Carboplatin Paclitaxel Research Articles

Adjuvant chemoradiotherapy versus radiotherapy alone for women with high-risk endometrial cancer (PORTEC-3): final results of an international, open-label, multicentre, randomised, phase 3 trial

SummaryBackgroundAlthough women with endometrial cancer generally have a favourable prognosis, those with high-risk disease features are at increased risk of recurrence. The PORTEC-3 trial was initiated to investigate the benefit of adjuvant chemotherapy during and after radiotherapy (chemoradiotherapy) versus pelvic radiotherapy alone for women with high-risk endometrial cancer.MethodsPORTEC-3 was an open-label, international, randomised, phase 3 trial involving 103 centres in six clinical trials collaborating in the Gynaecological Cancer Intergroup. Eligible women had high-risk endometrial cancer with FIGO 2009 stage I, endometrioid-type grade 3 with deep myometrial invasion or lymph-vascular space invasion (or both), endometrioid-type stage II or III, or stage I to III with serous or clear cell histology. Women were randomly assigned (1:1) to receive radiotherapy alone (48·6 Gy in 1·8 Gy fractions given on 5 days per week) or radiotherapy and chemotherapy (consisting of two cycles of cisplatin 50 mg/m2 given during radiotherapy, followed by four cycles of carboplatin AUC5 and paclitaxel 175 mg/m2) using a biased-coin minimisation procedure with stratification for participating centre, lymphadenectomy, stage of cancer, and histological type. The co-primary endpoints were overall survival and failure-free survival. We used the Kaplan-Meier method, log-rank test, and Cox regression analysis for final analysis by intention to treat and adjusted for stratification factors. The study was closed on Dec 20, 2013, after achieving complete accrual; follow-up is ongoing. PORTEC-3 is registered with ISRCTN, number ISRCTN14387080, and ClinicalTrials.gov, number NCT00411138.Results686 women were enrolled between Nov 23, 2006, and Dec 20, 2013. 660 eligible patients were included in the final analysis, of whom 330 were assigned to chemoradiotherapy and 330 were assigned to radiotherapy. Median follow-up was 60·2 months (IQR 48·1–73·1). 5-year overall survival was 81·8% (95% CI 77·5–86·2) with chemoradiotherapy versus 76·7% (72·1–81·6) with radiotherapy (adjusted hazard ratio [HR] 0·76, 95% CI 0·54–1·06; p=0·11); 5-year failure-free survival was 75·5% (95% CI 70·3–79·9) versus 68·6% (63·1–73·4; HR 0·71, 95% CI 0·53–0·95; p=0·022). Grade 3 or worse adverse events during treatment occurred in 198 (60%) of 330 who received chemoradiotherapy versus 41 (12%) of 330 patients who received radiotherapy (p<0·0001). Neuropathy (grade 2 or worse) persisted significantly more often after chemoradiotherapy than after radiotherapy (20 [8%] women vs one [1%] at 3 years; p<0·0001). Most deaths were due to endometrial cancer; in four patients (two in each group), the cause of death was uncertain. One death in the radiotherapy group was due to either disease progression or late treatment complications; three deaths (two in the chemoradiotherapy group and one in the radiotherapy group) were due to either intercurrent disease or late treatment-related toxicity.InterpretationAdjuvant chemotherapy given during and after radiotherapy for high-risk endometrial cancer did not improve 5-year overall survival, although it did increase failure-free survival. Women with high-risk endometrial cancer should be individually counselled about this combined treatment. Continued follow-up is needed to evaluate long-term survival.FundingDutch Cancer Society, Cancer Research UK, National Health and Medical Research Council Project Grant and Cancer Australia, L'Agenzia Italiana del Farmaco, and Canadian Cancer Society Research Institute.

Systemic immune signature of inflammation in metastatic melanoma (MM) patients treated with ipilimumab (IPI) and carboplatin/paclitaxel (CP).

