Carboplatin Paclitaxel Research Articles

320P Adjuvant chemotherapy comprising a paclitaxel and carboplatin regimen or paclitaxel and ifosfamide regimen for uterine carcinosarcoma, a single institutional retrospective study

Background Uterine carcinosarcoma (UCS) is a rare form ofcancer with poor prognosis.Itisunclearwhetheradjuvantchemotherapyimprovestheprognosisinthese patients. The aim of this retrospective study was to assess the efficacy of adjuvant chemotherapyafter primarysurgeryfor UCS. Methods Dataforpatients whounderwentcomletesurgicalresection ofUCS between 2002 and 2015 were retrospectively analyzed. The patients were classified into three groups: those who did not receive adjuvant chemotherapy (the surgery only group), those who received paclitaxel and carboplatin (TC; carboplatin AUC6 + paclitaxel 175mg/m2 q3w, 6 cycles; TC group), and those who received paclitaxel and ifosfamide (TI; ifosfamide 1.6g/m2 + paclitaxel 175mg/m2 q3w, 8 cycles; TI group).We compared the recurrence-free survival (RFS) and overall survival (OS) among the three groups. Results: A total of 41 patients were identified, with 20 patients in the surgery only group, 7 patients in the TC group, and 14 patients in the IT group. The patient and tumor characteristics in the surgery only group, TC group, and TI group were as follows,respectively:(meanage)63.5;56.0;62.0,(clinicalstageI/II/II/IV)10/0/8/2;1/1/ 3/2;11/1/6/2,(homologous/heterologouswithsarcomacomponent)11/9;5/2;11/3,and (endometrioid/serous/not determined in carcinoma component:) 11/2/7; 1/4/2; 6/7/1. No significant differences in these characteristics were observed between the three groups. Moreover, TC or TI group did not demonstrate significant defferrence in RFS (P = 0.558,0.410) and OS (P = 0.844,0.663) comparedwiththe surgery onlygroup. Conclusions: Accordingtothefindingsofthisstudy,adjuvantchemotherapydidnot improve the RFS and OS in patients with UCS after complete surgical resection. However, the retrospective nature of the study and a small sample size warrant further studies for a definitive conclusion. Legal entity responsible for the study Yohei Ohtake Funding Japan Agency for MedicalResearch and Development Disclosure All authors have declared no conflicts ofinterest.

Hsp90 Inhibitor Ganetespib Sensitizes Non-Small Cell Lung Cancer to Radiation but Has Variable Effects with Chemoradiation.

HSP90 inhibition is well known to sensitize cancer cells to radiation. However, it is currently unknown whether additional radiosensitization could occur in the more clinically relevant setting of chemoradiation (CRT). We used the potent HSP90 inhibitor ganetespib to determine whether it can enhance CRT effects in NSCLC. We first performed in vitro experiments in various NSCLC cell lines combining radiation with or without ganetespib. Some of these experiments included clonogenic survival assay, DNA damage repair, and cell-cycle analysis, and reverse-phase protein array. We then determined whether chemotherapy affected ganetespib radiosensitization by adding carboplatin-paclitaxel to some of the in vitro and in vivo xenograft experiments. Ganetespib significantly reduced radiation clonogenic survival in a number of lung cancer cell lines, and attenuated DNA damage repair with irradiation. Radiation caused G2-M arrest that was greatly accentuated by ganetespib. Ganetespib with radiation also dose-dependently upregulated p21 and downregulated pRb levels that were not apparent with either drug or radiation alone. However, when carboplatin-paclitaxel was added, ganetespib was only able to radiosensitize some cell lines but not others. This variable in vitro CRT effect was confirmed in vivo using xenograft models. Ganetespib was able to potently sensitize a number of NSCLC cell lines to radiation but has variable effects when added to platinum-based doublet CRT. For optimal clinical translation, our data emphasize the importance of preclinical testing of drugs in the context of clinically relevant therapy combinations. Clin Cancer Res; 22(23); 5876-86. ©2016 AACR.

