRECIST criteria (Kappa = 0.386, p < 0.001). RecistTM had a higher completed response (CR) rate compared to irRECIST criteria (20.9% vs 1.8%, p < 0.001). The earliest response time under the RecistTM criteria was 3.42 weeks earlier than that under the irRECIST criteria (u = -5.233, p < 0.001). There were significant differences in median OS between tumor marker-related complete response (tmCR) and tumor marker-related partial response (tmPR), as well as between tmPR and tumor marker-related stable disease (tmSD) (χ2 = 15.572, p < 0.001; χ2 = 7.720, p = 0.005), but not between tmSD and tumor marker-related progressive disease (tmPD) (χ2 = 1.596, p = 0.206). When applying both criteria together, for patients with immune-related CR / immune-related PR (irCR/irPR) (n = 54) under irRECIST criteria, there was a significant difference in median OS between achieving tmCR (n = 22) and tmPR (n = 32) (χ2 = 14.011, p < 0.001). RecistTM criteria can predict 1-year and 2-year OS more accurately than irRECIST criteria (AUCs:0.862 vs 0.552, 0.649 vs 0.521, respectively;both p < 0.001). In RecistTM, 4 patients had been observed with pseudoprogression in tumor markers.InterpretationThe RecistTM criteria could effectively distinguish CR, PR, and SD, which may help resolve the shortcomings of the RECIST criteria in evaluating the treatment response to immunotherapy, especially in assessing whether patients can achieve deep or even complete response as soon as possible.FundingThis work was supported by the Key projects of Chongqing Health and Family Planning Commission (to Xueqin Yang, 2019ZDXM011).

MA03.01 EPICAL Trial. A Phase Ib StudyCombining Anti-Epidermal Growth Factor (EGF) Vaccination With Afatinib in EGFR-Mutant Non-Small Cell Lung Cancer

Stage IIIB-IV non-small cell lung cancer patients with mutations in the EGF receptor gene (EGFR) usually derive clinical benefit from to tyrosine kinase inhibitors (EGFR TKIs) but ultimately relapse. In preclinical studies, we have showed that anti-EGF antibodies generated by vaccination significantly increased the antitumor activity of TKIs in EGFR-mut cell lines, blocking EGFR, Erk1/2, Akt and STAT3 activation and delaying emergence of resistance. Based on these findings, the EPICAL trial was initiated (ClinicalTrials.gov number, NCT03623750) .

Combined prognostic value of the SUVmax derived from FDG-PET and the lymphocyte-monocyte ratio in patients with stage IIIB-IV non-small cell lung cancer receiving chemotherapy

BackgroundWe evaluated the prognostic potential of tumor 18F-fluorodeoxyglucose (FDG) uptake derived from positron emission tomography (PET) and known inflammatory hematological markers, both individually and in combination, for chemosensitivity and survival in patients with stage IIIB-IV non-small cell lung cancer (NSCLC) receiving first-line chemotherapy.MethodsA total of 149 patients with stage IIIB and IV NSCLC (based on TNM 7th edition) were retrospectively reviewed. Maximum standardized uptake value (SUVmax) were used to quantitatively assess FDG uptake. The lymphocyte-monocyte ratio (LMR), neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) were selected as hematological markers. Receiver operating characteristic (ROC) curves were constructed for the determination of optimal cut-off values to predict chemotherapeutic response.ResultsPatients with SUVmax > 11.6 or LMR ≤3.73 exhibited a significantly lower objective response rate (ORR) to chemotherapy (p < 0.001 and p < 0.001). Through multivariable logistic regression analysis, both the SUVmax and LMR were identified as independent predictive factors for chemotherapeutic response (p = 0.001 and p < 0.001). Furthermore, a multivariable Cox proportional hazard model identified a high SUVmax (> 11.6) and low LMR (≤3.73) as independent predictors of poor PFS (p < 0.001 and p = 0.025) and OS (p < 0.001 and p = 0.032). A novel score system was constructed based on the SUVmax and LMR (SUV_LMR score), and patients were stratified into three subgroups. The patients with a score of 0 had a significantly higher ORR (88.9%) than did those with a score of 1 (59.6%) and score of 2 (25.0%) (p < 0.001). Moreover, multivariable Cox analysis further identified the SUV_LMR score as an independent prognostic factor for PFS (p < 0.001) and OS (p < 0.001).ConclusionsPre-treatment SUVmax and LMR were not only predictive factors for chemotherapeutic response but also independent prognostic factors of survival in stage IIIB-IV NSCLC. Moreover, the SUV_LMR score, which is based on primary tumor metabolic activity and the systemic inflammatory response, might provide a promising tool to predict chemosensitivity, recurrence and survival of advanced NSCLC.

