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Kaoru Kubota
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MA13 - Going Back to the Roots! (ID 139)
- Event: WCLC 2019
- Type: Mini Oral Session
- Track: Advanced NSCLC
- Presentations: 12
- Now Available
- Moderators:Maurice Perol, Kaoru Kubota
- Coordinates: 9/09/2019, 14:00 - 15:30, Vancouver (2003)
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MA13.01 - Associations Between Baseline Serum Biomarker Levels and Cachexia/Pre-Cachexia in Pretreated Non-Small Cell Lung Cancer (NSCLC) Patients (Now Available) (ID 2991)
14:00 - 15:30 | Presenting Author(s): Jeffrey Allen Borgia | Author(s): Gabriela C Lobato, Mary Jo Fidler, Jared D Fialkoff, Maneet Multani, Conner Wakefield, Sanjib Basu, Marta Batus, Philip Bonomi
- Abstract
- Presentation
Background
We previously reported associations of pretreatment serum biomarkers with clinical outcomes in a cohort of advanced NSCLC patients that progressed on front-line therapy. This study aims to elucidate mechanisms underlying cancer cachexia/ pre-cachexia by evaluating relationships between baseline serum biomarker values and sequential changes in body weight, body mass index (BMI), and neutrophil/lymphocyte ratio (NLR) in NSCLC patients.
Method
We used Luminex immunobead assays to survey 101 protein biomarkers in sera from advanced NSCLC (n=138) collected prior to their salvage regimen. Serial parameters associated with cancer cachexia included body weight, BMI, and NLR. Outcome variables (progression-free survival (PFS) and overall survival (OS)) were extracted with full IRB-approval. Biomarkers were evaluated as continuous variables with the cachexia surrogates using Pearson correlations, whereas associations of PFS and OS were accomplished with the Cox PH test.
Result
High baseline values of BMI and low baseline NLR were associated with both OS and PFS (each p<0.05), though weight failed to reach significance. PFS and OS were similarly associated with percent changes (relative to baseline) in weight (p<0.01), BMI (p<0.01), and NLR (p<0.001). Thirteen biomarkers were found to be associated (p<0.05) with baseline BMI values, including positive correlations with leptin, sol.VEGFR2, and c-peptide and inverse correlations with adiponectin, ferritin, ghrelin, IGFBP-1 and IL-8; fifteen biomarkers were associated with baseline NLR (all p<0.05), including positive correlations with visfatin, insulin, and serum amyloid A and inverse correlations with IGF-II. Fifteen biomarkers were found to be associated (p<0.05) in common with percent weight and BMI changes, including positive correlations with IGFBP-3 and inverse correlations with insulin, FGF-2, TNF-alpha, and resistin. Only prolactin and placental growth factor were found to be associated (p<0.05) with percent change in NLR.
Conclusion
A series of circulating protein biomarkers primarily connected with metabolic regulation and systemic inflammation/ acute phase response were found to be associated with cachexia/ pre-cachexia in NSCLC patients. Additional cohorts are currently being tested to verify these findings.
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MA13.02 - Incidence of Venous Thromboembolism at the Time of Lung Cancer Diagnosis: A Multicenter, Prospective Observational Trial (Rising-VTE/NEJ037) (Now Available) (ID 1195)
14:00 - 15:30 | Presenting Author(s): Kosuke Hamai | Author(s): Yukari Tsubata, Naoki Furuya, Tae Hata, Ryota Saito, Takeshi Masuda, Takamasa Hotta, Megumi Hamaguchi, Shoichi Kuyama, Ryoichi Honda, Kikuo Nakano, Masamoto Nakanishi, Kunihiko Funaishi, Masahiro Yamasaki, Nobuhisa Ishikawa, Kazunori Fujitaka, Tetsuya Kubota, Kunihiko Kobayashi, Takeshi Isobe
- Abstract
- Presentation
Background
Venous thromboembolism (VTE) is a most well-known kind of cancer associated thrombosis, and a common complication of malignancy. However, little is known about the incidence of VTE at the time of lung cancer diagnosis. This information is important for clinicians and patients to inform their decision-making about cancer treatment.
