Chemotherapy In NSCLC Research Articles

81 Audit of 1 year survival for patients receiving chemotherapy for NSCLC – all comers

81 Audit of 1 year survival for patients receiving chemotherapy for NSCLC – all comers

Anti-angiogenesis in Personalized Therapy of Lung Cancer.

Upregulation of angiogenesis is a frequent occurrence in lung cancer and is reported to represent a negative prognostic factor. This provides a rationale for the development and evaluation of anti-angiogenic agents. To date bevacizumab, a monoclonal antibody directed against serum VEGF, is the only anti-angiogenic agent that has demonstrated improved overall survival for patients with lung cancer. Meta-analysis of trials of bevacizumab in combination with platinum-based chemotherapy for NSCLC, show a 10% reduction in the risk of death (HR 0.90, 95% CI 0.81-0.99). However, therapy with bevacizumab is limited to NSCLC patients with non-squamous histology, good performance status, no brain metastases and the absence of bleeding or thrombotic disorders. More recently, similar survival was observed in a non bevacizumab containing regimen of carboplatin, pemetrexed and maintenance pemetrexed. Multiple oral anti-angiogenic compounds have been evaluated in NSCLC, both in first-line therapy, or upon disease progression. The majority of agents have shown some evidence of activity, but none have clearly demonstrated improvements in overall survival. Increased toxicities have been observed, including an increased risk of death for some agents, limiting their development. Promising data exist for sunitinib in patients with heavily pre-treated NSCLC, and nintedanib in combination with docetaxel, as second-line therapy for NSCLC. However, these findings require validation. Currently, there is no established role for anti-angiogenic therapy in SCLC, although there is some promise for sunitinib as maintenance therapy following platinum and etoposide chemotherapy. The challenge for anti-angiogenic therapy is to understand whether treatment effects in a subpopulation, are lost among a larger unselected population of patients. There is a need for additional translational research to identify predictive biomarkers for anti-angiogenic therapy.

NEOADJUVANT CHEMOTHERAPY IN NON-SMALL CELL LUNG CANCER (NSCLC): CURRENT STATUS

The role of neoadjuvant chemotherapy in NSCLC still remains unclear. It may be useful in the treatment of resectable NSCLC like in other solid tumors. Only prospective studies will answer this question. Determination of optimal candidates for comparative studies of preoperative and postoperative chemotherapy in practice is a challenge. The best approach for patients with I and II stages of NSCLC is to provide combined treatment including surgery and adjuvant chemotherapy, and for patients with borderline resectable tumors with stages IIB, IIIA, but with minimal or without involvement of mediastinal lymph nodes is to provide neoadjuvant chemotherapy. For today, traditional ways of improving chemotherapy of NSCLC are exhausted, however, in connection with the development of recombinant cytokines (available for Phase I clinical trials), it opened real possibilities for clinical research on the development and evaluation of methods of neoadjuvant chemoimmunotherapy of NSCLC.

TIME Trial: Efficacy of TG4010 Immunotherapy With First-Line Chemotherapy in NSCLC

TIME Trial: Efficacy of TG4010 Immunotherapy With First-Line Chemotherapy in NSCLC

128P - Comparison of Efficacy of Pemetrexed Plus Platinum and Non-Pemetrexed Plus Platinum as 1St Line Chemotherapy in EGFR Wild Type Non-Squamous Nsclc

Aim: Despite of huge development of molecular research and target agents, patients with EGFR wild type NSCLC who accounted for more than a half of NSCLC patients still have to receive platinum doublet chemotherapy in 1st line treatment. Because only a little research has been conducted with EGFR wild type NSCLC patients, we investigated efficacies of various platinum doublet regimens in these patients.

Maintenance chemotherapy in advanced NSCLC: a population-based assessment of eligibility.