A Clinical Study on Microwave Ablation in Combination with Chemotherapy in Treating Peripheral IIIB-IV Non-Small Cell Lung Cancer.

Background: This study investigated the efficacy and complications of microwave ablation in combination with chemotherapy in treating peripheral IIIB-IV non-small cell lung cancer (NSCLC). Materials and Methods: A total of 100 patients with peripheral IIIB-IV NSCLC were randomly divided into two groups: combination group (n = 52) and chemotherapy group (n = 48). Patients in the combination group were treated with microwave ablation, radiotherapy, and chemotherapy, whereas the patients in the chemotherapy group were treated with pemetrexed disodium or gemcitabine hydrochloride, cisplatin chemotherapy, and conventional radiotherapy. Results: The effectiveness and disease control rates were significantly higher in the combination group than in the chemotherapy group (p < 0.05). The second- and third-year survival rates were significantly higher in the combination group than in the chemotherapy group (p < 0.05). However, patients in the combination group had no serious complications, and there were no intraoperative and perioperative deaths. Conclusions: Microwave ablation is safe and effective. Combination chemotherapy is superior to chemotherapy in treating peripheral IIIB-IV NSCLC in terms of effectiveness rate, disease control rate, and extended patient survival time.

Real-world mutational profiling of Chinese non-small cell lung cancer patients with epidermal growth factor receptor (EGFR) uncommon mutations acquired resistant to icotinib using next generation sequencing: A multicenter study.

e21557 Background: Just like classical EGFR mutations, EGFR uncommon mutations non-small cell lung cancer (NSCLC) will still have acquired resistant problem to icotinib. The mechanism of icotinib resistance in such uncommon EGFR mutant patients has also risen to be a difficult question in lung cancer research. In order to explore the resistance mechanism in EGFR uncommon mutant NSCLC patients treated by icotinib, it is necessary to first identify the resistant gene profiles and clinic-pathologic characteristics of those patients. As far as we know that there is no large cohort of EGFR uncommon mutant NSCLC study in evaluating the efficacy and resistant genomic profiling of icotinib. Methods: We screened 3279 patients with NSCLC for EGFR uncommon mutations. Among them, 106 patients received icotinib treatment, and a total of 69 patients with stage IIIb-IV EGFR uncommon mutations NSCLC were undergoing tumor biopsies or blood withdrawing by the time of primary or acquiring to icotinib, in including formalin-fixed paraffin-embedded (FFPE) samples, serum samples and serous effusions. We used targeted next-generation sequencing to detect genes status of patients. Results: Among 69 patients treated with icotinib, 69.57% (48/69) developed acquired resistance, and 30.43% (21/69) had primary resistance. Using the specimens at the baseline, there were 39(81.25%) patients with EGFR T790M (including 7 patients with EGFR T790M, 32 patients with EGFR T790M plus EGFR amplification), 3(36.25%) patients with EGFR amplification, 1(2.08%) patient with BRAF mutation, 1(2.08%) patient with PIK3CA mutation, 1(2.08%) patient with CTNNB1 mutation, 1(2.08%) patient with ALK fusion, 1(2.08%) patient with ROS1 fusion, and 1(2.08%) patient with unknown status. Conclusions: EGFR T790M, EGFR amplification, BRAF mutation, PI3K-AKT-mTOR signaling pathway (PIK3CA mutations), CTNNB1 mutation, ALK fusion or ROS1 fusion might contribute to molecular mechanisms of acquired resistance to icotinib in EGFR uncommon mutations NSCLC. Our study uncovered EGFR uncommon mutational profiles of NSCLC patients with icotinib resistance with potential therapeutic implications.

