First-line Treatment Of Stage Research Articles

Vinorelbine as First-Line Treatment in Stage IV Canine Primary Pulmonary Carcinoma.

Vinorelbine (VRL), a semi-synthetic vinca alkaloid commonly used in humans with advanced lung cancer, reaches high concentrations in the lung tissue, has proven antineoplastic activity and a low toxicity profile in dogs. Treatment-naïve, client-owned dogs with a cyto/histological diagnosis of advanced pulmonary carcinoma, selected from a laboratory database and previously subjected to imaging, were enrolled in the study. Vinorelbine (15 mg/m2) was administered weekly for 4 weeks and then fortnightly until progressive disease was documented. Staging work-up was repeated by means of diagnostic imaging after the fourth VRL (i.e., 28 days) and monthly thereafter; response to treatment was evaluated according to the RECIST. Toxicity was graded following the VCOGC group. Ten dogs met the inclusion criteria. Partial response was documented in eight dogs. Median time to progression was 88 days (range: 7-112) and median survival time for all dogs was 100 days (range 7-635). The most common side effect was neutropenia. The main limitations of the study were the absence of histological diagnosis in eight cases and the limited number of treated dogs. VRL is well tolerated with an adequate toxicity profile and may be useful in the management of advanced lung tumours if used as a first-line treatment strategy.

OA07.05 Gemcitabine Plus Platinum Chemotherapy Re-challenge in Metastatic Pulmonary Lymphoepithelioma-like Carcinoma

Pulmonary lymphoepithelioma-like carcinoma (LELC) is a rare subtype of non-small cell lung cancer. While first line treatment for stage IV disease with gemcitabine plus either cisplatin (GP) or carboplatin (GC) is more established with encouraging objective response rate, there is no consensual subsequent treatment strategy upon progression. In view of their potent efficacy in the first line setting, re-challenge gemcitabine-platinum is considered a reasonable option, but efficacy data is currently lacking.

CO-STAR: Surgical conversion feasibility trial of sintilimab (PD-1 inhibitor) combined with Nab-PTX, S-1 and apatinib for the first-line treatment of stage IV gastric cancer (GC).

e16041 Background: Chemotherapy and PD-1 inhibitor have shown significant clinical benefits in first-line treatment of GC, overall survival was still dismal. The surgical intervention with curative or life prolonging intention was evaluated as feasible for stage IV GC from clinical trials and retrospective cohorts. Our previous study of cytotoxic chemotherapy (S-1 & PTX) in combination with multi-targets anti-angiogenic TKIs illustrated increased response and R0 resection rate. Given the enhanced response from chemo, PD-1 and TKIs regimens, this trial was designed to assess the feasibility of surgical conversion from this combination in stage IV GC. Methods: This is a prospective, single-arm, single-center, phase II trial. Eligible criteria were treatment naïve, histopathologically confirmed stage IV (AJCC8th) and ECOG PS 0-1 GC adenocarcinoma. Pts were given with sintilimab (200mg, iv, d1) combined with Nab-PTX (w/o peritoneal spread: 260 mg/m2, iv, d1; w/ peritoneal spread: 180 mg/m2, iv, d1 and 80 mg/m2, ip, d1), S-1 (60mg, po, bid, d1-14), and apatinib (250mg, po, qd) every 3 wks. Tumor response was assessed every 2-4 cycles by radiologic imaging and MDT was employed to determine surgical feasibility. Safety run-in was employed in the first 3+3 pts by DLTs to determine the tolerability. The primary endpoint was ORR and R0 surgical conversion rate. Results: 42 pts were enrolled up to 2/2021. The median follow-up was 3.5m (range 0.7-11.3). The median age was 56 yrs (range 31-72), male was 47.6%, and PS 1 was 31.0%. The metastatic factors were characterized as No.16 lymph nodes 54.8% (23), liver 23.8% (10), peritoneum 40.5% (17), Krukenberg 2.4% (1), and extensive metastases (≥2 organs) 42.9% (18). No DLT occurred in initial 6 pts. Of 36 evaluable pts, ORR was 61.1% and DCR was 97.2%. Surgical conversion was currently identified in 18 pts with 94.4% (17) R0 resection, and the R0 surgical conversion rate was 47.2% (17/36). Median treatment cycle in converted pts was 4. 22.2% (4/18) pts achieved pathological complete response (TRG 0), and 27.8% (5/18) pts had major response (TRG 0-1). The most common AEs were grade 1-2, and 1 SAE of hemorrhage grade 4 occurred. No increase of anastomotic leakage, hemorrhage, and abdominal infection, and no surgery caused death and complication caused second operation occurred. The median postoperative length of stay was 9.5d (range 6-16). Conclusions: These preliminary results showed favorable tumor response and acceptable tolerability for potential surgical resection. Sintilimab, doublet chemotherapy, and apatinib might offer an opportunity of cure for stage IV gastric cancer. Trial ID: NCT04267549. Clinical trial information: NCT04267549. [Table: see text]