Method
The Rising-VTE/NEJ037 study was a multicenter, prospective, observational study with 40 participating Japanese institutions. It included 1,021 patients diagnosed with lung cancer unsuitable for radical resection or radiation between June 2016 and August 2018. The incidence of VTE and characteristics of patients diagnosed with VTE based on contrast-enhanced computed tomography or ultrasonography of the leg are described. Diagnosis of VTE was confirmed via central review by two radiologists.
Result
Baseline data was available for 1,013 patients. The median age was 71 years (range 30-94). Eighty-six percent of patients had non-small cell lung cancer and 13.5% had small cell lung cancer. Histological types included adenocarcinoma (N=645, 63.7%), squamous cell carcinoma (N=180, 17.8%), small-cell lung cancer (N=137, 13.5%) and others (N=42, 4.1%). There were 59 patients (5.8%) diagnosed with VTE, of whom 53.9% had deep vein thrombosis (DVT), 28.7% had pulmonary embolism (PE) and 24.6% had both DVT and PE. Most patients with VTE had adenocarcinomas (89.1%).
Conclusion
The incidence of VTE in this study seems to be higher than in the clinical setting, suggesting that screening may be desirable. Adenocarcinoma of the lung seems to be a risk factor for VTE that we should consider more carefully. The primary endpoint of this trial is the rate of symptomatic or asymptomatic recurrence or newly diagnosed VTE during 2 years after registration. Follow-up is ongoing, with a report of final findings planned for 2021. Clinical trial information: UMIN000020194. Funding: Daiichi Sankyo Company.
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MA13.03 - Retrospective Study of Intrathecal Therapy for Non-Small Cell Lung Cancer (NSCLC) Patients with Leptomeningeal Carcinomatosis (Now Available) (ID 2086)
14:00 - 15:30 | Presenting Author(s): Noelia Vilariño | Author(s): Juan Antonio Marín, Marta Simó, Roser Velasco, Montserrat Alemany, Maria Jove, Jose Carlos Ruffinelli, Isabel Brao, Monica Arellano, Ramon Palmero Sánchez, Jordi Bruna, Ernest Nadal
- Abstract
- Presentation
Background
Leptomeningeal carcinomatosis (LMC) is a devastating cancer-related neurological complication with poor prognosis. In EGFR-mutant (mut) NSCLC patients (pts), osimertinib achieves high penetration into cerebral-spinal fluid (CSF) and promising efficacy. However, for EGFR-mut T790M-negative pts treated with prior 1st- and 2nd-generation tyrosine kinase inhibitors (TKI) and for driver negative NSCLC pts, a combination of intrathecal therapy (IT) and systemic therapy (ST) seems to be an appropriate approach. Our purpose is to explore the clinical outcome of IT combined with ST among NSCLC with LMC depending on EGFR status.
Method
NSCLC pts with LMC treated with IT in our institution between 2010 and 2018 were retrospectively studied. After LMC diagnosis, intrathecal methotrexate (scheduled: 12mg twice weekly for 4 weeks, then 12mg weekly for 4 weeks) was given in combination with ST. A Kaplan-Meier survival analysis was performed for overall survival (OS) and progression free survival (PFS).
Result
A total of 39 pts were included. Patient’s clinical characteristics are summarized in table 1. EGFR status was 17 mut (del19: 11pts); 11 wild-type (wt) and 11 unknown (unk). LMC and NSCLC diagnosis were more likely to be synchronous in EGFR wt compared with EGFR mut. The median follow-up from LCM diagnosis was 10.2 months. At the time of this analysis, only 6 pts were alive. Thirty-two pts received ST in combination with IT, 18 (46%) pts chemotherapy (6wt/ 3mut/ 9unk), while 14 (36%) pts an EGFR TKI (1wt/ 13mut). Clinical response (improvement of neurological symptoms and/or KPS) was seen in 11 (65%) EGFR mut pts vs 2 (18%) wt pts (p=0.033). Median OS and PFS for the whole cohort were 23 weeks (95%CI, 8.1 to 37.9) and 10 weeks (95%CI, 7.1 to 12.8) respectively. Median OS was higher for EGFR mut pts compared to wt pts, 38 weeks (95%IC 13.6-62.4) and 19 weeks (95%IC, 4.06-33.9) respectively, however this difference was not statistically significant (p=0.36) probably due to lack of statistical power.