190P - Measurement of molecular biomarkers to predict tumor response in estrogen receptor positive breast cancer after dose-dense (biweekly) paclitaxel/carboplatin neoadjuvant chemotherapy

Dose-dense (biweekly) paclitaxel/carboplatin(PC) as neoadjuvant Chemotherapy (NCT) for operable breast cancer is feasible and efficient. This study was to analysis the relationship between the molecular biomarkers and tumor response in estrogen receptor(ER) positive breast cancer. 84 ER-positive breast cancer patients treated with Dose-dense (biweekly) paclitaxel/carboplatin NCT were analyzed for expression of progesrone receptor (PgR), Tau, ki67, HER2, Bcl-2 by immunohistochemistry (IHC), these data were used to test whether these biomarkers can predict tumor response. The primary endpoint was a pathologically complete response (pCR). The second endpoint was the change in tumor size between pre and post NCT. Univariate analysis showed that HER2 positive (53.85% vs 8.62%, p < 0.01,Tau negative (40.91% vs 16.13%,p = 0.017, BCL-2 negative (48.15% vs 10.53%, p < 0.01) expression were associated with higher pCR rate. Multivariate analysis revealed that HER2 (OR: 8.116; 95%CI: 1.931-34.115; p = 0.04), BCL-2(OR: 0.176; 95%CI: 0.041-0.746; p = 0.018) were independent pCR predictive biomarkers. Tumor size was significant reduced in HER2 positive (p = 0.001, high-level ki67 (p = 0.007, Tau negative (p = 0.002, BCL-2 negative (p = 0.008) breast cancer. This study investigates the value of traditional biological markers, Bcl-2 and Tau in ER-positive patients treated with dose-dense (biweekly) paclitaxel/carboplatin NCT.

Adherence to Hematologic Hold Parameters in Carboplatin and Dose-Dense Paclitaxel Chemotherapy for Ovarian Malignancies: A Survey of NCCN Member Institutions.

To determine the adherence to hematologic chemotherapy hold parameters for the carboplatin and dose-dense paclitaxel chemotherapy regimen in patients with ovarian, fallopian tube, or primary peritoneal cancers. This is a quality assessment survey study. All 26 NCCN Member Institutions were contacted electronically. Hematologic chemotherapy hold parameter values (absolute neutrophil count [ANC] and platelet count) on days 1, 8, and 15 of each cycle were queried. These hold parameters were compared with published data supporting the use of dose-dense chemotherapy regimens in ovarian cancer. The overall survey response rate was 85% (22/26 sites). Of responders, 27% (6 sites) were fully adherent with all hematologic hold parameters and 64% (14 sites) used hold parameters that differed from the published protocol. Specifically, all of these sites use hold parameters higher than those recommended in the literature. Two centers did not have center-specific hold parameters. Carboplatin and dose-dense paclitaxel chemotherapy has been shown to increase progression-free survival and overall survival in patients with stage II-IV ovarian, fallopian tube, or primary peritoneal cancers. However, our study found that two-thirds of queried sites had hold parameters higher than those in the published protocol. Using more stringent hold parameters may lead to compromised clinical outcomes. Further research is necessary to determine the optimal strategy to increase individual site adherence to chemotherapy hematologic hold parameters as specified in published trials.

Prognostic and predictive blood-based biomarkers (BMs) in patients (pts) with advanced epithelial ovarian cancer (EOC) treated with carboplatin–paclitaxel (CP) ± bevacizumab (BEV): Results from GOG-0218.

5521Background: GOG-0218, a double-blind placebo (PLA) controlled phase III trial of 1873 pts with advanced EOC, compared CP with either PLA (CPP), BEV 15 mg/kg q3w → PLA (CPB15), or BEV 15 mg/kg q...

Analysis of safety and outcome of the combination of carboplatin (C) paclitaxel (P) and bevacizumab (B) in advanced/recurrent cervical cancer (ACC).

e17015Background: Combination of Cisplatin , Paclitaxel and Bevacizumab has demonstrated a better RR, PFS and OS than Chemotherapy alone in ACC (Tewary K et al. N Engl J Med; 2014, 370:734-743) How...

Phase II trial of carboplatin, paclitaxel and temozolomide in metastatic melanoma.

e21012Background: Temozolomide (TMZ) as single agent and combination of carboplatin paclitaxel are active as first and second line therapies for metastatic melanoma (MM). Although immune and target...