Systematic Review of Neoadjuvant Immunotherapy for Patients With Non–Small Cell Lung Cancer

There is a paucity of robust clinical evidence for the role of neoadjuvant immunotherapy in patients with resectable non-small cell lung cancer. The primary aim of the study was to identify the available data on the feasibility, safety and efficacy of neoadjuvant immunotherapy. A systematic review was conducted using electronic databases. Relevant studies were identified according to predefined selection criteria. Five relevant publications on 4 completed trials were identified. In most studies, >90% of patients were able to undergo surgery within the planned timeframe after neoadjuvant immunotherapy. There was a high incidence of open thoracotomy procedures, either planned or converted from a planned minimally invasive approach. Mortality ranged from 0 to 5%, but none of the reported deaths were considered directly treatment-related. Morbidities were reported according to adverse events related to neoadjuvant systemic therapy, and postoperative surgical complications. Survival outcomes were limited due to short follow-up periods. Major pathologic response ranged from 40.5 to 56.7%, whilst complete pathologic response of the primary tumor ranged from 15 to 33%. Radiological responses were reported according to RECIST criteria and fluorodeoxyglucose-avidity. This systematic review reported safe perioperative outcomes of patients who underwent resection following neoadjuvant immunotherapy. However, there was a relatively high incidence of open thoracotomy procedures, partly due to the technical challenges associated with increased fibrosis and inflammation of tissue, as well as the more advanced stages of disease in patients enrolled in the studies. Future studies should focus on identifying predictors of pathological response.

Microwave Ablation Versus Wedge Resection for Stage I Non-small Cell Lung Cancer Adjacent to the Pericardium: Propensity Score Analyses of Long-term Outcomes

ObjectiveThe present study has compared the long-term outcomes between performing wedge resection (WR) and microwave ablation (MWA) as first-line treatment of stage I non–small cell lung cancer (NSCLC) patients with tumors adjacent to the pericardium.Materials and MethodsBetween January 2014 and December 2018, a total of 223 consecutive patients with T1N0 NSCLC underwent first-line treatment by WR (n = 155) or image-guided lung MWA (n = 68). This study has compared the progression-free survival (PFS) and overall survival (OS) rates between the two treatments before and after propensity score matching. Subgroup analysis of these outcomes was conducted based on the distance from the pericardium.ResultsThe median follow-up time was 47 months. Propensity matching yielded 56 pairs of patients. In the two matched groups, the PFS rates in the WR group at 3 and 5 years were 66.0% and 56.0% and 54.0% and 36.0%, respectively, in the MWA group (P = 0.029). Meanwhile, the corresponding OS rates for the WR group at 3 and 5 years were 81.0% and 72.0% and 60.0% and 55.0% in the MWA group, respectively (P = 0.031). Subgroup analysis, done according to the treatment modality, indicated that local tumor recurrence and PFS for NSCLCs that were close but not contiguous to the pericardium were different from those contiguous to the pericardium (P = 0.018 and P = 0.025, respectively).ConclusionWR provided better long-term tumor control and OS compared to MWA for stage I NSCLC adjacent to the pericardium as a first-line treatment. MWA can be considered as an alternative option for high-risk and inoperable patients, particularly for tumors that were not contiguous to the pericardium.

The prognostic role of thyroid transcription factor-1 in lung adenocarcinoma.