Maintenance chemotherapy has been incorporated into treatment paradigms for advanced NSCLC. Eligibility criteria include stable disease/partial response and PS 0-1 after a first line platinum doublet. In practice, maintenance can be difficult to deliver due to patient factors and preferences. We propose to examine the proportion of patients eligible for maintenance and factors associated with the delivery of subsequent lines of chemotherapy. The BC Cancer Agency provides care to a population of 4.5 million. A retrospective review was conducted of all referred Stage IIIB/IV patients in 2009 who received first line systemic therapy. Baseline characteristics, PS and response after first line and subsequent systemic therapy details were recorded. Patients were deemed potentially maintenance eligible or not based on clinical trial criteria; however maintenance therapy was not delivered to these patients as it was not yet available. 330 patients were identified; 98 were potentially maintenance eligible. The reason for maintenance ineligibility in n = 232; no upfront doublet (n = 41), PS ≥ 2 (n = 38), progressive disease (PD) (n = 53), PS ≥ 2 and PD (n = 62), PS ≥ 2 and unknown response (n = 35), PD and unknown PS (n = 3). Further chemotherapy (2nd line or beyond) was administered in maintenance eligible 68% vs ineligible 56%. Reasons for no further chemotherapy were predominantly decline in PS and brain metastasis. Median OS: 7 m for 1st line only versus 16.8m for ≥ 2 nd line (p < 0.001). In our population based study, 30% of advanced NSCLC patients were eligible to receive maintenance chemotherapy based on the clinical trial criteria. Despite a good initial PS and disease control only 68% of maintenance eligible patients received subsequent therapy. A clear survival benefit was seen with ≥ 2 nd line treatment. Maintenance therapy or initiation of early second line therapy should be considered for advanced NSCLC patients to improve survival outcomes.

Efficacy and Safety Results From a Phase 2, Placebo-Controlled Study of Onartuzumab Plus First-Line Platinum-Doublet Chemotherapy in Advanced Squamous-Cell Non-Small Cell Lung Cancer (sq NSCLC): Metastatic Non-Small Cell Lung Cancer

The monovalent monoclonal antibody onartuzumab (O) binds with the extracellular domain of the MET receptor in place of hepatocyte growth factor (HGF), thus blocking MET signaling. A phase 2 study combining O with erlotinib in pretreated NSCLC suggested that O could improve progression-free survival (PFS) and overall survival (OS) vs placebo (Pb) in MET IHC+ patients (pts). The GO27820 study was designed to investigate whether adding O would improve the efficacy of first-line platinum-doublet chemotherapy for sq NSCLC, a subtype with few treatment options.

WS6-4 - Chemotherapy for Non-Aids Defining Cancers, Focused on Lung Cancer

HIV infection has become a chronic disease with the advent of combination antiretroviral therapy. As the result of long survival among the patients living with HIV, the death by non-HIV defining cancers is increasing because of their aging. Non-AIDs defining hematological malignancies have been relatively reported, however, solid tumors, mainly lung cancer, are recently increasing as well. In Japan, the cancer patients living with HIV are also increasing although treatment is still limited in specific hospitals, whereas HIV infection is becoming a “not-rare-complication” in the United States. Lung cancer patients living with HIV is associated with a high frequency of smoking, whereas hepatocellular carcinoma and anal cancer/cervical cancer are associated with HBV and HPV, respectively.The prognosis of the lung cancer patients living with HIV is extremely poor compared to those of the non-HIV population. It was controversial whether chemotherapy for lung cancer patients living with HIV will be of clinical benefit because of increased toxicities related to interactions with antiretroviral therapy, weakening immunity, decreased bone marrow reserve or other organ functions. However, recent treatment progress for the cancer patients living with HIV has led us to believe in improving the prognosis, especially the progress in this decade of chemotherapy for advanced NSCLC among non-HIV population with the advent of molecular targeted drugs or diverse treat strategies in combination with chemotherapy agents.Still, it remains unclear whether adopting the cancer guidelines of standard of care for non-HIV cancer patients is beneficial or not, because the cancer patients living with HIV has been excluded from most clinical trials. Either way, cancer treatment has become specified and more diverse, so clinical management should be done by medical oncologists. Additionally, collaborative team treatment is also essential for cancer patients living with HIV.

P1-17-4 - Efficacy of Carboplatin + Weekly Nab-Paclitaxel for Elderly Advanced/Recurrent Non-Small Cell Lung Cancer(E-Nsclc)

Background: French trial showed survival advantage of carboplatin (Cb) + weekly PAC doublet over monotherapy for E-NSCLC patients. Elderly subset of CA310 trial suggested improved overall survival by Cb + weekly nab-paclitaxel (wnPAC) compared with standard Cb + PAC. These trials suggested that Cb + wnPAC could be a reasonable treatment option for E-NSCLC. To examine the efficacy of Cb + wnPAC for E-NSCLC, we conducted a retrospective analysis of the patients who underwent this chemotherapy.Methods: Ten patients aged 75 or older received Cb + wnPAC as the first-line chemotherapy for advanced or recurrent NSCLC. Data of these patients were extracted from electronic medical records. The dose and schedule of the treatment were based on CA310 trial. The treatment was repeated up to 4 courses.Result: Patient characteristics were as follows: Median age 76 (range: 75-78); all male; histology (Sq/Ad/NOS) 6/2/2; PS (0/1/2) 5/2/3; stage (IIIB/IV/recurrent) 2/3/5. Delivered number of courses was 4 in median. Actual/planned dose intensity were 87.5% and 67.3% for Cb and nab-PAC, respectively. Responses by RECIST were PR in 5, SD in 2 and PD in 3. Treatment delay and skip was experienced in 4 and 6 cases, respectively. Dose reduction was needed in 5 cases. Grade 3/4 neutropenia, thrombocytopenia and anemia were experienced in 7, 3 and one patients, respectively. Non-hematological toxicity of G3 was observed in 2 patients (anorexia and fatigue in one, and enterocolitis in the other). No febrile neutropenia or grade 3 neuropathy was observed.Conclusion: Cb + wnPAC can be a good treatment option for E-NSCLC.