Conclusion
Methotrexate-based IT given concurrently with systemic TKI may confer a higher clinical benefit and a trend toward OS benefit in NSCLC patients with LCM and EGFR activating mutations.
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MA13.04 - Discussant - MA13.01, MA13.02, MA13.03 (Now Available) (ID 3776)
14:00 - 15:30 | Presenting Author(s): Ramaswamy Govindan
- Abstract
- Presentation
Abstract not provided
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MA13.05 - Nab-Paclitaxel Maintenance in Squamous Non-Small Cell Lung Cancer (NSCLC): Updated Results of the Phase III ABOUND.sqm Study (Now Available) (ID 294)
14:00 - 15:30 | Presenting Author(s): David R Spigel | Author(s): Robert M Jotte, Santiago Ponce Aix, Laurent Gressot, Daniel Morgensztern, Michael McCleod, Mark A Socinski, Davey Daniel, Oscar Juan, Kathryn F Mileham, HOWARD WEST, Ray Page, Niels Reinmuth, Jeanna Knoble, Olivia Yu Tian, Rafia Bhore, Marianne Wolfsteiner, Teng Jin Ong, Cesare Gridelli, Michael Thomas
- Abstract
- Presentation
Background
Background: nab-Paclitaxel maintenance therapy after nab-paclitaxel/carboplatin induction in patients with advanced squamous NSCLC was evaluated in the phase III, randomized, controlled, open-label, multicenter ABOUND.sqm trial. At the 12-month follow-up, there was no statistically significant difference in progression-free survival (PFS) between patients randomized to maintenance nab-paclitaxel + best supportive care (BSC) vs BSC alone. However, a trend of an overall survival (OS) advantage was observed with nab-paclitaxel + BSC vs BSC alone. Here we report the 18-month follow-up of OS.
Method
Methods: Patients (aged ≥ 18 years) with histologically or cytologically confirmed stage IIIB/IV squamous NSCLC and no prior chemotherapy were eligible. Patients received four 21-day cycles of nab-paclitaxel 100 mg/m2 (days 1, 8, and 15) plus carboplatin AUC 6 (day 1) as induction. Patients with radiologically assessed complete or partial response or stable disease without clinical progression after 4 cycles were randomized 2:1 to maintenance nab-paclitaxel 100 mg/m2 (days 1 and 8 of each 21-day cycle) plus BSC or BSC alone until disease progression. The primary efficacy analysis was performed on the ITT population. PFS from randomization into the maintenance part of the study was the primary endpoint. Secondary endpoints included safety, OS (from randomization), and response.
Result
Results: 420 patients received induction therapy; 202 were randomized to maintenance nab-paclitaxel + BSC (n = 136) or BSC alone (n = 66). The median PFS in patients in the nab-paclitaxel + BSC arm vs those in the BSC-alone arm was 3.1 vs 2.6 months (HR, 0.85; P = 0.349), respectively; the median OS was 17.8 vs 12.2 months (HR, 0.71; P = 0.058), respectively. The overall response rate was 69.1% vs 57.6% (RRR, 1.20; P = 0.087). Following the maintenance part, 73.5% (nab-paclitaxel + BSC) and 68.2% (BSC alone) of patients received subsequent anti-cancer treatment. Over the entire study, the most frequent grade 3/4 TEAEs were neutropenia (53.1% vs 50.0%) and anemia (33.1% vs 32.3%); only peripheral neuropathy occurred in ≥ 5% of patients during maintenance (13.1% in the nab-paclitaxel + BSC arm).
Conclusion
Conclusion: Although PFS and OS differences were not statistically significant in the ITT population, the 18-month follow-up of OS demonstrated the feasibility of nab-paclitaxel maintenance therapy for patients with anced squamous NSCLC.