In this study, we investigated the expression of thyroid transcription factor-1 (TTF-1) in lung adenocarcinoma patients' samples and analyzed the association of TTF-1 with clinicopathological parameters, prognosis, and treatment options in patients with lung adenocarcinoma. This retrospective study enrolled 200 patients who were histologically confirmed lung adenocarcinoma with Stage I-IV disease, between 2008 and 2015 years. The cytological archive of these hospitals' Pathology Department was searched. The available slides and the clinical information were reviewed and correlated. All analyses were conducted by SPSS version 15.0 statistical software. Sixty-five (32.5%) of the patients showed TTF-1 negativity and 135 (67.5%) of them showed TTF-1 positivity. The median survival for TTF-1 positive and negative patients was 19.6 and 12.2 months, respectively. We did not find any statistical significance in-between the parameters in terms of the survival data. In TTF-1-negative group, the survival time of epidermal growth factor receptor mutation positive (P = 0.049), cytokeratin 7 (CK7) positive (P = 0.009) patients and those who had received curative radiotherapy (P = 0.028) was significantly better as compared to TTF-1-positive group. We also analyzed the relation between TTF-1 and survival outcome or chemotherapy selection in Stage IV disease. We could not identify any correlation between TTF-1 and survival outcome or treatment selection. This study suggests that TTF-1 is not a favorable prognostic factor in lung adenocarcinoma patients. The prognostic role of CK7 and relationship between TFF-1 expression in lung adenocarcinoma and predictive role of TTF-1 expression for the selection of first-line treatment in Stage IV lung adenocarcinoma should be validated in prospective and randomized studies.

ENGOT-OV44/FIRST study: A randomized, double-blind, adaptive, phase III study of platinum-based therapy with dostarlimab (TSR-042) + niraparib versus standard-of-care (SOC) platinum-based therapy as first-line treatment of stage 3/4 non-mucinous epithelial ovarian cancer (OC).

TPS5600 Background: Despite surgery and SOC therapy (paclitaxel and carboplatin ± bevacizumab[bev]), 5-year survival rates remain low for patients (pts) with FIGO stage 3/4 OC. Niraparib (ZEJULA) is the first selective poly(ADP-ribose) polymerase inhibitor (PARPi) approved in the US and Europe for maintenance treatment in pts with recurrent OC regardless of BRCAmut status. Preclinical data suggest synergy with PARPi + anti-PD-1 blockade. Niraparib + pembrolizumab has shown clinical efficacy in pts with platinum-resistant or secondary refractory OC regardless of biomarker status. Dostarlimab is an anti–PD-1 humanized monoclonal with clinical activity as monotherapy in early phase trials. The primary objective of the currently enrolling FIRST trial is to compare PFS (per RECIST v1.1) in pts treated with SOC + dostarlimab + niraparib to SOC. Methods: Eligible pts (up to 912) are FIGO stage 3 (with residual disease, CC0 high risk, or planned neoadjuvant therapy) or stage 4, non-mucinous epithelial OC and ECOG score < 2. After 1 cycle of SOC, pts are stratified by concurrent bev use, BRCAmut/HRR status, and disease burden then randomized as 1:1:2 to 1 of 3 arms (Table). An innovative feature of ENGOT-OV44/FIRST (NCT03602859; EUDRACT 2018-000413-20) is the pre-planned adaptive study design to adapt the control arm to the evolving SOCs in OC, allowing pts in the control arm to receive up to date SOC. These adaptations will occur when practice-changing data are released. Following publication of SOLO1 results, BRCAmut pts will only be randomized to arm 2 or 3 to ensure they receive niraparib. Further adaptations may be incorporated as new data become available, leading to stop randomization in arm 1 or 2 of pts based on their biomarker status. Clinical trial information: NCT03602859. [Table: see text]