185 Background: Only a subset of MM patients benefit from treatment with IPI. In an effort to increase response and identify predictive immune biomarkers, we combined IPI with CP. We here report a significant correlation between overall survival (OS) and biomarkers of a pre-existing inflammatory state. Methods: 30 patients were treated with C (AUC = 6) and P (175mg/m2) every 3 weeks x 5 and IPI (3mg/kg) every 3 weeks x 4. Blood was collected throughout. OS Kaplan–Meier curves were compared by the log-rank test. Cutoff thresholds defining high or low levels of chemokines, B cell populations and PD-1+CD8+ T cell populations were established from the mean value of a given variable from all patients. Neutrophil to Lymphocyte Ratio (NLR) and Systemic Immune Inflammation Index defined as Platelet x Neutrophil to Lymphocyte Ratio (SII) were calculated at baseline and tested for association with OS. SII ≥ 1375 and NLR ≥ 5 were considered as high risk groups. Results: Median OS was 16.2 months, with a 3-year OS of 36.7% for all patients. High levels of CCL3 (HR = 2.79, p = 0.0159), CCL4 (HR = 8.36, p &lt; 0.0001) and CXCL8 (HR = 3.52, p = 0.0037) were associated with worse OS. Advanced B cell differentiation before treatment was associated with worse patient outcomes. High levels of early differentiated Bm2 ( &gt; 57%) were strongly associated with better OS: HR = 0.26 p = 0.004 whereas high eBm5+Bm5 ( &gt; 14%) levels were strongly associated with worse OS: HR = 2.65, p = 0.029. Patients with higher proportions of PD-1+CD8+ T cells in circulation during treatment had poorer OS (HR = 3.84, p = 0.004) at week 10; (HR = 3.53, p = 0.005) at week 13 and (HR = 2.84, p = 0.040) at week 24. High risk SII (HR = 3.30, p = 0.0192) and NLR (HR = 2.367, p = 0.0486) were associated with worse OS. Conclusions: We have identified a significant correlation between pre-existing systemic inflammatory state and a poor response to IPI and CP. Specifically elevated CCL3, CCL4 and CXCL8, baseline B lymphocyte subset skewing, increased CD8+PD-1+ T lymphocytes, increased NLR and SII were all strongly associated to worse OS. Comprehensive immune monitoring provides evidence for new circulating biomarkers predicting outcome in MM patients treated with IPI and CP. Clinical trial information: NCT01676649.

Clinical consequences of upfront pathology review in the randomised PORTEC-3 trial for high-risk endometrial cancer

BackgroundIn the PORTEC-3 trial, women with high-risk endometrial cancer (HR-EC) were randomised to receive pelvic radiotherapy (RT) with or without concurrent and adjuvant chemotherapy (two cycles of cisplatin 50 mg/m2 in weeks 1 and 4 of RT, followed by four cycles of carboplatin AUC5 and paclitaxel 175 mg/m2). Pathology review was required before patient enrolment. The aim of this analysis was to evaluate the role of central pathology review before randomisation.Patients and methodsA total of 1295 cases underwent pathology review to confirm HR-EC in the Netherlands (n = 395) and the UK (n = 900), and for 1226/1295 (95%) matching review and original reports were available. In total, 329 of these patients were enrolled in the PORTEC-3 trial: 145 in the Netherlands and 184 in the UK, comprising 48% of the total PORTEC-3 cohort of 686 participants. Areas of discrepancies were evaluated, and inter-observer agreement between original and review opinion was evaluated by calculating the kappa value (κ).ResultsIn the 1226 pathology reviews, 6356 selected items were evaluable for both original and review pathology. In 43% of cases at least one pathology item changed after review. For 102 patients (8%), this discrepancy led to ineligibility for the PORTEC-3 trial, most frequently due to differences in the assessment of histological type (34%), endocervical stromal involvement (27%) and histological grade (19%). Lowest inter-observer agreement was found for histological type (κ = 0.72), lymph-vascular space invasion (κ = 0.72) and histological grade (κ = 0.70).ConclusionCentral pathology review by expert gynaeco-pathologists changed histological type, grade or other items in 43% of women with HR-EC, leading to ineligibility for the PORTEC-3 trial in 8%. Upfront pathology review is essential to ensure enrolment of the target trial-population, and to avoid over- or undertreatment, especially when treatment modalities with substantial toxicity are involved.This study is registered with ISRCTN (ISRCTN14387080, www.controlled-trials.com) and with ClinicalTrials.gov (NCT00411138).

DIFFERENCE IN BLOOD FUNCTION TOXICITY BETWEEN STADIUM IIB-IIIB SQUAMOUS CELL CERVICAL CANCER PATIENTS WITH PACLITAXEL CISPLATIN AND PACLITAXEL CARBOPLATIN CHEMOTHERAPY AT SANGLAH HOSPITAL, DENPASAR.