ClinicalTrials.gov identifier: NCT02027428
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MA13.06 - Ph3 Study of Maintenance Therapy with S-1 vs BSC After Induction Therapy with Carboplatin + S-1 for Advanced Squamous Cell Lung Cancer (WJOG7512L) (Now Available) (ID 563)
14:00 - 15:30 | Presenting Author(s): Kaoru Tanaka | Author(s): Satoshi Morita, Masahiko Ando, Takuma Yokoyama, Atsushi Nakamura, Hiroshige Yoshioka, Takashi Ishiguro, Satoru Miura, Ryo Toyozawa, Tetsuya Oguri, Haruko Daga, Ryo Ko, Akihiro Bessho, Motoko Tachihara, Yasuo Iwamoto, Katsuya Hirano, Yoichi Nakanishi, Kazuhiko Nakagawa, Nobuyuki Yamamoto, Isamu Okamoto
- Abstract
- Presentation
Background
Our previous phase 3 study established carboplatin plus the oral fluorinated pyrimidine formulation S-1 as a standard option for first-line treatment of advanced non–small cell lung cancer (NSCLC) (J Clin Oncol 2010; 28:5240). The importance of maintenance therapy for patients with advanced squamous NSCLC has been unknown, however.
Method
WJOG7512L was designed as a randomized phase 3 study to evaluate whether maintenance therapy with S-1 improves clinical outcome after induction therapy with carboplatin plus S-1 in such patients. Before randomization, patients received carboplatin (AUC of 5 on day 1 every 3 weeks) plus S-1 (40 mg/m2 twice per day on days 1 to 14 every 3 weeks) as induction therapy. Those who did not progress after four cycles of induction therapy were randomized to receive either S-1 plus best supportive care (BSC) or BSC alone. The primary objective was to confirm the superiority of S-1 plus BSC with regard to progression-free survival.
Result
Of the 365 patients enrolled, 347 participated in the induction phase and 131 of these individuals were randomized to receive S-1 plus BSC (n = 67) or BSC alone (n = 64). Baseline demographics and clinical characteristics of the subjects, including the response to induction therapy, were well balanced. Patients receiving S-1 plus BSC showed a significantly reduced risk of disease progression compared with those receiving BSC alone (hazard ratio [HR], 0.548; 95% confidence interval [CI], 0.374–0.802; P = 0.0019). Median overall survival from randomization did not differ significantly between the two arms: 17.8 months for BSC alone and 16.7 months for S-1 plus BSC (HR, 0.890; 95% CI, 0.583–1.357). Time to deterioration in quality of life also showed no significant difference (P = 0.8754 for FACT-TOI, P = 0.9016 for FACT-LCS). The incidence of adverse events during maintenance therapy was low, with neutropenia, anemia, and thrombocytopenia of grade 3 or 4 each occurring in ~1% to 4% of patients.
Conclusion
Maintenance with S-1 plus BSC is an effective and well-tolerated treatment option for patients with advanced squamous NSCLC.
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MA13.07 - Phase I/II Study of Carboplatin Plus Weekly Nab-Paclitaxel in Aged ≥75 Patients with Squamous-Cell Lung Cancer: TORG1322 (Now Available) (ID 1369)
14:00 - 15:30 | Presenting Author(s): Yoshitaka Zenke | Author(s): Seiji Niho, Shigeki Umemura, Masashi Ishihara, Ryosuke Ochiai, Naoyuki Nogami, Yukio Hosomi, Tsuneo Shimokawa, Takaaki Tokito, Yasushi Goto, Yosuke Miura, Haruhiro Saito, Naoya Hida, Satoshi Ikeda, Hiroshi Tanaka, Naoki Furuya, Toshihiro Misumi, Yuichiro Ohe, Hiroaki Okamoto
- Abstract
- Presentation
Background
Combination chemotherapy of carboplatin (CBDCA) plus weekly nab-paclitaxel (nab-PTX) showed a favorable efficacy for elderly (70 year or older) patients with squamous non-small cell lung cancer (Sq-NSCLC) in a subgroup analysis of the CA031 study. We conducted a phase I/II study of CBDCA plus nab-PTX in chemo-naïve elderly patients with advanced Sq-NSCLC.