The efficacy and safety of extended use of endostatin plus platinum-based doublet chemotherapy in patients with advanced non-small cell lung cancer: An analysis of a 10-year retrospective study.

e20523 Background: Endostatin is a potent inhibitor of angiogenesis developed and approved in China. We aimed to evaluated the efficacy and safety of extended use of endostatin with platinum-based chemotherapy for advanced non-small cell lung cancer (NSCLC) in this study. Methods: We performed a retrospective analysis of chemotherapy-naïve patient with stage IIIB-IV or recurrent NSCLC who had been treated with first-line chemotherapy plus endostatin between January 2008 and June 2018. The primary endpoints were progression-free survival (PFS) and overall survival (OS). The Cox proportional hazards regression model was used to assess the prognostic importance of risk factors (age, gender, smoking status, ECOG performance status, stage, histology, EGFR gene status and endostatin cycles). Results: A total of 105 patients were eligible for analysis. The median (range) cycles of chemotherapy with endostatin were 4 (2-19). The objective response rate and disease control rate were 45.1% and 87.3%, respectively. Under multivariate analysis, non-smoking status and extended use of endostatin (≥4 cycles) were significantly correlated with better PFS, and squamous cell cancer and extended use of endostatin (≥4 cycles) were significantly correlated with better OS. The median (95% CI) PFS and OS for patients with extended use of endostatin (≥4 cycles) or not were 8.2 (5.6-12.7) vs. 5.3 (2.8-7.3) months, HR = 0.63, p= 0.014, and 21.2 (6.8-37.7) vs. 11.9 (4.1-23.9) months, HR = 0.77, p= 0.028, respectively. Patients with squamous cell cancers significantly benefited from the extended use of endostatin (≥4 cycles) (n = 55, p= 0.043) but not adenocarcinoma (n = 46, p= 0.089). Hematologic and gastrointestinal toxicities occurred more frequently in patients who received extended use of endostatin (≥4 cycles), but no statistically significant difference was detected in those who did not. Conclusions: In patients with advanced/recurrent NSCLC, extended use of endostatin (≥4 cycles) could provide additional survival benefits and satisfactory toxicity profiles, especially for those with squamous cell cancer, which merits further evaluation in a larger prospective study.

1484P - Treatment patterns in patients (pts) with stage IIIB-IV non-small cell lung cancer (NSCLC) in Sweden: The SCAN-LEAF study

1484P - Treatment patterns in patients (pts) with stage IIIB-IV non-small cell lung cancer (NSCLC) in Sweden: The SCAN-LEAF study

Association between Charlson comorbidity index score and outcome in patients with stage IIIB-IV non-small cell lung cancer

BackgroundThis retrospective study investigated the association between the Charlson comorbidity index (CCI) score and the survival of patients with stage IIIB-IV (advanced, non-resectable) non-small cell lung cancer (NSCLC) who also did not have gene mutations in epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK).MethodsThe records of 165 patients (28–80 y, median 61 y) who met the above criteria and were admitted to Beijing Friendship Hospital Capital Medical University from 1 May 2010 to 1 October 2014were reviewed. Associations between baseline variables and the CCI score were assessed via univariate and multivariate logistic regression analysis. Overall survival was defined as the time from the first clinic visit to death from any cause, or to the end of follow-up. Survival curves were estimated via the Kaplan-Meier method and compared with the log-rank test.ResultsLogistic regression analyses indicated that smoking and performance status were independently associated with the CCI score. Smoking was associated with an increased risk of mortality (odds ratio (OR) 4.12 (95% confidence interval [CI] 1.92–8.84) compared to non-smokers), as was performance status 2 (ambulatory, capable of self-care, unable to perform any work activities; active for >50% of waking hours) (OR 2.22 (95% CI, 1.14–4.33) compared to performance status 1). Univariate Cox’s regression analyses showed that the hazard ratios were significantly associated with the CCI score (P = 0.009), smoking (P = 0.042), and male gender (P = 0.021).ConclusionThe CCI score is an important prognostic factor for the prediction of overall survival in patients with stage IIIB-IV NSCLC who are negative for EGFR and ALK gene mutations.

Effects of microwave ablation or its combination with whole-body chemotherapy on serum vascular endothelial growth factor levels in patients with stage IIIB/IV NSCLC.