Objective: Paclitaxel cisplatin and paclitaxel carboplatin were chemotherapy regimens used for cervical cancer treatments at Sanglah Hospital, Denpasar. They came with hematologic toxicity side effects. This could be monitored from hemoglobin, thrombocyte, and leukocyte parameter. Data that compared the toxicity of these two regimens were still limited at Sanglah Hospital, Denpasar. Therefore, it was necessary to conduct a research about the difference in blood function toxicity between patients who underwent paclitaxel cisplatin chemotherapy and those who underwent paclitaxel carboplatin chemotherapy based on those three parameters.Methods: This was a prospective observational research with consecutive sampling, inclusion, and exclusion criteria. It was carried out from January to August 2016 at Sanglah Hospital, Denpasar. Patients were categorized into two groups based on their chemotherapy regimens. Next, blood samples from both groups were tested for its hemoglobin, thrombocyte, and leukocyte level before and after chemotherapy. The data underwent normality test using either Shapiro–Wilk or Mann–Whitney test with SPSS.Results: There were 17 patients who fulfilled the inclusion criteria. The result showed a decrease in hemoglobin, thrombocyte, as well as leukocyte values in patients who underwent paclitaxel cisplatin and paclitaxel carboplatin chemotherapy.Conclusion: The decrease of both hemoglobin and leukocyte level was not meaningful in both groups (p&gt;0.05). Meanwhile, the decrease of thrombocyte level was meaningful in both groups (*p&lt;0.05) in which patients who belong to paclitaxel carboplatin chemotherapy group showed a higher decrease of thrombocyte values.

DIFFERENCE IN BLOOD FUNCTION TOXICITY BETWEEN STADIUM IIB-IIIB SQUAMOUS CELL CERVICAL CANCER PATIENTS WITH PACLITAXEL CISPLATIN AND PACLITAXEL CARBOPLATIN CHEMOTHERAPY AT SANGLAH HOSPITAL, DENPASAR.

Objective: Paclitaxel cisplatin and paclitaxel carboplatin were chemotherapy regimens used for cervical cancer treatments at Sanglah Hospital, Denpasar. They came with hematologic toxicity side effects. This could be monitored from hemoglobin, thrombocyte, and leukocyte parameter. Data that compared the toxicity of these two regimens were still limited at Sanglah Hospital, Denpasar. Therefore, it was necessary to conduct a research about the difference in blood function toxicity between patients who underwent paclitaxel cisplatin chemotherapy and those who underwent paclitaxel carboplatin chemotherapy based on those three parameters.Methods: This was a prospective observational research with consecutive sampling, inclusion, and exclusion criteria. It was carried out from January to August 2016 at Sanglah Hospital, Denpasar. Patients were categorized into two groups based on their chemotherapy regimens. Next, blood samples from both groups were tested for its hemoglobin, thrombocyte, and leukocyte level before and after chemotherapy. The data underwent normality test using either Shapiro–Wilk or Mann–Whitney test with SPSS.Results: There were 17 patients who fulfilled the inclusion criteria. The result showed a decrease in hemoglobin, thrombocyte, as well as leukocyte values in patients who underwent paclitaxel cisplatin and paclitaxel carboplatin chemotherapy.Conclusion: The decrease of both hemoglobin and leukocyte level was not meaningful in both groups (p&gt;0.05). Meanwhile, the decrease of thrombocyte level was meaningful in both groups (*p&lt;0.05) in which patients who belong to paclitaxel carboplatin chemotherapy group showed a higher decrease of thrombocyte values.

A prospective study of radiation-induced hypothyroidism in head and neck cancer patients

Background: Head and neck cancers are one of the most common cancers worldwide. Radiotherapy is the only curative treatment, besides surgery. The most common clinical late effect of thyroid gland irradiation in patients exposed to therapeutic doses to the neck is hypothyroidism, and hypothyroidism causes morbidity and mortality if untreated. There is not enough data about post-radiotherapy hypothyroidism in head and neck cancer patients in eastern India. Objectives: The purpose of our study is to identify the incidence of hypothyroidism following radiotherapy in head and neck cancer patients in eastern India and to assess the time period for the development of hypothyroidism for early treatment to reduce hypothyroid related morbidity and mortality. Materials and Methods: The study was done in 107 histopathologically proved head and neck cancer patients between June 2013 and May 2016. Patients were treated with Cobalt 60 Teletherapy machine with conventional fractionation. 31 (28.9%) patients received concurrent chemoradiation with weekly Cisplatin, 50 (46.7%) patients received radiation alone, and 26 (24.3%) patients received neo-adjuvant chemotherapy with injection Paclitaxel and injection Carboplatin followed by radiation. Results: Male patients were 80 (74.8%) and 27 (25.2 %) were female patients, and the age groups were 42–70 years, and the median age was 52 years. Primary tumor in the majority of the patients was carcinoma larynx 51 (47.6%). At 36 months of follow-up 13 (25%), patients were to have subclinical hypothyroidism, 9 (17.3%) patients were to have clinical hypothyroidism, and percentage of hypothyroidism was 42.3%. The first occurrence of hypothyroidism was seen over a follow-up period of 6 months in our study. Conclusion: It is recommended that serum thyroid stimulating hormone and free T4 have been estimated before initiation of radiotherapy and post radiotherapy at regular interval 6–12 months and carried out lifelong and physicians should not neglect to evaluate thyroid function of post-radiotherapy head and neck cancer patients.