Improved outcomes with dose-dense paclitaxel-based neoadjuvant chemotherapy in advanced epithelial ovarian carcinoma

ObjectiveWe compared tolerability, toxicity, response, and interval debulking surgery (IDS) outcomes between patients who received weekly dose-dense paclitaxel (DDP) and every three-week platinum to standard every three-week taxane plus platinum neoadjuvant chemotherapy (NACT) for advanced epithelial ovarian cancer (EOC). MethodsWe conducted a retrospective study of patients receiving NACT at our center between June 1, 2012 and July 31, 2015. Patients with stage III/IV EOC who received at least one cycle of DDP (weekly paclitaxel plus every three-week carboplatin) or standard taxane (every three-week paclitaxel or docetaxel plus carboplatin) therapy were included. Abstracted data included demographics, tolerability, grade 3/4 toxicity, response, and IDS outcomes. Fisher's exact and student t-test were used for statistical significance. ResultsTwenty-one patients received DDP and 40 received standard taxane. Tolerability was comparable. More patients receiving DDP experienced grade 3 or 4 toxicity when considered in aggregate (86% vs. 40%; p=0.001). Pathologic complete response (pCR) was achieved in 14% of DDP patients versus 3% of standard (p=0.11). 48% of patients in the DDP group were debulked to no residual disease (NRD) versus 28% in the standard group (p=0.16). ConclusionsWhile associated with an increase in severe toxicity compared to standard three-week taxane, DDP appears to facilitate higher rates of pCR and NRD for patients receiving NACT in this preliminary study. These results warrant further investigation of DDP for patients with advanced EOC and assessment of impact on long-term survival outcomes.

158P PET/CT based imaging biomarkers for response prediction of stage IV NSCLC treated with paclitaxel–carboplatin–bevacizumab with or without nitroglycerin

158P PET/CT based imaging biomarkers for response prediction of stage IV NSCLC treated with paclitaxel–carboplatin–bevacizumab with or without nitroglycerin

171P: Carboplatin–paclitaxel bevacizumab followed by the addition of erlotinib to bevacizumab beyond progression in patients with advanced NSCLC

171P: Carboplatin–paclitaxel bevacizumab followed by the addition of erlotinib to bevacizumab beyond progression in patients with advanced NSCLC

Response to chemotherapy with carboplatin plus albumin-bound paclitaxel in a patient with lymphoepithelioma-like thymic carcinoma: A case report.

Thymic carcinoma is a rare neoplasm with a poor outcome due to its aggressive characteristics. For patients who are not operable, radiation therapy and/or palliative chemotherapy are indicated. However, no optimal chemotherapy regimen has been established. The present study reports the case of a 22-year-old man with advanced lymphoepithelioma-like thymic carcinoma refractory to conventional chemotherapy with carboplatin plus solvent-based paclitaxel (sb-PAC) treatment. The patient was subsequently treated with carboplatin plus nanoparticle albumin-bound paclitaxel (nab-PAC). The treatment resulted in a partial response following three cycles of chemotherapy. Since only grade 3 neutropenia, but no other severe adverse effects, was observed, no dose reduction was required. To the best of our knowledge, the current study is the first to present the response to chemotherapy with carboplatin plus nab-PAC in a patient with lymphoepithelioma-like thymic carcinoma. Considering that no standard treatment has been established in thymic carcinoma, nab-PAC may merit further investigation in this rare, but aggressive disease.

Abstract P3-07-13: Homologous recombination deficiency (HRD) as a predictive biomarker of response to preoperative systemic therapy (PST) in TBCRC008 comprising a platinum in HER2-negative primary operable breast cancer