Multi-Arm, Nonrandomized, Open-Label Phase Ib Study to Evaluate Fp1039/Gsk3052230 with Chemotherapy in Nsclc and Mpm with Deregulated Fgf Pathway Signaling

ABSTRACT Background: FP1039/GSK3052230 (GSK230) is a soluble fusion protein that acts as a ligand trap by sequestering fibroblast growth factors (FGFs) involved in tumor growth. FGF ligand-dependent signaling plays an important role in cancer development and growth through autocrine production of FGFs from cancer cells, or paracrine production of FGFs from local stroma, or by tumor overexpression of FGF receptors (FGFRs) or amplification of FGFR genes. FGFR1 amplification has been identified in ∼15-20% of squamous non-small cell lung cancers (NSCLC) and is associated with shorter disease-free and overall survival. Efficacy was observed with GSK230 + chemotherapy in FGFR1 amplified in NSCLC xenograft models and in xenograft models of malignant pleural mesothelioma (MPM) where FGF2 mRNA levels were overexpressed. In a phase I study, no maximum tolerated dose (MTD) was identified and 20 mg/kg weekly was the maximum feasible dose (MFD) achieving the desired target concentration. Toxicities associated with small-molecule FGFR inhibition, namely hyperphosphatemia and retinal, nail, and skin changes, were not observed. Trial design: This is a multi-arm, nonrandomized, open-label phase IB study designed to evaluate the safety and preliminary efficacy of GSK230 in combination with paclitaxel + carboplatin in previously untreated FGFR1 amplified metastatic squamous NSCLC (Arm A), in combination with docetaxel in FGFR1 amplified metastatic squamous NSCLC that has progressed after 1 line of chemotherapy (Arm B), or in combination with pemetrexed + cisplatin in patients with untreated and unresectable MPM (Arm C). Approximately 70 patients will be enrolled. Each arm involves a dose escalation phase utilizing the 3 + 3 design, followed by a cohort expansion phase of at least 12 patients treated at either MTD or MFD. GSK230 will be administered as a 30-minute intravenous infusion once a week in a 21-day cycle. The starting dose is 5 mg/kg and will be dose escalated until MTD or MFD in combination with chemotherapy is reached. Endpoints include the combination dose of GSK230 with chemotherapy, safety, response rates and their duration, and translational objectives (NCT01868022). Disclosure: P. Garrido: I don't have any specific conflict interest related to this trial except from being part the clinical trial; E. Felip: Advisory boards for BI, Novartis, Roche, BMS and Lilly; F. Barlesi: Honorarium from GSK; P.K. Paik: Research funding provided by GlaxoSmithKline, BristolMyersSquibb; D. Morgensztern: Member of Advisory Board – Celgene Speaker – Boehringer Ingelheim; K. Reckamp: GSK provided research funding to institution. All other authors have declared no conflicts of interest.

A Prospective Study of Bevacizumab and Platinum-Based Chemotherapy in NSCLC: Comparison of the Prognostic Value of Early Imaging Response Assessment Criteria and Intratumoral Heterogeneity Analysis

A Prospective Study of Bevacizumab and Platinum-Based Chemotherapy in NSCLC: Comparison of the Prognostic Value of Early Imaging Response Assessment Criteria and Intratumoral Heterogeneity Analysis

Cisplatin Plus Pemetrexed (Cp) Versus Cisplatin Plus Gemcitabine (Cg) According to Thymidylate Synthase Expression in Non-Squamous Nsclc: a Biomarker-Stratified Randomized Phase Ii Trial

