Stage IIIB-IV Non-small Cell Lung 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.

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.

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.

Gender Differences in Treatment Outcomes among Patients with Non-Small Cell Lung Cancer Given a Combination of Carboplatin and Paclitaxel

Objectives: It was the aim of this study to investigate gender differences in the outcomes of carboplatin and paclitaxel chemotherapy in patients with unresectable stage IIIB-IV non-small cell lung cancer (NSCLC). Methods: Gender, age, performance status, histology, hematological toxicity, tumor responses and survival parameters obtained retrospectively by medical chart review were analyzed. Results: A total of 227 patients (147 males and 80 females) were included. The median lowest leukocyte count was 2,900 (range 1,200–12,400)/µl in males and 2,200 (range 600–6,500)/µl in females (p < 0.001). Grade 3–4 leukopenia was noted in 15% of male and in 39% of female patients (p < 0.001). In both genders, the response rate in evaluable patients was 39%. The median progression-free survival was 4.4 months for men and 5.3 months for women (p = 0.0081). After progression of the disease, gefitinib was administered in 64 (44%) male and 45 (56%) female patients, with a median treatment of 35 and 144 days, respectively. The median survival time was 11.9 months for men and 22.2 months for women (p < 0.001). Conclusion: Female gender was associated with a favorable prognosis in patients with NSCLC who received carboplatin and paclitaxel chemotherapy, although the response rates did not differ between the genders. Of note, hematological toxicity was more severe in female patients.

Effects of nutritional intervention in non-small cell lung cancer patients with different levels of systemic inflammation

20631 Background: In cancer cachexia systemic inflammation and nutrition-related factors may independently contribute to mortality. Recently treatment with a cysteine-rich protein (CyP) was found to increase body weight and survival in non-small cell lung cancer patients (Tozer et al. Antioxidants & Redox Signaling 2008, 10:395–402). It is not known whether patients with systemic inflammation may also benefit from this nutritional intervention. Methods: The data set from this study has now been analyzed to determine whether patients with high C-reactive protein (CRP) concentrations and/or high white blood cell (WBC) counts, i.e., a subgroup with “strong systemic inflammation” (SSI), may show less benefit than the subgroup with ‘little or no systemic inflammation‘ (LNSI). Sixty-six patients with Stage IIIB-IV non-small cell lung cancer were randomly assigned to CyP or casein, a widely used protein supplement low in cysteine. Included were patients with a previous involuntary weight loss of ≥3%, and Karnofsky status ≥70. Results: All LNSI patients with CyP survived for at least one year and showed a mean increase in Karnofsky status. Survival and Karnofsky status were decreased in both, the SSI subgroup with CyP and the LNSI subgroup with casein. The SSI and LNSI subgroups of the casein group were not significantly different. Conclusions: Poor survival is associated with either condition, systemic inflammation or inadequate nutrition. As CyP and casein are isocaloric and isonitrogenous, their differential effects may be related to the content of cysteine, a precursor of glutathione. Cysteine deficiency and systemic inflammation may be mechanistically related and not necessarily independent factors. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Immunotec Inc. Immunotec Inc. Immunotec Inc.

Baseline elevated leukocyte count in peripheral blood is associated with poor survival in patients with advanced non-small cell lung cancer: a prognostic model

We aimed to investigate the prognostic significance of several baseline variables in stage IIIB-IV non-small cell lung cancer to create a model based on independent prognostic factors. A total of 320 patients were treated with last generation chemotherapy regimens. The majority of patients received treatment with cisplatin + gemcitabine or gemcitabine alone if older than 70 years or with an ECOG performance status (PS) = 2. Performance status of 2, squamous histology, number of metastatic sites >2, presence of bone, brain, liver and contralateral lung metastases and elevated leukocyte count in peripheral blood were all statistically significant prognostic factors in univariate analyses whereas the other tested variables (sex, stage, age, presence of adrenal gland and skin metastases) were not. Subsequently, a multivariate Cox's regression analysis identified PS 2 (P < 0.001, hazard ratio 2.57), elevated leukocyte count (P < 0.001, hazard ratio 1.79), squamous histology (P = 0.005, hazard ratio 1.45) and presence of brain metastases (P = 0.035, hazard ratio 1.5) as independent prognostic factors for poor survival. Patients were assigned to one of three risk groups according to the cumulative risk defined as the sum of simplified risk scores of the four independent prognostic factors. Low-, intermediate- and high-risk patients achieved a median survival of 10.2 months (95% confidence interval (CI) 8.9-11.6), 5.1 months (95% CI 4.0-6.2) and 2.8 months (95% CI 0.5-5.2), respectively. The high-risk group encompassed PS 2 patients with two or three adjunctive unfavourable independent prognostic factors. Performance status, white blood cells count, histology and brain metastases resulted in our series prognostic factors of survival in NSCLC patients treated with chemotherapy at a multivariate analysis. Leukocyte count resulted the stronger factor after performance status. If prospectly validated, the proposed prognostic model could be useful to stratify performance status 2 patients in specific future trials.

Comparison of vinorelbine-Cisplatin with gemcitabine-Cisplatin in patients with advanced non-small cell lung cancer.

The objective of this trial was to compare cisplatin-plus-vinorelbine regimen with cisplatin-plus-gemcitabine regimen in patients with stage IIIB-IV non-small cell lung cancer (NSCLC). Chemonaive patients with stage IIIB-IV NSCLC received either vinoelbine 30 mg/m(2) (days 1 and 8) plus cisplatin 80 mg/m(2) (day 1) every 21 days (VC arm) or gemcitabine 1250 mg/m(2) (days 1 and 8) plus cisplatin 80 mg/m(2) (day 1) every 21 days (GC arm). One hundred thirtyfour patients (67 VC and 67 GC) were included to the study. Overall response rates for the VC arm (31.2%) were not significantly different from that of the GC arm (34.3%). There were no differences in overall survival and one-year survival rates. Median survival and one-year survival rates for the VC and GC groups were 10.6 and 11.5 months, 45% and 46.8%, respectively. Grade 3-4 thrombocytopenia was significantly higher on the GC arm (VC 1.4% v GC 8.9%, p < 0.05), as was febrile neutropenia on the VC arm (VC 8.9% v GC 1.4%, p < 0.05). VC and GC demonstrated similar efficacy but there were differences in toxicity profiles.