Staging of gastric cancer with the Clinical Stage Prediction score

BackgroundChemotherapy with or without surgery is the first-line treatment for stage III/IV gastric cancer, while surgery is the first-line treatment for stage I/II gastric cancer. Accordingly, it is important to distinguish between stage III/IV and stage I/II gastric cancer, but clinical staging is less accurate than pathological staging. This study was performed to develop a clinical score that could distinguish stage III/IV gastric cancer from stage I/II gastric cancer.MethodsWe reviewed 2722 patients who underwent gastrectomy at our hospital from January 1996 to December 2015. As pretreatment factors potentially related to tumor stage, we assessed age, sex, tumor markers, tumor diameter, tumor location, tumor histology, and macroscopic type. Factors showing significance on multivariate analysis were used to develop the Clinical Stage Prediction score (CSP score), and a cutoff value for the score was determined by receiver operating characteristics analysis.ResultsAccording to multivariate analysis, clinical factors associated with stage III/IV disease were elevation of the carcinoembryonic antigen level, tumor diameter ≥ 60 mm, circumferential gastric involvement, esophageal infiltration, mucinous adenocarcinoma, and macroscopic types 2–4.The CSP score was obtained by weighting these factors according to the non-standardized β-coefficient. Receiver operating characteristics analysis indicated that the optimum cutoff value of the CSP score was 17 points. Among 1042 patients with a CSP score ≥ 17 points, 820 patients (78.7%) had stage III/IV gastric cancer. Conversely, among 1680 patients with a CSP score < 17 points, 1547 patients (92.1%) had stage I/II gastric cancer. When discrimination of stage III/IV gastric cancer from stage I/II gastric cancer by the CSP score was assessed, the sensitivity was 78.7%, specificity was 92.1%, positive predictive value was 86.0%, and negative predictive value was 87.5%.ConclusionsThe CSP score can be helpful for differentiating stage III/IV gastric cancer from stage I/II gastric cancer based on pretreatment clinical factors.

A11474 Captophyte as an alternate regimen in controlling stage 1 essential hypertension

Objectives: According to NICE guidelines, first line treatment for stage 1 essential hypertension (EH) is either angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB). This clinical trial was designed to check the efficacy of a marine herbal compound vs Captopril in controlling first stage of EH (trial registration no: IRCT2015020110326N2) (patent registry number: IRIPO139350140003012176) Methods: A double blind phase 2 cross-over clinical trial was designed in patients with stage 1 EH. The hypertension was checked according to JNC-7 guidelines, biochemical tests were taken prior to initiation of anti-hypertensive medication. Inclusion criteria were: EH (Phase 1, no response to diet and exercise), no medications metabolized by CYP450. The patients were allocated randomly by random number generator. The patients either received Captopril 25 mg TID of Captophyte 2.050 g TID (compound with ACEI and renin inhibition (RI) mechanisms). After 2 weeks of treatment, patients had a washout period of 10 days with placebo and the medication was changed. During the treatment period patients were weekly monitored for blood pressure control. Data were analysed by descriptive statistics and paired t-test. Results: A total of 3600 patients were screened for EH and only 49 met the inclusion criteria (46 men and 3 women). Range of age was 25–55 yrs. SBP and DBP were 153 ± 4.53 mmHg, and 91.44 ± 2.44 mmHg, and after treatment the SBP and DBP were 130.16 ± 3.9 mmHg and 83 ± 2.41 mmHg respectively. Paired t-test was performed (p < 0.001) Conclusion: This compound which acts through RI and ACEI is equivocal to traditional ACEI in controlling HTN mainly because of chemical compounds which combat oxidative stress,(main culprit in pathogenesis of hypertension) and can be used as an alternate treatment for HTN

Gemcitabine-cisplatin (GC) + necitumumab (N) versus GC as first-line treatment for stage IV squamous cell lung cancer (SqCLC): An open-label randomized multicenter phase Ib-II trial in Japan.

9038Background: A randomized global phase III trial (SQUIRE) demonstrated statistically significant improvement in OS and PFS for GC+N versus GC in patients (pts) with advanced SqCLC. Methods: Phas...

Preoperative Pulmonary Function Tests (PFTs) and Outcomes from Resected Early Stage Non-small Cell Lung Cancer (NSCLC).