ABSTRACT Aim: JMDB trial showed CP was significantly superior to CG in non-squamous NSCLC, while CP was inferior in squamous NSCLC. Thymidylate synthase (TS) is one of target proteins of pemetrexed and the efficacy of pemetrexed-based chemotherapy could depend on TS expression. The primary endpoint is to determine the predictive value of TS in non-squamous NSCLC in terms of objective response rate (RR) by testing on the interaction between treatment arm and TS positivity. Methods: Main inclusion criteria are non-squamous NSCLC excepting for large cell neuroendocrine carcinoma, one or more measurable lesions, and no prior chemotherapy for advanced NSCLC. Written consents were obtained from eligible patients, and TS expression was collected by IHC. The patients with more than 10% of tumors expressing TS were grouped as a TS(+) and those with 10% or less were grouped as a TS(-). After being stratified as TS(+) or TS(-), patients were randomized to either CP or CG arms by 1: 1 fashion. CP or CG was administered until disease progression or unacceptable toxicity with maximum 6 cycles. Response evaluation was done every 2 cycles during treatment and every 2 months after completion of study chemotherapy. One-sided alpha of 0.1 was used for testing on the interaction term. Otherwise, all p-values are two-sided. Results: For 315 evaluable patients, the RR of CP and CG were 47.0% and 21.1% in TS (-) group, whereas 40.3% and 39.2% in TS (+) group (interaction P = 0.008). The RR of CP and CG arms evaluated by independent reviewers were 38.6% and 21.1% in TS(-) group, and 40.3% and 48.1% in TS(+) group (interaction P = 0.007). The median PFS of CP and CG were 6.4 and 5.5 months in TS (-) group (P = 0.013), whereas 5.9 and 5.3 months in TS (+) group (P = 0.64) (interaction P = 0.07). The median OS of CP and CG were not different in TS (-) group (not reached vs. 28.3 months, P = 0.86) and in TS (+) group (19.0 vs. 14.4 months, P = 0.36) (interaction P = 0.31). TS-negativity was an independent prognostic factor for OS (HR = 0.64, 95% CI 0.45-0.90). Conclusions: In terms of RR and PFS, clinical benefits of CP chemotherapy compared to CG were more prominent in TS (-) group than in TS (+) group, suggesting that TS can be used as a predictive biomarker. Furthermore, given that low TS expression was associated with prolonged OS irrespective of chemotherapeutic regimens, TS expression can also serve as a prognostic biomarker. Disclosure: All authors have declared no conflicts of interest.

Brain Metastases Safely Treated with WBRT after Bevacizumab and Chemotherapy in NSCLC

Patients who had brain metastases following bevacizumab and chemotherapy (CT) for non-squamous, non—small cell lung cancer (non-Sq NSCLC) were safely treated with whole-brain radiotherapy, with a good response and symptom improvement.

Multiarm, nonrandomized, open-label phase IB study to evaluate FP1039/GSK3052230 with chemotherapy in NSCLC and MPM with deregulated FGF pathway signaling.

TPS8120 Background: FP1039/GSK3052230 (GSK230) is a soluble fusion protein that acts as a ligand trap by sequestering fibroblast growth factors (FGFs) involved in tumor growth. FGF ligand-dependent...

K-ras mutation for prediction of response to chemotherapy plus autophagy inhibition in NSCLC.

e19069 Background: Autophagy (ATG) preserves growth potential during cellular stresses and may promote chemotherapy resistance. K-ras deficient mouse models depend on ATG for tumor growth. Hydroxychloroquine (HCQ) inhibits ATG in in vitro and in vivo models, and may thus enhance chemotherapy effect. Methods: We conducted phase II studies of q 21 day chemotherapy up to 6 cycles with paclitaxel 200 mg/M2 with carboplatin AUC=6, and bevacizumab (Bev) (per Bev criteria) 15mg/Kg, together with daily p.o. HCQ at 200 mg bid (25 patients), and 600 mg bid (2 patients, ongoing); then followed by daily p.o. HCQ and Bev (per Bev criteria) as maintenance for up to one year. Results: We entered 27 patients (16M/11F) median PS=1, Median age = 70. Overall we saw 0 CR, 14 PR, 5 SD, 6 PD, and 2 TE. Median TTP = 7+ months, OS = 10+ months. Neutropenia, grade 3 and 4 was the predominant toxicity. Among 9 patients with prospectively assayed k-ras status: k-ras wild-type showed 1PR and 2PD; k-ras mutant showed 4 PR, 1 SD, 1 PD, and 1 TE. We are currently obtaining tissue, where available, for retrospective k-ras assay for those cases not assayed. Conclusions: ATG inhibition may augment chemotherapy response, preliminary data suggest a predictive role of k-ras in response to this regimen, and the retrospective kras assay may thus be helpful. Study continues at higher HCQ levels to reach free drug levels of HCQ. Clinical trial information: NCT01649947.