Method
Patients aged ≥75 years with untreated, measurable lesion, advanced Sq-NSCLC, performance status (PS) 0-1, and adequate organ function were eligible. In a phase I study, doses of carboplatin at an area under the curve (AUC) of 5 or 6 mg/mL min on day 1 (levels 1 and 2, respectively) were administered along with weekly nab-PTX (100 mg/m2) on days 1, 8, and 15 every 4 weeks up to 6 cycles using a modified 3 + 3 design. The primary endpoint for the phase II study was the 6-month progression-free survival (6m PFS) rate and hypothesis required 36 patients to be enrolled with expecting and threshold values for the primary endpoints of 40% and 25% (one-sided alpha = 0.05; beta = 0.2).
Result
A total of 46 patients were enrolled in this study. The median age was 78 (range 75-85 years); male (n = 41); PS 0/1, (n = 15/31). Ten patients were enrolled in the phase I part. At dose level 1, 2/7 patients showed dose-limiting toxicities (DLTs) of grade 3 diarrhea and febrile neutropenia, and at dose level 2, 1/3 patient showed DLT of grade 3 anorexia. The recommended dose was determined to be level 2. Additional 36 patients were enrolled, and a total of 39 patients were evaluated in the phase II study. The median number of cycles was 4 (range 1-6), and the median follow-up time was 17.5 months (range 5.6-28.9). The 6m PFS rate was 59% (90% CI, 44.8-71.4), and the primary endpoint was met. The median overall survival time was 23.5 months (95% CI, 11.6-35.4), and the median PFS was 6.8 months (95% CI, 5.4-9.1). The response rate was 54% and disease control rate was 92%. Nineteen patients (49%) received post-study treatment and 14 out of 19 patients (74%) received immunotherapy. Common toxicities of grade 3 or 4 were neutropenia (61.5%), anemia (46.2%), thrombocytopenia (17.9%), and febrile neutropenia (15.4%). There was no treatment-related death.
Conclusion
Combination chemotherapy of CBDCA plus weekly nab-PTX had a promising efficacy and acceptable toxicities in elderly (aged ≥75) patients with advanced Sq-NSCLC. Clinical trial information: UMIN000011216.
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MA13.08 - Discussant - MA13.05, MA13.06, MA13.07 (Now Available) (ID 3775)
14:00 - 15:30 | Presenting Author(s): Karen L Reckamp
- Abstract
- Presentation
Abstract not provided
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MA13.09 - Cisplatin Sustains Lung Cancer Metastasis Through the Systemic Activation of SDF-1/CXCR4 Axis (Now Available) (ID 2821)
14:00 - 15:30 | Presenting Author(s): Giulia Bertolini | Author(s): Valeria Cancila, Claudio Tripodo, Gabriella Sozzi, Giuseppe Lo Russo, Orazio Fortunato, Massimo Milione, Giovanni Centonze, Monica Tortoreto, Stefania Scala, Luca Roz
- Abstract
- Presentation
Background
Standard chemotherapy regimens have limited long-term efficacy in lung cancer patients due to chemoresistance and inefficacy in controlling metastatic disease. In pre-clinical models we have shown that cisplatin treatment enriches for the chemoresistant fraction of CD133+CXCR4+ lung cancer metastasis initiating cells (MICs), increasing distant metastasis development that can be prevented by CXCR4 blockade. Therefore, we hypothesize that the SDF-1/CXCR4 axis, implied in MICs maintenance/migration and in immune and stromal cells trafficking, could play a critical role in cisplatin-induced pro-metastatic effects.
Method
To study the effects of cisplatin in promoting a pre-metastatic niche, naïve SCID mice were treated with cisplatin plus/minus peptide R (5mg/kg), a novel inhibitor of CXCR4 and after 72h injected intravenously with metastatic H460 cell line. To assess the effect of the combination treatment in pre-clinical model, H460 subcutaneous xenografts were treated with cisplatin alone or with peptide R for three weeks. Content of MICs in xenografts, number and phenotype of lung metastasis and immune cells modulationt were evaluated by FACS and IHC
Result
We showed that cisplatin treatment of naïf SCID mice resulted in a rapid BM expansion of the subset of CCR2+CXCR4+Ly6Chigh inflammatory monocytes (IM), concomitantly with their recruitment to murine lungs guided by increased level of SFD-1 released by PDGFRβ+ stromal cells in response to cisplatin. Peptide R partially prevented these effects.