Preoperative pulmonary function tests (PFTs) predict operative morbidity and mortality after resection in lung cancer. However, the impact of preoperative PFTs on overall outcomes in surgically-resected stage I and II non-small cell lung cancer (NSCLC) has not been well studied. This is a retrospective study of 149 patients who underwent surgical resection as first-line treatment for stage I and II NSCLC at a single center between 2003 and 2014. PFTs [forced expiratory volume in 1 sec (FEV1), Diffusing Capacity (DLCO)], both absolute values and percent predicted values were categorized into quartiles. The Kaplan-Meier method and Cox regression analysis were used to determine whether PFTs predicted for overall survival (OS). Logistic regression was used to estimate the risk of postoperative complications and length of stay (LOS) greater than 10 days based on the results of PFTs. The median age of the cohort was 68 years. The cohort was predominantly males (98.6%), current or ex-smokers (98%), with stage I NSCLC (82.76%). The majority of patients underwent a lobectomy (n=121, 81.21%). The predominant tumor histology was adenocarcinoma (n=70, 47%) followed by squamous cell carcinoma (n=61, 41%). The median follow-up of surviving patients was 53.2 months. DLCO was found to be a significant predictor of OS (HR=0.93, 95% CI=0.87-0.99; p=0.03) on univariate analysis. Although PFTs did not predict for postoperative complications, worse PFTs were significant predictors of length of stay >10 days. Preoperative PFTs did not predict for survival from resected early-stage NSCLC, but did predict for prolonged hospital stay following surgery.

FDA expands approval of Adcetris for first-line treatment of Stage III or IV classical Hodgkin lymphoma in combination with chemotherapy

FDA expands approval of Adcetris for first-line treatment of Stage III or IV classical Hodgkin lymphoma in combination with chemotherapy

Research on the treatment of metastatic colon cancer patients treated by FOLFOXIRI: Efficacy and toxicity of first-line treatment in stage IV metastatic colorectal cancer patients

Background: In recent years, the new trend in treatment of colorectal cancer is the use of target drug. We conduct the study to evaluate efficacy of triplet combination chemotherapy of 5-fluorouracil/leucovorin, oxapilatin, and irinotecan (FOLFOXIRI) in the treatment of stage IV colorectal cancer patients. Method: Uncontrolled clinical trial carried on 39 stage IV colorectal cancer patients Results: The overall response rate of the treatment was 75%. Mean of progression free survival was 13.4 ± 9 months. The overall survival rate at 12th month and 24th month were 90% and 76%, respectively. The proportion of granulocytopenia was 48.9%, no grade 3 or 4. Side effect beyond hematology was most seen in hepatic toxicity with 52.5%, mainly at grade 1. Vomiting was 18.3%, all at grade 1. Other toxicity was very low at percentage. Conclusion: The triplet combination FOLFOXIRIN chemotherapy improves the outcome of patient with metal colorectal cancer in term of response rate, overall survival rate and progression free survival, and the level of toxicity was acceptable..

P3.02b-055 Impact of Pemetrexed Chemotherapy in Exon 19 or Exon 21 Mutated NSCLC: Topic: EGFR Clinical

EGFR mutation subtype is being increasingly recognized as factor impacting outcome of patients receiving oral TKI in non-small cell lung cancer. Data for the effect of this factor on the outcome in patients receiving chemotherapy is limited. We have the post hoc analysis of the study at our center to answer this question. We completed a study comparing pemetrexed with platinum vs. oral TKI in EGFR mutation positive patients in lung cancer. We analyzed the impact of EGFR mutation subtype, exon 19 and 21 on the PFS and OS of patients treated with pemetrexed (500mg/m2 on day 1) and carboplatin (AUC 5 on day 1) as first line therapy every 21 days. Patients underwent axial imaging for response assessment on D42, D84, D126 and subsequently every 2 months till progression. Responding or stable patients were treated until progression or unacceptable toxicity (post 6 cycles, patients were offered maintenance pemetrexed every 21 days). 143 patients received pemetrexed based therapy as first line treatment for stage III/IV NSCLC in the chemotherapy arm. 51 patients (36%) had exon 21 mutation while 92 patients (64%) had exon 19 mutation. Response rates in evaluable patients was 47.7% in exon 19 patients (41 patients, n=86) and 42.9 % in exon 21 patients (18 patients, n=42). There was a differential impact of EGFR mutation on PFS (p=0.028, HR=1.787, 95% CI 1.066- 2.998) in favor of exon 19 mutation. They also had a significant increase in median overall survival (24.5 months, 95% CI 21.3-27.7 months ) over the exon 21 mutated patients (18.1 months,95% Cl 13.5-22.6 months, p=0.002). In this study, EGFR exon 19 mutation had a differential impact on both PFS and OS in Indian patients of advanced-stage NSCLC treated with chemotherapy.

Maintenance based Bevacizumab versus complete stop or continuous therapy after induction therapy in first line treatment of stage IV colorectal cancer: A meta-analysis of randomized clinical trials.