P0158 Relation between polymorphisms and chemotherapy in lung cancer

Background Lung cancer is the leading cause of cancer-related death globally. Chemotherapy and targeted drugs increase progression-free survival, overall survival, and quality of life. Recently, we are moving towards personalised medicine based on genotypic study of enzymes involved in the metabolism, transport, and elimination of drugs routinely used in lung cancer. Methods After obtaining written informed consent, we analysed venous blood draws from 40 patients with NSCLC of all stages, before the start of chemotherapy. We studied polymorphisms, with real-time PCR, in genes involved in detoxification (GSTP1), DNA repair (XRCC1, ERCC1) in trans-membrane transport (ABCB1), and metabolism of anticancer agents (CYP2C9, CYP3A4, CYP3A5, CYP2D6, CYP1A2, UGT1A1, TSER). Findings We are prospectively analysing the correlation between polymorphisms and toxicity of chemotherapy regimens and progression-free survival, overall survival, and quality of life. We expect a greater toxicity in patients with polymorphisms that result in reduced activity of enzymes involved in drugs metabolism, a reduction in transport, and in DNA repair activity. Interpretation Considering that there is no standard first-line chemotherapy for NSCLC, since platinum-based regimens are equally effective, the toxicity of each regimens affects choice of treatment. Therefore, the objective of this study is to identify factors that can direct choice of chemotherapy regimen based on the patient’s genotype.

EP-1170: Role of postoperative radiotherapy after adjuvant chemotherapy in pN2 NSCLC: A propensity score matching analysis

EP-1170: Role of postoperative radiotherapy after adjuvant chemotherapy in pN2 NSCLC: A propensity score matching analysis

OC-0062: An invidual data metaanalysis of phase II trials of adjuvant or induction chemotherapy for NSCLC treated with chemoRT

OC-0062: An invidual data metaanalysis of phase II trials of adjuvant or induction chemotherapy for NSCLC treated with chemoRT

O3–097 - Phase II Study of Bevacizumab Plus CBDCA/PAC as First Line Chemotherapy for Non-SQ NSCLC with Malignant Pleural Effusion

O3–097 - Phase II Study of Bevacizumab Plus CBDCA/PAC as First Line Chemotherapy for Non-SQ NSCLC with Malignant Pleural Effusion

PO84 VISUALIZING TREATMENT AND OUTCOMES IN METASTATIC BREAST CANCER

Background: Treatment of MBC is becoming more complex as more drugs are approved for this indication. A high proportion of these drugs are intravenous, and sequential use can have a detrimental effect on venous access, causing distress to the patient as well as preventing treatment. In the UK vinorelbine is licensed for the treatment of MBC and NSCLC as a single agent or in combination. Vinorelbine is a vesicant and when given intravenously can cause venous irritation, which in some cases can lead to thrombophlebitis. Administration site reactions are very common, occurring in more than 10% of patients (grade 3/4: 3.7%). We compared the incidence of venous toxicity with IV vinorelbine in patients with MBC and those with NSCLC, who generally receive vinorelbine as their first chemotherapy. Method: Case notes of all patients receiving IV vinorelbine during a 3 year period (2008 to 2011) at UHNS were reviewed retrospectively for incidence of thrombophlebitis. Results: We identified 39 patients; 11 received vinorelbine IV as a single agent for MBC whilst 28 received it with platinum as adjuvant chemotherapy for NSCLC. Median age was 55 and 67 years for MBC and NSCLC patients respectively. Patients with MBC had previously received at least 2 lines of chemotherapy (maximum of 5 previous lines), including combination regimens and nearly all had been administered IV, whereas all patients with NSCLC were chemo-naive. Almost half of the patients with MBC had prior history of venous access problems. Four required central line insertions for vinorelbine treatment. A total of 57 cycles (mean 5.1) were delivered for MBC and 93 cycles (mean 3.3) were delivered for NSCLC. Moderate to severe thrombophlebitis was recorded in 8 of the 11 patients with MBC (80%), compared to only 1 (3%) with NSCLC. A further two patients with MBC experienced mild thrombophlebitis and problems also occurred in a further four patients despite them having a central line inserted. Other side effects occurred at similar rates in both groups, apart from haematological toxicity which was slightly more pronounced in patients with NSCLC and probably related to combination treatment. Conclusions: Venous complications were frequent with intravenous administration of vinorelbine. A significantly higher incidence of thrombophlebitis was seen in patients with MBC. This was probably due vein damage from multiple lines of previous chemotherapy. We recommend consideration of oral administration of vinorelbine to reduce the need for central line insertion and to improve the patient experience and compliance.