Peripheral and local predictive immune signatures identified in a phase II trial of ipilimumab with carboplatin/paclitaxel in unresectable stage III or stage IV melanoma

BackgroundCheckpoint blockade with ipilimumab provides long-term survival to a significant proportion of patients with metastatic melanoma. New approaches to increase survival and to predict which patients will benefit from treatment are needed. This phase II trial combined ipilimumab with carboplatin/paclitaxel (CP) to assess its safety, efficacy, and to search for peripheral and tumor-based predictive biomarkers.MethodsThirty patients with untreated unresectable/metastatic melanoma were treated with ipilimumab and CP. Adverse events (AEs) were monitored and response to treatment was evaluated. Tumor tissue and peripheral blood were collected at specified time points to characterize tumor immune markers by immunohistochemistry and systemic immune activity by multiplex assays and flow cytometry.ResultsEighty three percent of patients received all 5 cycles of CP and 93% completed ipilimumab induction. Serious AEs occurred in 13% of patients, and no treatment-related deaths were observed. Best Overall Response Rate (BORR) and Disease Control Rate (DCR) were 27 and 57%, respectively. Median overall survival was 16.2 months. Response to treatment was positively correlated with a higher tumor CD3+ infiltrate (immune score) at baseline. NRAS and BRAF mutations were less frequent in patients who experienced clinical benefit. Assessment of peripheral blood revealed that non-responders had elevated baseline levels of CXCL8 and CCL4, and a higher proportion of circulating late differentiated B cells. Pre-existing high levels of chemokines (CCL3, CCL4 and CXCL8) and advanced B cell differentiation were strongly associated with worse patient overall survival. Elevated proportions of circulating CD8+/PD-1+ T cells during treatment were associated with worse survival.ConclusionsThe combination of ipilimumab and CP was well tolerated and revealed novel characteristics associated with patients likely to benefit from treatment. A pre-existing systemic inflammatory state characterized by elevation of selected chemokines and advanced B cell differentiation, was strongly associated with poor patient outcomes, revealing potential predictive circulating biomarkers.Trial registrationClinicaltrials.gov, NCT01676649, registered on August 29, 2012.

DIFFERENCE OF TUMOR MASS IN STADIUM IIB-IIIB SQUAMOUS CELL CERVICAL CANCER PATIENTS WHO UNDERWENT PACLITAXEL CISPLATIN AND PACLITAXEL CARBOPLATIN CHEMOTHERAPY AT SANGLAH HOSPITAL DENPASAR

Objective: One of the parameters to measure the efficacy of the use of platinum based chemotherapy was the difference of tumor mass. Unfortunately, there was limited data about the use of rational chemotherapy medicine for cervical cancer patients at Sanglah Hospital. Therefore, research to find more data about the difference of tumor mass was necessary. Method: A prospective observational research conducted at Sanglah Hospital from January until August 2016 by using consecutive sampling method. Patients qualified for the inclusive criteria were separated into two groups, paclitaxel cisplatin and paclitaxel carboplatin. Tumor mass data was gathered from before chemotherapy I and after chemotherapy VI by using USG 2D LOGIQ V5. Data analysed was performed with SPSS 20.0 for windows with a 95% confidence level using Wilcoxon test and Mann Whitney test.Result: The mean value of tumor mass for patients in paclitaxel cisplatin regimen group before chemotherapy I and after chemotherapy VI were 68.91+7.41 cm3 and 10.62+6.82 cm3 respectively (p value=0.018). The mean value of tumor mass for patients in paclitaxel carboplatin regimen group before chemotherapy I and after chemotherapy VI were 53.44+52.25 cm3 and 9.18 + 8.23 cm3 respectively (p value=0.007). Meanwhile, the mean value of difference in tumor mass in paclitaxel cisplatin and paclitaxel carboplatin group was -58.29 + 49.93 cm3 and -44.26 + 51.48 cm3 respectively (p value=0.242). Conclusion: This research shows that there was a significant difference of tumor mass before chemotherapy I and chemotherapy VI in both regimen groups. There was a bigger decrease of tumor mass in patients from paclitaxel cisplatin chemotherapy group compared to paclitaxel carboplatin group, but not significantly different.

MTE 22.02 Treatment Options in Advanced Non-Small Cell Lung Cancer (NSCLC) in the Elderly: An Evolving Landscape

MTE 22.02 Treatment Options in Advanced Non-Small Cell Lung Cancer (NSCLC) in the Elderly: An Evolving Landscape

Front-line therapy of advanced epithelial ovarian cancer: standard treatment

Paclitaxel and carboplatin combination chemotherapy has remained the standard of care in the front-line therapy of advanced epithelial ovarian cancer during the last decade. Maintenance chemotherapy has not been proven to impact on overall survival. Acceptable alternatives include weekly paclitaxel plus 3-weekly carboplatin, the addition of bevacizumab to 3-weekly carboplatin and paclitaxel, and intraperitoneal chemotherapy. In particular, anti-angiogenic therapy has been identified as the most promising targeted therapy, and the addition of bevacizumab to first-line chemotherapy followed by a maintenance period of bevacizumab in monotherapy has shown to prolong progression-free survival. This was considered the proof of concept of the value of anti-angiogenic therapy in the front-line of ovarian cancer, and the results of two additional clinical trials with anti-angiogenic tyrosine kinase inhibitors have shown results in the same direction.