In stage IV colorectal cancer, bevacizumab-based maintenance therapy, complete stop therapy and continuous therapy are considered all possible approaches after first line induction chemotherapy. However, there are no clear data about which approach is preferable. All randomized phase III trials comparing bevacizumab-based maintenance therapy (MB) with complete stop therapy (ST) or with continuous therapy (CT) were considered eligible and included into the analysis. Primary endpoint was the Time to failure strategies (TFS). Secondary endpoints were Overall Survival (OS) and Progression free survival (PFS). Meta-analysis was performed in line with the PRISMA statement. 1892 patients of five trials were included into the analysis. A significant improvement in TFS (HR 0.79; CI 95% 0.7-0.9 p=0.0005) and PFS (HR 0.56; CI 95% 0.44-0.71 p<0.00001) were observed in favour of MB versus ST. A trend, but not statistically significant, in favour of MB versus ST was also observed for OS (HR 0.88; CI 95% 0.77-1.01, p=0.08). Comparing maintenance therapy versus continuous therapy no statistically differences were observed in the outcomes evaluated (OS 12 months OR 1.1 p=0.62, OS 24 months OR 1 p=1, OS 36 months OR 0.54 p=0.3, TFS 12 months OR 0.76 p=0.65). Our meta-analysis suggests that use of MB approach increases TFS, PFS compared to ST. Although without observing any statistically advantage, it should be highlighted that MB versus ST showed a trend in favour of MB. We observed no difference between MB and CT. MB should be considered the standard regimen in patients with stage IV colorectal cancer after first line induction therapy.

Outcomes of stage I TTTS or liquor discordant twins: a single-centre review.

To investigate rates of progression, regression and stabilisation and outcomes for stage I twin-twin transfusion syndrome (TTTS) and significant liquor discordant (LD) monochorionic diamniotic (MCDA) twins referred to the New South Wales Fetal Therapy Centre between June 2007 and May 2013. Retrospective cohort study of 329 monochorionic referrals, of whom 47 had LD and 28 had stage I TTTS at presentation; 43 were stage I or higher at any time during surveillance. Clinical progression, rates of therapy, survival and associated complications were evaluated. Of stage I cases, 64% (18/28) remained stable or regressed, with 60% (6/10) of those progressing becoming at least stage II within 2 weeks. Of LD cases, 7/47 (15%) progressed to stage I TTTS, 8/47 (17%) to stage II or higher and 3/47 (6%) to selective intrauterine growth restriction (38% total). While a stable clinical picture was the most common outcome in stage I/LD presentations, progression to stage ≥ II TTTS occurred in 36 and 17% respectively, indicating that LD is not a benign finding. Rapid progression in the majority of progressive cases and modest overall survival rates support close surveillance of these pregnancies and investigation of laser therapy as a first-line treatment of stage I TTTS. © 2016 John Wiley & Sons, Ltd.

Pharmacologic Management of Pediatric Hypertension.

Hypertension in children is common, and the prevalence of primary hypertension is increasing with the obesity epidemic and changing dietary choices. Careful measurement of blood pressure is important to correctly diagnose hypertension, as many factors can lead to inaccurate blood pressure measurement. Hypertension is diagnosed based on comparison of age-, sex-, and height-based norms with the average systolic and diastolic blood pressures on three separate occasions. In the absence of hypertensive target organ damage (TOD), stage I hypertension is managed first by diet and exercise, with the addition of drug therapy if this fails. First-line treatment of stage I hypertension with TOD and stage II hypertension includes both lifestyle changes and medications. First-line agents include angiotensin-converting enzyme (ACE) inhibitors, thiazide diuretics, and calcium-channel blockers. Hypertensive emergency with end-organ effects requires immediate modest blood pressure reduction to alleviate symptoms. This is usually accomplished with IV medications. Long-term reduction in blood pressure to normal levels is accomplished gradually. Specific medication choice for outpatient hypertension management is determined by the underlying cause of hypertension and the comparative adverse effect profiles, along with practical considerations such as cost and frequency of administration. Antihypertensive medication is initiated at a starting dose and can be gradually increased to effect. If ineffective at the recommended maximum dose, an additional medication with a complementary mechanism of action can be added.