Abstract Background: Biomarkers to predict response to platinum-based therapy in early breast cancer are needed. HRD is a promising predictor of response to DNA damaging agents, such as platinums. We hypothesized that HRD (high HRD score ≥ 42 and/or tumor BRCA [tBRCA] mutation) would predict pathological complete response (pCR) in patients with HER2-negative early breast cancer treated with PST comprising a platinum, regardless of estrogen receptor (ER) status. Methods: TBCRC008 was a multicenter placebo-controlled trial that investigated pCR (no invasive cancer in breast/axilla) following 12 weeks of preoperative carboplatin and albumin-bound paclitaxel with or without vorinostat in patients with ER-positive or triple-negative breast cancer (TNBC) (Connolly RM. JNM 2015). The pCR rate was similar in both arms (vorinostat 25.8%, placebo 29%). We performed an exploratory biomarker study correlating baseline tumor biopsy HRD status with pCR. The analysis population included all patients with available HRD and pCR data. We compared the proportion of patients with pCR by HRD status using Fisher's exact test. A subset analysis compared pCR proportions by high (≥42) vs. low (&amp;lt;42) HRD score in those patients who did not have tBRCA mutation. A logistic regression model included HRD status, ER status, treatment arm, tumor grade and use of additional anthracycline-based non-study chemotherapy prior to definitive surgery. Results: HRD status and pCR data were available for 48/62 patients (30 ER-positive, 18 TNBC). Of these, 46% of tumors were HR deficient (n=22/48, 33% ER-positive [10/30], 67% TNBC [12/18]). We observed a significantly higher pCR rate in patients with HR deficiency vs not (50% vs 7.7%, p=0.002) in the overall population. A similar trend was observed in ER-positive (30% vs 5%, p=0.095) and TNBC (66.7% vs 16.7%, p=0.13) patients. There was no significant difference when analyzed by treatment arm (vorinostat vs placebo). In a subgroup analysis (n=40) of patients without tBRCA (25 ER-positive, 15 TNBC), a significantly higher pCR rate was observed in those with high vs low HRD score (64.3% vs 7.7%, p &amp;lt;0.001). After adjusting for ER status, randomized treatment, use of AC treatment, and tumor grade, patients whose tumors exhibited HR deficiency had a greater than 6 fold increase in pCR compared to those without HR deficiency (adjusted odds ratio = 6.76, 95% CI = 0.85-53.99, p=.072). Conclusion: This is the first study to evaluate the predictive role of HRD status in patients with ER-positive, HER2-negative breast cancer treated with platinum-based therapy. Our results also support prior observations that HRD status is a promising predictive biomarker of response to platinum agents in TNBC. Further evaluation of this question is warranted in both TNBC and ER-positive breast cancer. Citation Format: Connolly R, Elkin E, Timms K, Goetz M, Boughey J, Zhang Z, Walsh B, Carpenter J, Storniolo A, Watkins S, Gabrielson E, Hartman A-R, Stearns V. Homologous recombination deficiency (HRD) as a predictive biomarker of response to preoperative systemic therapy (PST) in TBCRC008 comprising a platinum in HER2-negative primary operable breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-07-13.

Immunosuppressive parameters in serum of ovarian cancer patients change during the disease course

ABSTRACTNeoplastic cells can escape immune control leading to cancer growth. Regulatory T cells (Treg), myeloid-derived suppressor cells (MDSC) and tumor-associated macrophages (TAM) are crucial in immune escape. TAM are divided based on their immune profile, M1 are immunostimulatory while M2 are immunosuppressive. Research so far has mainly focused on the intratumoral behavior of these cells. This study, on the other hand, explored the systemic changes of the key metabolites [IL-4 (interleukin), IL-13, arginase, IL-10, VEGF-A (vascular endothelial growth factor), CCL-2 (chemokine (C-C) motif ligand 2) and TGF-β (transforming growth factor)] linked to Treg, MDSC and TAM during the course of the disease in ovarian and fallopian tube cancer patients. Serum samples were therefore analyzed at diagnosis, after (interval)-debulking surgery and after chemotherapy (paclitaxel–carboplatin). We also determined galectin-1 (gal-1), involved in angiogenesis and tumor-mediated immune evasion. We found significantly lower levels of IL-10, VEGF-A, TGF-β and arginase and higher levels of gal-1 after chemotherapy compared to diagnosis. After debulking surgery, a decrease in IL-10 was significant. Gal-1 and CCL-2 appeared independent prognostic factors for progression-free and overall survival (OS) (multivariate analysis). These results will help us in the decision making of future therapies in order to further modulate the immune system in a positive way.