THE EFFICACY AND SAFETY OF CARBOPLATIN AND WEEKLY PACLITAXEL COMBINATION THERAPY FOR PREVIOUSLY TREATED SMALL CELL LUNG CANCER PATIENTS WITH INTERSTITIAL LUNG DISEASE

RespirologyVolume 22, Issue S3 p. 75-75 Lung Cancer 3 THE EFFICACY AND SAFETY OF CARBOPLATIN AND WEEKLY PACLITAXEL COMBINATION THERAPY FOR PREVIOUSLY TREATED SMALL CELL LUNG CANCER PATIENTS WITH INTERSTITIAL LUNG DISEASE First published: 23 November 2017 https://doi.org/10.1111/resp.13206_178Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume22, IssueS3Supplement: 22nd Congress of the Asian Pacific Society of Respirology, International Convention Centre, Sydney, Australia, 23–26 November 2017November 2017Pages 75-75 RelatedInformation

THE EFFECT OF CARBOPLATIN PACLITAXEL AND BEVACIZUMAB FOR ADVANCED NON‐SMALL CELL LUNG CANCER WITH MALIGNANT PLEURAL EFFUSION

RespirologyVolume 22, Issue S3 p. 116-116 APSR Poster Abstracts THE EFFECT OF CARBOPLATIN PACLITAXEL AND BEVACIZUMAB FOR ADVANCED NON-SMALL CELL LUNG CANCER WITH MALIGNANT PLEURAL EFFUSION First published: 23 November 2017 https://doi.org/10.1111/resp.13207_81Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume22, IssueS3Supplement: 22nd Congress of the Asian Pacific Society of Respirology, International Convention Centre, Sydney, Australia, 23–26 November 2017November 2017Pages 116-116 RelatedInformation

Shifting Practice in Definitive Chemoradiation for Localized Esophageal Cancer

The efficacy of carboplatin-paclitaxel in the trimodality setting was demonstrated in the cross trial. Because of better tolerance, that regimen has been adopted as an alternative for patients receiving definitive chemoradiation (dcrt). The purpose of our study was to compare outcomes in patients with localized esophageal and gastroesophageal junction (gej) cancer who received dcrt using either platinum-5-fluorouracil (5fu) or carboplatin-paclitaxel. Medical records and outcomes for all patients diagnosed with localized carcinoma of the esophagus and gej at our centre between 2008 and 2015 were reviewed. All patients who underwent dcrt using cisplatin-5fu, carboplatin-5fu, or carboplatin-paclitaxel were included. The 73 identified patients (34 cisplatin-5fu, 13 carboplatin-5fu, 26 carboplatin-paclitaxel) were all prescribed concomitant radiotherapy of 50 Gy in 25 daily fractions. The diagnosis was adenocarcinoma in 64% and squamous cell carcinoma in 36%. Median overall survival (os) duration for the cisplatin-5fu group was 28 months [95% confidence interval (ci): 19 to 41 months], with a 3-year os rate of 44%, in contrast to the 15 months (95% ci: 11 to 17 months) and 15% in the carboplatin-paclitaxel group (log-rank p = 0.0047). Median os duration for the carboplatin-5fu group was 17 months (95% ci: 11 to 68 months) with a 3-year os rate of 31%. Adjusting for patient and disease factors, better os durations and rates were associated with cisplatin-5fu (hazard ratio: 0.34; p = 0.0016) and carboplatin-5fu (hazard ratio: 0.55; p = 0.20) than with carboplatin-paclitaxel. In a dcrt regimen, a better os is associated with cisplatin-5fu than with carboplatin-paclitaxel. Clinical trials to determine optimal chemotherapy regimens are warranted for patients who are not suitable for surgery.