We aimed to analyze the changes of serum vascular endothelial growth factor (VEGF) before and after microwave ablation (MWA) in patients with stage IIIB-IV non-small cell lung cancer (NSCLC), and to observe the effects of MWA combined with chemotherapy on short-term therapeutic efficacy and long-term survival. Concentrations of serum VEGF in 20 healthy subjects were considered as controls. Changes of serum VEGF were detected by ELISA before and after MWA (1 and 7 days after treatment). Seven days after MWA, patients were divided into a combination chemotherapy group of 22 subjects and a MWA alone group of 18 subjects. Serum VEGF was measured 1 month after MWA and 4 cycles after chemotherapy (3 months) to evaluate term effects; and 1- and 2-year survival rates. Serum VEGF concentrations declined sharply 1 day after MWA, and were significantly different from the levels before treatment. Subsequently, VEGF rebounded 7 days after ablation, higher than that before treatment. At 1 and 3 months, serum VEGF levels in both treatment groups were remarkably lower than that before treatment; efficiency, or for the 1-year survival rate. However, the 2-year survival rates were significantly different between the two groups. We demonstrated that after MWA, the serum VEGF concentration undergoes a process of increasing, which might promote metastasis and recurrence of NSCLC. MWA combined with whole-body chemotherapy appears to be an effective method to increase the disease control rate, reduce the probability of metastasis and recurrence, and thus improve long-term survival.

Impact of dendritic cells combining with cytokine-induced killer cells synergized chemotherapy in patients of advanced non-small cell lung cancer.

e19018 Background: Advanced non-small cell lung cancer (NSCLC) remains an incurable disease by following conventional chemotherapy and is the major cause of cancer–related mortality worldwide. Dendritic cells (DC) play a central role in the induction of an effective antitumor immune response. Cytokine-induced killer (CIK) cells, the subset of T lymphocytes, have a profound capacity to cytolytically eliminate cancer cells. This study was designed to evaluate how the times of receiving DC/CIKs vaccination following regular chemotherapy impact the overall survival time in patients of advanced lung cancer. Methods: 43 patients suffering from IIIB-IV NSCLC were enrolled in the study between August 2004 and December 2008, and all received four courses of vinolbine-platinum (NP) chemotherapy followed by vaccinated with carcinoembryonic antigen (CEA) peptide-pulsed autologus dendritic cells and CIK cells. Vaccination was repeated at 30-day intervals until the patient refused to accept. The adverse effect and overall survival (OS) were evaluated. Results: Median survival time (MST) of all patients was 19.50 months. The 1-, 2- and 3-year overall survival rate was 66.50%, 41.04%, 28.14% respectively. The 1-, 2- and 3-year overall survival rate of patients who received no less than two times of vaccination therapy was 83.92%, 74.59%, 49.73% and who received only one time was 59.44%, 23.71%, 17.78% respectively. A statistically significant difference between the two groups was identified (p=0.0052). The adverse effect as a result of chemoimmunotherapy was tolerable. Conclusions: Advanced NSCLC patients can benefit from the combination of DC-CIK vaccination followed conventional chemotherapy,and the more vaccination therapy received the longer overall survival time observed.

First-line cisplatin-fractionated doublet for unfit patients with advanced/metastatic non-small cell lung cancer.

e18072 Background: standard treatment for unfit patients (pts) with stage IIIB-IV non-small cell lung cancer (NSCLC) is single-agent chemotherapy. Such pts are usually not suitable for cisplatin (CDDP)-based chemotherapy due to poor performance status (PS) and/or significant comorbidity that could enhance toxicity of high-dose CDDP. They also are not able to tolerate hydric load that is recommended for CDDP at high doses. We investigated a schedule of fractionated CDDP as first-line treatment in unfit pts with stage IIIB/IV NSCLC. Methods: 42 consecutive unfit pts with advanced/metastatic NSCLC were treated. They all had ECOG PS 2 and/or significant comorbidity and were not eligible for a standard CDDP-based doublet. Median age was 65,6 years (range 46-77), stage IIIB/IV=15/27 pts. Histology: squamous 62,4%, adenocarcinoma 37,5%, other/NOS 0,1%. All pts received q3w CDDP 35 mg/mq d1-8 plus Gemcitabine 1000 mg/mq d1-8 or Pemetrexed 500 mg/mq d1 according to histology, for a maximum of 6 cycles. Maintenance Pemetrexed was allowed in pts with non-squamous histology. Progression-free survival (PFS), clinical benefit rate (CBR) and toxicity were evaluated. Results: 33 pts are evaluable for efficacy and 35 for toxicity. Mean number of cycles per patient was 5,03 (total 211). Maintenance with q3w Pemetrexed was performed in 10 pts (23,8%)(mean 4,3 cycles per patient). Five pts in response after CDDP received thoracic RT. A partial response was observed in 42,5% of pts and a stable disease in 35,4% of pts, for an overall CBR of 77,9%. Median PFS was 10,1 months (Kaplan-Meier); 31,9% of pts were progression-free at 1 year. Pts with adenocarcinoma had significantly better PFS than those with squamous histology (11 vs 8 months, p=0.03). G3-G4 haematological toxicity: neutropenia 48,4% (3% febrile), thrombocytopenia 27,2% and anaemia 9,0%. A 25% dose reduction was required in 39,3% of patients. One patient died for cardiac failure during treatment. Conclusions: fractionated CDDP seems to be effective in our patients population with advanced NSCLC. Adequate supportive care help to manage severe hematological toxicity. A randomized phase II trial of fractionated CDDP-doublet versus monotherapy has been planned.