Abstract C122: A randomized, multicenter, open-label, phase 2 study of paclitaxel-carboplatin (PC) chemotherapy plus necitumumab (IMC-11F8/LY3012211) versus PC alone in the first-line treatment of patients (pts) with stage IV squamous non-small cell lung cancer (sq-NSCLC)

Abstract Background: Necitumumab (N) is a 2nd-generation human IgG1 anti-EGFR monoclonal antibody. In a phase 3 trial (SQUIRE) conducted in the first-line setting, N combined with gemcitabine plus cisplatin improved overall survival (OS) in pts with sq-NSCLC compared with chemotherapy alone. PC, another standard of care was selected for this exploratory phase 2 study. Materials and Methods: Pts with stage IV sq-NSCLC, stratified by ECOG PS (0 vs. 1) and sex (females vs. males) were randomized 2:1and received either PC (P = 200 mg/m2 iv, day 1; C = AUC 6 iv, day 1) plus N (800 mg iv, days 1 and 8) (PC+N arm), or PC alone (PC arm) every 21 days for up to 6 cycles. PC+N pts with a response of stable disease or better continued on N alone until progressive disease or intolerable toxicity. Rash prophylaxis was permitted from the beginning of the trial. The primary endpoint was objective response rate (ORR) based on RECIST 1.1. Secondary endpoints included progression-free survival (PFS), OS, and safety. Sample size and randomization allowed for a 95% confidence interval estimate of ORR for Arm PC+N with a width ≤ 20 percentage points. Final analysis was performed after a minimum of 98 OS events had been observed. No formal hypothesis testing was planned; the study was not powered to show a statistically significant effect for PFS or OS. Results: 167 pts were randomized (n = 110, PC+N; n = 57, PC). Baseline characteristics were balanced between PC+N and PC, respectively, including males (79% and 77%), ECOG PS 0 (16% and 19%), and PS 1 (85% and 81%). Exposure to chemotherapy was similar in both arms; median dose intensity (DI) for P was 98% vs 95% (PC+N vs PC), and DI for C was 100% vs 95%, respectively, and DI for N was 96%. 53% of PC+N pts continued N alone for a median of 4 additional cycles (range 2.0-7.5). The addition of N to PC resulted in an ORR of 48.9% vs 40.0%. Disease control rate was 87.2% vs 84.0% in PC. PFS HR was 1.0 (mPFS 5.4 vs 5.6 months). Median OS was 13.2 vs 11.2 months (HR = 0.83, p = 0.379). There was a higher rate of events for the PC+N arm during the first 4 months, with a later trend toward improved survival after 4 months. Most frequently reported SAEs were pneumonia (12.3% vs. 5.5%) and febrile neutropenia (5.7% vs. 3.6%). Grade ≥3 AEs typically associated with EGFR mAbs that showed a &amp;gt;2% increase were hypomagnesemia (5.7% vs 0) and rash (2.8% vs 0). Any grade venous thromboembolic events occurred in 3.8% of patients in the PC+N group vs 3.6% of patients in the PC group. Infusion related reactions of any grade occurred in 3.8% of patients in the PC+N group vs 9.1% in the PC group. Conclusions: The addition of N to PC resulted in an increased ORR compared to PC alone, indicating an add-on effect. The lower incidence of grade 3 rash observed here (2.8%) versus SQUIRE (7%) may be due to the permission of first cycle rash prophylaxis (SQUIRE no rash prophylaxis permitted prior to cycle 2). The safety profile in this study is consistent with the expected safety profile of an EGFR mAb administered in this combination in the sq-NSCLC population. Clinical trial information: NCT01769391. Citation Format: David Spigel, Alexander Luft, Rodryg Ramlau, Mazen Khalil, Joo-Hang Kim, Carlos Mayo, Henrik Depenbrock, Grace Chao, Coleman Obasaju, Ronald Natale. A randomized, multicenter, open-label, phase 2 study of paclitaxel-carboplatin (PC) chemotherapy plus necitumumab (IMC-11F8/LY3012211) versus PC alone in the first-line treatment of patients (pts) with stage IV squamous non-small cell lung cancer (sq-NSCLC). [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr C122.

Treatment Outcomes of Epithelial Ovarian Cancers Following Maximum Cytoreduction and Adjuvant Paclitaxel-Carboplatin Chemotherapy: Egyptian NCI Experience.