Final Results of a Prospective Phase 2 Study of Adding Erlotinib to Chemoradiation for patients With Stage III Non–small Cell Lung Cancer

Concurrent chemoradiotherapy is the standard of care for inoperable stage III non-small cell lung cancer (NSCLC) patients. We explored if adding erlotinib would increase the effectiveness of chemoradiotherapy, since we have demonstrated radiation sensitization by erlotinib in preclinical setting using mice model. 48 patients with stage III NSCLC, PS 0-1, received radiotherapy (63 Gy/35 fractions) on Monday‒Friday, with chemotherapy (paclitaxel 45 mg/m2, carboplatin AUC=2) on Mondays, for 7 weeks. All patients also received EGFR-TKI erlotinib (150 mg orally 1/day) on Tuesday–Sunday for 7 weeks followed by consolidation paclitaxel–carboplatin. The primary endpoint was time to progression; secondary endpoints were overall survival (OS), toxicity, response, and disease control and whether any endpoint differed by EGFR mutation status. 46 out of 48 patients were evaluable for response, 40 were former or never smoker and 41 were evaluated for EGFR mutation status: 37 wild-type and 4 were found to have mutation ( 3 exon 19 deletion, 1 exon 21 mutation) .Median time to progression was 14 months and did not differ based on EGFR mutation status. Toxicity was acceptable no grade 5 toxicity, I grade 4, and 11 grade 3). Twelve (26%) had complete responses ( 10 with wild type (wt) and 2 with mutation (mt)and 1 unknown).At 73.5 months median follow-up (range 46.2 - 93.7months), 2 and 5 year OS rates were 67.4 % and 36.25%, although there were no significant difference by mutation status. Twelve patients had no progression and 34 had local and/or distant metastasis. All 4 patients with EGFR mutation had local control. Eleven of 27 patients failed in the brain (7 wt, 3 mt and I unkown). Toxicity was acceptable and OS were promising, but time to progression did not meet expectations. The prevalence of distant failures underscores the need for effective systemic therapy. Those patients with EGFR mutation might need induction erlotinib followed by local treatment when they will fail locally in the lung or brain metastasis which is fairly frequent among EGFR mutated patients.

The safety and efficacy of carboplatin plus nanoparticle albumin-bound paclitaxel in the treatment of non-small cell lung cancer patients with interstitial lung disease.

The optimal chemotherapy regimen for non-small cell lung cancer patients with interstitial lung disease is unclear. We therefore investigated the safety and efficacy of carboplatin plus nab-paclitaxel as a first-line regimen for non-small cell lung cancer in patients with interstitial lung disease. We retrospectively reviewed advanced non-small cell lung cancer patients with interstitial lung disease who received carboplatin plus nab-paclitaxel as a first-line chemotherapy regimen at Hyogo Cancer Center between February 2013 and August 2016. interstitial lung disease was diagnosed according to the findings of pretreatment chest high-resolution computed tomography. Twelve patients were included (male, n = 11; female, n = 1). The overall response rate was 67% and the disease control rate was 100%. The median progression free survival was 5.1 months (95% CI: 2.9-8.3 months) and the median overall survival was 14.9 months (95% CI: 4.8-not reached). A chemotherapy-related acute exacerbation of interstitial lung disease was observed in one patient; the extent of this event was Grade 2. There were no treatment-related deaths. Carboplatin plus nab-paclitaxel, as a first-line chemotherapy regimen for non-small cell lung cancer, showed favorable efficacy and safety in patients with preexisting interstitial lung disease.

Tumor and serum DNA methylation in women receiving preoperative chemotherapy with or without vorinostat in TBCRC008

Methylated gene markers have shown promise in predicting breast cancer outcomes and treatment response. We evaluated whether baseline and changes in tissue and serum methylation levels would predict pathological complete response (pCR) in patients with HER2-negative early breast cancer undergoing preoperative chemotherapy. The TBCRC008 trial investigated pCR following 12weeks of preoperative carboplatin and albumin-bound paclitaxel+vorinostat/placebo (n=62). We measured methylation of a 10-gene panel by quantitative multiplex methylation-specific polymerase chain reaction and expressed results as cumulative methylation index (CMI). We evaluated association between CMI level [baseline, day 15 (D15), and change] and pCR using univariate and multivariable logistic regression models controlling for treatment and hormone receptor (HR) status, and performed exploratory subgroup analyses. In univariate analysis, one log unit increase in tissue CMI levels at D15 was associated with 40% lower chance of obtaining pCR (odds ratio, OR0.60, 95% CI 0.37-0.97; p=0.037). Subgroup analyses suggested a significant association between tissue D15 CMI levels and pCR in vorinostat-treated [OR 0.44 (0.20, 0.93), p=0.03], but not placebo-treated patients. In this study investigating the predictive roles of tissue and serum CMI levels in patients with early breast cancer for the first time, we demonstrate that high D15 tissue CMI levels may predict poor response. Larger studies and improved analytical procedures to detect methylated gene markers in early stage breast cancer are needed. TBCRC008 is registered on ClinicalTrials.gov (NCT00616967).