Triplets versus doublets, with or without cisplatin, in the first-line treatment of stage IIIB–IV non-small cell lung cancer (NSCLC) patients: a multicenter randomised factorial trial (FAST)

Background:The FAST is a 2 × 2 factorial trial addressing two questions: (1) the role of replacing cisplatin (P) with a non-platinum agent, vinorelbine (N), and (2) the role of adding a third agent, ifosfamide (I), in a doublet based on gemcitabine (G).Methods:A total of 433 stage IIIB–IV non-small cell lung cancer (NSCLC) patients were randomised to one of four arms: gemcitabine–cisplatin (GP), gemcitabine–vinorelbine, gemcitabine–ifosfamide-cisplatin or gemcitabine–ifosfamide–vinorelbine. Two comparisons were performed: N- vs P-containing regimens and I-triplets vs non-I doublets.Results:For N- vs P-containing regimens, adjusted overall survival was 9.7 vs 11.3 months (P=0.044), progression-free survival was 4.9 vs 6.4 months (P=0.020) and response rate was 24% vs 31% (P=0.124), respectively. No statistically significant difference was observed between doublets and triplets. Grade 3–4 haematological toxicity was significantly more frequent in P-containing therapy; grade 3–4 leucopenia was significantly more common in triplets. Concerning non-haematological toxicity, grade 3–4 nausea-vomiting was significantly increased in P-containing regimens.Conclusions:This trial provides evidence of a slight survival superiority of GP-containing regimens over platinum-free N-containing chemotherapy. This trial also confirms that the addition of a third chemotherapy agent (I) to a standard G-based doublet does not improve treatment outcome.

Analysis of Prognostic Factors in Stage IIIB-IV Non-Small Cell Lung Cancer Cases who Received Chemotheraphy

Analysis of Prognostic Factors in Stage IIIB-IV Non-Small Cell Lung Cancer Cases who Received Chemotheraphy

A Phase II Study of Erlotinib as Initial Treatment for Patients with Stage IIIB-IV Non-small Cell Lung Cancer

Erlotinib improves survival in patients with advanced non-small cell lung cancer who have been previously treated with systemic chemotherapy. The current trial was designed to evaluate erlotinib as a primary therapy before chemotherapy in patients with minimally restricted eligibility criteria. Eligibility criteria included stage IIIB/IV or recurrent non-small cell lung cancer, no prior chemotherapy for systemic disease, performance status = 0 to 1, no history of brain metastases, and weight loss less than 10%. Patients received erlotinib 150 mg/d until objective or symptomatic progression when they were offered conventional chemotherapy. The primary end point was progression-free survival. Forty patients were accrued. The median age was 65 years, 35 had performance status = 1, 8 were never-smoker, and 23 were former smokers. Histologies were adenocarcinoma in 22 and squamous cell in six. The major toxicity was rash (grade 1, 12; grade 2, 16; grade 3, 3). Partial responses were observed in six (15%), stable in 11 (28%), and progressive disease in 23 (58%). The median time on erlotinib was 8 weeks. The median survival was 50 weeks with 1, 2, and 3 years survivals of 44%, 18%, and 16%. Retrospective epidermal growth factor receptor mutational analysis was performed in 18 subjects and four mutations (22%) were identified. Only 25 patients have received subsequent chemotherapy (too early, 4; refused, 9; and unable because of performance status, 2), and, of these, 9 (36%) achieved unconfirmed responses. Despite a modest response rate, lack of enrichment for never-smokers and absence of conventional chemotherapy in many patients, the median and long-term survivals were comparable with those expected after conventional sequencing of chemotherapy. Erlotinib as initial therapy was well tolerated and warrants randomized evaluation as first-line treatment for advanced lung cancer.