Maintenance bevacizumab versus stop and go therapy after induction therapy in first-line treatment of stage IV colorectal cancer: Pooled analysis of randomized clinical trials.

e14622 Background: In stage IV colorectal cancer, Bevacizumab maintenance therapy or stop and go therapy is considered the gold standard approach after first line induction chemotherapy. However, t...

The significance of EGFR pathway mutations for the efficacy of first line treatment with bevacizumab in metastatic colonrectal cancer.

699 Background: After analysis of minor RAS mutations (KRAS exon3, 4/NRAS) in FIRE-3 or PRIME study, so called all RAS mutation would be being regarded as a biomarker for anti-EGFR antibodies. BRAF and PIK3CA mutation would be a candidate of biomarkers for anti EGFR targeted therapies. However it remains unknown whether EGFR pathway mutations affect the efficacy of bevacizumab in Stage.‡W CRC. Methods: Of the 1,001 consecutive patients of CRC in our institute between Nov 2006 and Dec 2013, we examined RAS, PIK3CA and BRAF mutational status, 141 patients received systemic chemotherapy for the first line treatment of Stage.‡W. Among them, 96 patients were administered chemotherapy with bevacizumab. Overall survival (OS), Time to Treatment Failure (TTF) and Objective Response Rate (ORR) were evaluated by mutational status. Results: Baseline characteristics were as follows (n=141): median age, 63; male/female, 80/61; ECOG PS 0-1/2, 135/4; chemotherapy with bevacizumab/chemotherapy with anti-EGFR antibodies/cytotoxic agent alone, 96/22/23;KRAS (codon 12,13) wild-type (WT)/RAS wild-type(WT), 89/80; PIK3CA mutation (exon 9/exon 20)/BRAF mutation, 11(5/6)/13. Median OS and TTF were 32.1 and 8.0 months respectively. In chemotherapy with bevacizumab, ORRs were 46.3% (all cases), 55.3% (KRAS WT), 54.5% (RAS WT) and 60.6% (all WT) respectively. ORR was gradually improved by focusing therapeutic target on all wild population. However, there were no significant differences in TTF and OS among them. PIK3CA mutation had a trend toward shorter TTF of bevacizumab (p=0.056). This trend was observed in PIK3CA mutation on exon 20 but not observed exon 9. BRAF mutation had significantly associated with poor OS not only for bevacizumab cases but also all therapies. Conclusions: In our study, profiling of EGFR pathway mutations may not contribute to enrich patients with benefit from chemotherapy with bevacizumab.

Clinical investigation of efficacy of albumin bound paclitaxel plus platinum compounds as first-line chemotherapy for stage III/IV squamous non-small cell lung cancer.

To observe the efficacy and toxicity of nanoparticle albumin bound paclitaxel (nab-paclitaxel) plus platinum agent (cisplatin or carboplatin) as first line treatment for stage III/IV squamous non-small-cell lung cancer (NSCLC). Forty chemotherapy naive patients with stage III/IV squamous NSCLC received nab-paclitaxel 125 mg/m2 on day 1 and day 8, cisplatin 75 mg/m2 on day 1, carboplatin area under the concentration-time curve of 5 (AUC=5) on day 1. One cycle of treatment was 3 weeks, and at least two were completed in each case. Of the 40 patients who participated in the study, 25 achieved partial responses (PR), 12 reached a stage of stable disease (SD), and 3 suffered progressive disease (PD). The overall response rate (ORR) was 62.5% and the disease control rate (DCR) was 92.5%. Of the 20 patients without surgery or radiotherapy, 10 achieved PR, 7 reached a stage of SD, and 3 PD. The ORR was 50.0% and the DCR was 85.0%. The median progression-free survival time (PFS) of patients without surgery or radiotherapy was 5.0 months. Of the 20 patients receiving surgery or radiotherapy, 15 had PR and 5 p had SD, with an ORR of 75.0% and a DCR of 85.0%. Specifically, the DDP arm demonstrated a significantly higher ORR than the CBP arm (100%vs 54.5%, P<0.05). Common treatment related adverse events were myelosuppression, gastrointestinal response, baldness and neurotoxicity, most of which were grade 1 to 2. Nab-paclitaxel plus platinum agent (cisplatin or carboplatin) is effective as a first-line chemotherapy for stage III/IV squamous NSCLC, and its adverse effects are tolerable.