947P - Circulating tumor cells as prognostic marker in ovarian carcinoma: Results from the ANTHALYA study

Background: Circulating tumor cells (CTC) are detected in 12–30% of advanced stage/relapsing ovarian carcinoma (OC). We evaluated the prognostic value of CTC counts among patients (pts) from the ANTHALYA trial, an open-label randomized phase II study evaluating addition of bevacizumab (Beva) to neoadjuvant carboplatin-paclitaxel (CP) in first line for pts with unresectable FIGO stage IIIc/IV ovarian, tubal or peritoneal adenocarcinoma. Methods: We obtained CTC counts at baseline and before interval debulking surgery (IDS). A CTC threshold of ≥ 1 CTC/7.5 mL blood was considered as CTC+. We assessed the prognostic impact of CTCs on objective response rate (ORR), interval debulking surgery (IDS) rate, complete resection rate and progression-free survival (PFS), and explored their potential predictive impact on ORR and PFS according to bevacizumab therapy. Results: In 88 pts with an available CTC count at baseline, CTC+ pts (n = 29) had a 75.9% ORR (at IDS), vs 59.3% for pts with 0 CTC (n = 59): OR = 2.2 [0.8-5.8] (OR-adj=1.8 [0.8-5.8]). Respectively, 58.6% vs 66.1% were amenable to IDS and 55.2% vs 54.2% achieved a complete resection. Median PFS was 21 m [15.0-25.4] in CTC+ pts and 25.8 m [18.5-27.2] in pts with 0 CTC (HR = 1.5 [0.8-2.8] and HR-adj=1.7 [0.9-3.2]). CTC counts at IDS were available in 70 pts. At IDS, a complete resection was achieved in 66.7% of CTC+ pts (n = 6), and in 68.8% of pts with 0 CTC (n = 64). Exploration of the potential predictive impact of CTC is described in the table.Table947PPrognostic approach0 CTC at baseline (n = 59)CTC+ at baseline (n = 29)ORR at IDS59.3%75.9%Median PFS [95% CI]25.8 m [18.5-27.2]21.0 m [15.0-25.4]Predictive approachBeva (n = 36)CP (n = 23)Beva (n = 17)CP (n = 12)ORR at IDS61.1%56.5%82.4%66.7%Median PFS [95% CI]25.8 [20.9-NE]20.3 [13.8-27.2]21.0 [15.0-30.6]20.6 [8.0-25.4]Progression rate at M3636.1%56.5%52.9%83.3% Open table in a new tab Conclusions: Baseline CTC counts in OC patients receiving neoadjuvant chemotherapy +/- bevacizumab carry dual prognostic information: CTC count at IDS do not add any information, CTC+ seems to be associated with a higher ORR, while 0 CTC count seems to be a prognostic factor with better PFS, in the whole population and among patients treated with bevacizumab. Clinical trial identification: 2012-01144-22 Legal entity responsible for the study: ROCHE Funding: Roche Disclosure: T. de La Motte Rouge: Consultancy work: AstraZeneca, Roche, MSD, Eisai, Sanofi Travel grants/meeting support: Roche, Novartis, Pfizer Corporate-sponsored research: Novartis. P. Cottu: Novartis, Roche, AstraZeneca, Nanostring, Pfizer. P. Pautier: Membership on an advisory board or board of directors: Roche: Travel grants/meeting support: Roche, Astra Zeneca, Pharmamar Corporate-sponsored research; Pharmamar, Novartis. A. Floquet: Membership on an advisory board or board of directors: Roche, AstraZeneca; Travel grants/meeting support: Roche, AstraZeneca. F. Selle: Consultancy work: Roche: Travel grants/meeting support: Roche, AstraZeneca, Pharmamar. M. Fabbro: Travel grants/meeting support: Roche. E. Kalbacher: Travel grants/meeting support: Roche, Pharmamar, GSK, Leo Pharma, AstraZeneca. P. Follana: Consultancy work: AstraZeneca, Novartis Travel grants/meeting support: Roche, AstraZeneca, Amgen. A.F. Lesoin: Employment: Centre Oscar Lambret, Lille. J. Medioni: Membership on an advisory board or board of directors: AstraZeneca, Pierre Fabre Consultancy work: Clovis Oncology; Travel grants/meeting support: Roche, Sanofi Aventis. J. Dupin: Employment: Roche. R-M. Ferri: Employment: Roche SAS. C. Dubot: Corporate-sponsored research: Roche. R. Rouzier: Membership on an advisory board or board of directors: Roche; Consultancy work: Roche; Travel grants/meeting support: Roche; Corporate-sponsored research: Roche. F. Joly Lobbedez: Consultancy work: AstraZeneca, Janssen, Tesaro, Roche, Sanofi, Novartis, Bristol-Myers Squib Travel grants/meeting support: Roche, Janssen, AstraZeneca, Tesaro Corporate-sponsored research: Astellas, Janssen. All other authors have declared no conflicts of interest.