Epithelial ovarian cancer (EOC) is the commonest malignancy involving the ovaries. Maximum surgical cytoreduction (MCR) followed by adjuvant taxane-platinum chemotherapy are the standard of care treatments. To study treatment outcomes of EOC patients that were maximally cyto-reduced and received adjuvant paclitaxel-carboplatin (PC) chemotherapy. This retrospective cohort study included 174 patients with EOC treated at the Egyptian National Cancer Institute between 2006 and 2010. For inclusion, they should have had undergone MCR with no-gross residual followed by adjuvant PC chemotherapy. MCR was total abdominal hysterectomy/bilateral salpingo-oophorectomy [TAH/BSO] or unilateral salpingo- oophorectomy [USO] plus comprehensive staging. The median age was 50 years. Most patients were married (97.1%), had offspring (92.5%), were postmenopausal (53.4%), presented with abdominal/pelvic pain and swelling (93.7%), had tumors involving both ovaries (45.4%) without extra-ovarian extension i.e. stage I (55.2%) of serous histology (79.9%) and grade II (87.4%). TAH/BSO was performed in 97.7% of cases. A total of 1,014 PC chemotherapy cycles were administered and were generally tolerable with 93.7% completing 6 cycles. Alopecia and numbness were the commonest adverse events. The median follow up period was 42 months. The 2-year rates for disease free survival (DFS) and overall survival (OS) were 70.7% and 94.8%, respectively. The respective 5-year rates were 52.6% and 81.3%. Advanced stage and high-grade were significantly associated with poor DFS and OS (p<0.001). Age >65 years was associated with poor OS (p =0.008). Using Cox-regression, stage was independent predictor of poor DFS and OS. Age was an independent predictor of poor OS.

Does Severe Radiation Pneumonitis (RP) Affect Clinical Outcomes in Nonoperable Stage III Non-Small Cell Lung Cancer (NSCLC) Patients Treated With Carboplatin/Paclitaxel (CP)-based Concurrent Chemoradiation Therapy (CRT)?

Does Severe Radiation Pneumonitis (RP) Affect Clinical Outcomes in Nonoperable Stage III Non-Small Cell Lung Cancer (NSCLC) Patients Treated With Carboplatin/Paclitaxel (CP)-based Concurrent Chemoradiation Therapy (CRT)?

A randomized phase II study comparing paclitaxel–carboplatin–bevacizumab with or without nitroglycerin patches in patients with stage IV nonsquamous nonsmall-cell lung cancer: NVALT12 (NCT01171170)

BackgroundNitroglycerin (NTG) increases tumor blood flow and oxygenation by inhibiting hypoxia-inducible-factor (HIF)-1. A randomized phase II study has shown improved outcome when NTG patches were added to vinorelbine/cisplatin in patients with advanced nonsmall-cell lung cancer (NSCLC). In addition, there is evidence that the combination of bevacizumab and HIF-1 inhibitors increases antitumor activity. Patients and methodsIn this randomized phase II trial, chemo-naive patients with stage IV nonsquamous NSCLC were randomized to four cycles of carboplatin (area under the curve 6)–paclitaxel (200mg/m2)–bevacizumab 15mg/kg on day 1 every 3 weeks with or without NTG patches 15mg (day -2 to +2) followed by bevacizumab with or without NTG until progression. Response was assessed every two cycles. Primary end point was progression-free survival (PFS). The study was powered (80%) to detect a decrease in the hazard of tumor progression of 33% at α = 0.05 with a two-sided log-rank test when 222 patients were enrolled and followed until 195 events were observed. ResultsBetween 1 January 2011 and 1 January 2013, a total of 223 patients were randomized; 112 control arm and 111 experimental arm; response rate was 54% in control arm and 38% in experimental arm. Median [95% confidence interval (CI)] PFS in control arm was 6.8 months (5.6–7.3) and 5.1 months (4.2–5.8) in experimental arm, hazard ratio (HR) 1.27 (95% CI 0.96–1.67). Overall survival (OS) was 11.6 months (8.8–13.6) in control arm and 9.4 months (7.8–11.3) in experimental arm, HR 1.02 (95% CI 0.71–1.46). In the experimental arm, no additional toxicity was observed except headache (6% versus 52% in patients treated with NTG). ConclusionAdding NTG to first-line carboplatin–paclitaxel–bevacizumab did not improve PFS and OS in patients with stage IV nonsquamous NSCLC.