Evaluation of Natriuretic Peptide in Non-small Cell Lung Cancer Patients Treated with Bevacizumab Together with Carboplatin-Paclitaxel: A Prospective Study.

To identify predictive markers for efficacy of combination bevacizumab and carboplatin-paclitaxel treatment in patients with advanced non-squamous non-small cell lung cancer (NSCLC). Twenty patients received carboplatin (area under the concentration-time curve (AUC) 6 mg/ml×min) and paclitaxel (200 mg/m2) with bevacizumab (15 mg/kg) on day 1 of a 21-day cycle. After four cycles of induction therapy, patients received bevacizumab maintenance therapy until disease progression or unacceptable toxicity occurred. Plasma and serum samples (baseline, day 8 and before cycle 2) were analyzed for natriuretic peptide content. Plasma brain natriuretic peptide (BNP) levels were significantly decreased at day 8 (20.1±4.0 pg/ml vs. 9.1±1.8 pg/ml, p=0.0002). Patients whose plasma BNP level was reduced to <50% of the baseline at day 8 had a longer progression-free survival (PFS) than those with a less decrease (9.73 versus 2.63 months, p=0.00013). In multivariate Cox analysis, decrease of plasma BNP concentration was associated with a longer PFS (p=0.0022). Decrease of plasma BNP concentration correlated with PFS after a treatment of combination bevacizumab plus carboplatin-paclitaxel.

Kinase-driven metabolic signalling as a predictor of response to carboplatin\u2013paclitaxel adjuvant treatment in advanced ovarian cancers

Background:The biological mechanisms underlying early- and advanced-stage epithelial ovarian cancers (EOCs) are still poorly understood. This study explored kinase-driven metabolic signalling in early and advanced EOCs, and its role in tumour progression and response to carboplatin–paclitaxel treatment.Methods:Tumour epithelia were isolated from two independent sets of primary EOC (n=72 and 30 for the discovery and the validation sets, respectively) via laser capture microdissection. Reverse phase protein microarrays were used to broadly profile the kinase-driven metabolic signalling of EOC with particular emphasis on the LBK1–AMPK and AKT–mTOR axes. Signalling activation was compared between early and advanced lesions, and carboplatin–paclitaxel-sensitive and -resistant tumours.Results:Advanced EOCs were characterised by a heterogeneous kinase-driven metabolic signature and decreased phosphorylation of the AMPK–AKT–mTOR axis compared to early EOC (P<0.05 for AMPKα T172, AMPKα1 S485, AMPKβ1 S108, AKT S473 and T308, mTOR S2448, p70S6 S371, 4EBP1 S65, GSK-3 α/β S21/9, FOXO1 T24/FOXO3 T32, and FOXO1 S256). Advanced tumours with low relative activation of the metabolic signature and increased FOXO1 T24/FOXO3 T32 phosphorylation (P=0.041) were associated with carboplatin–paclitaxel resistance.Conclusions:If validated in a larger cohort of patients, the decreased AMPK–AKT–mTOR activation and phosphorylation of FOXO1 T24/FOXO3 T32 may help identify carboplatin–paclitaxel-resistant EOC patients.

Treatment Rationale and Design for J-SONIC: A Randomized Study of Carboplatin Plus Nab-paclitaxel With or Without Nintedanib for Advanced Non–Small-cell Lung Cancer With Idiopathic Pulmonary Fibrosis

We describe the treatment rationale and procedure for a randomized study (J-SONIC; University Hospital Medical Information Network Clinical Trials Registry identification no., UMIN000026799) of carboplatin plus nanoparticle albumin-bound paclitaxel (nab-paclitaxel) with or without nintedanib for patients with advanced non–small cell lung cancer (NSCLC) and idiopathic pulmonary fibrosis (IPF). The study was designed to examine the efficacy and safety of nintedanib administered with carboplatin plus nab-paclitaxel versus carboplatin plus nab-paclitaxel alone in chemotherapy-naive patients with advanced NSCLC associated with IPF. Eligible patients (enrollment target, n = 170) will be randomized at a 1:1 ratio to receive 4 cycles of carboplatin (area under the curve, 6 on day 1) plus nab-paclitaxel (100 mg/m2 on days 1, 8, and 15) administered every 3 weeks either without (arm A) or with (arm B) nintedanib (150 mg twice daily), to be followed in arm B by single-agent administration of nintedanib (150 mg twice daily). The present trial is the first randomized controlled study for the treatment of NSCLC associated with IPF. The goal of the study is to demonstrate that nintedanib combined with carboplatin plus nab-paclitaxel prolongs the interval to acute exacerbation of IPF compared with carboplatin plus nab-paclitaxel alone.