Cost-effectiveness analysis of EGFR mutation testing in patients with non-small cell lung cancer (NSCLC) with gefitinib or carboplatin-paclitaxel.

Assess the cost-effectiveness of an EGFR-mutation testing strategy for advanced NSCLC in first-line therapy with either gefitinib or carboplatin-paclitaxel in Mexican institutions. Cost-effectiveness analysis using a discrete event simulation (DES) model to simulate two therapeutic strategies in patients with advanced NSCLC. Strategy one included patients tested for EGFR-mutation and therapy given accordingly. Strategy two included chemotherapy for all patients without testing. All results are presented in 2014 US dollars. The analysis was made with data from the Mexican frequency of EGFR-mutation. A univariate sensitivity analysis was conducted on EGFR prevalence. Progression-free survival (PFS) transition probabilities were estimated on data from the IPASS and simulated with a Weibull distribution, run with parallel trials to calculate a probabilistic sensitivity analysis. PFS of patients in the testing strategy was 6.76months (95% CI 6.10-7.44) vs 5.85months (95% CI 5.43-6.29) in the non-testing group. The one-way sensitivity analysis showed that PFS has a direct relationship with EGFR-mutation prevalence, while the ICER and testing cost have an inverse relationship with EGFR-mutation prevalence. The probabilistic sensitivity analysis showed that all iterations had incremental costs and incremental PFS for strategy 1 in comparison with strategy 2. There is a direct relationship between the ICER and the cost of EGFR testing, with an inverse relationship with the prevalence of EGFR-mutation. When prevalence is>10% ICER remains constant. This study could impact Mexican and Latin American health policies regarding mutation detection testing and treatment for advanced NSCLC.

2748 Assessment of associations between disease stage and toxicity with bevacizumab (BEV) in ICON7, a phase III trial of front-line carboplatin/paclitaxel (CP) ± BEV for ovarian cancer (OC)

2748 Assessment of associations between disease stage and toxicity with bevacizumab (BEV) in ICON7, a phase III trial of front-line carboplatin/paclitaxel (CP) ± BEV for ovarian cancer (OC)

MicroRNA expression profiling predicts clinical outcome of carboplatin/paclitaxel-based therapy in metastatic melanoma treated on the ECOG-ACRIN trial E2603.

BackgroundCarboplatin/paclitaxel (CP), with or without sorafenib, result in objective response rates of 18–20 % in unselected chemotherapy-naïve patients. Molecular predictors of survival and response to CP-based chemotherapy in metastatic melanoma (MM) are critical to improving the therapeutic index.Intergroup trial E2603 randomized MM patients to CP with or without sorafenib. Expression data were collected from pre-treatment formalin-fixed paraffin-embedded (FFPE) tumor tissues from 115 of 823 patients enrolled on E2603. The selected patients were balanced across treatment arms, BRAF status, and clinical outcome. We generated data using Nanostring array (microRNA (miRNA) expression) and DNA-mediated annealing, selection, extension and ligation (DASL)/Illumina microarrays (HT12 v4) (mRNA expression) with protocols optimized for FFPE samples. Integrative computational analysis was performed using a novel Tree-guided Recursive Cluster Selection (T-ReCS) [1] algorithm to select the most informative features/genes, followed by TargetScan miRNA target prediction (Human v6.2) and mirConnX [2] for network inference.ResultsT-ReCS identified PLXNB1 as negatively associated with progression-free survival (PFS) and miR-659-3p as the primary miRNA associated positively with PFS. miR-659-3p was differentially expressed based on PFS but not based on treatment arm, BRAF or NRAS status. Dichotomized by median PFS (less vs greater than 4 months), miR-659-3p expression was significantly different. High miR-659-3p expression distinguished patients with responsive disease (complete or partial response) from patients with stable disease. miR-659-3p predicted gene targets include NFIX, which is a transcription factor known to interact with c-Jun and AP-1 in the context of developmental processes and disease.ConclusionsThis novel integrative analysis implicates miR-659-3p as a candidate predictive biomarker for MM patients treated with platinum-based chemotherapy and may serve to improve patient selection.