Tail-vein injection of H460 human lung cancer cells 72h after cisplatin administration resulted in augmented number of lung metastases (p=0.003), that showed a 3.5-fold enrichment in CD133+CXCR4+ MICs (p=0.005) and increase of IM and derived macrophages. Pre-treatment with peptide R abolished these effects. We verified that the abundance of CXCR4+CCR2+IM together with increased endothelial permeability caused by cisplatin may favor tumor cells extravasations and expansion of MICs through SDF-1/CXCR4 axis activation which determined metastasis overgrowth.
SDF-1 was also increased in cisplatin-treated subcutaneous H460 xenografts that expanded the subset of chemoresistant CD133+CXCR4+ MICs and recruited CXCR4+tumor associated macrophages which may allow MICs to escape primary tumor. At the metastatic site cisplatin treatment of H460 xenografts caused an increase in stromal SDF-1 and recruitment of both CXCR4+ inflammatory monocytes/macrophages (1.6-fold change p=0.01) and MICs subset (1.8-fold change p=0,04), overall resulting in a boost in micrometastases. CXCR4 inhibition prevented the co-recruitment and cross-talk of MICs and IM at distant site, counteracting the pro-metastatic effects of cisplatin.
Matched case series of stage III chemo-naive NSCLC patients and cisplatin-based neo-adjuvant treated patients demonstrated a significant increased in SDF-1 after chemotherapy (p=0,0001). An high expression of tumoral SDF-1 ( Score: staining intensity x % positive tumor cells >6) induced by cisplatin neo-adjuvant treatment was associated with a shorter DFS (p=0,0056) and poor OS (p=0,029).
Conclusion
Conclusions: Our data reveal a paradoxical pro-metastatic effect of cisplatin that fosters MIC-IM recruitment and cross-talk via SDF-1/CXCR4 axis activation. A new combination strategy based on CXCR4 inhibition may disrupt these interactions, providing more effective and long-lasting results for lung cancer treatment
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MA13.10 - A Phase II Study of Carboplatin and Nab-Paclitaxel for Advanced Non-Small Cell Lung Cancer with Interstitial Lung Disease (HOT1302) (Now Available) (ID 990)
14:00 - 15:30 | Presenting Author(s): Hiroshi Yokouchi | Author(s): Hajime Asahina, Satoshi Oizumi, Kei Takamura, Toshiyuki Harada, Masao Harada, Kenya Kanazawa, Yuka Fujita, Tetsuya Kojima, Fumiko Sugaya, Hisashi Tanaka, Ryoichi Honda, Takahiro Ogi, Eiki Kikuchi, Tomoo Ikari, Hirotoshi Dosaka-Akita, Hiroshi Isobe, Masaharu Nishimura
- Abstract
- Presentation
Background
Because of the high risk of exacerbation of pre-existing interstitial lung disease (ILD), patients with concomitant advanced non-small cell lung cancer (NSCLC) and ILD have been excluded from most clinical trials of chemotherapy, despite the high prevalence (around 10%) of all NSCLC cases. This study prospectively evaluated the efficacy and safety of albumin-bound paclitaxel (nab-paclitaxel) in combination with carboplatin in advanced NSCLC patients with pre-existing ILD.
Method
Enrolled patients had treatment-naïve, advanced NSCLC with pre-existing ILD. Patients received 100 mg/m2nab-paclitaxel weekly and carboplatin at area under the concentration-time curve (AUC) 6 once every 3 weeks for 4-6 cycles. The primary endpoint was overall response rate (ORR); secondary endpoints included toxicity, progression-free survival (PFS) and overall survival (OS). The interactions between histology [Squamous (Sq) vs. Non-Squamous (Non-Sq)] and treatment outcomes were also investegated.
Result
Thirty-six patients were enrolled between April 2014 and September 2017. Sixteen patients (44.4%) had an adenocarcinoma, followed by 15 (41.7%) squamous cell carcinoma, and 5 (13.9%) non-small cell carcinoma. The median number of cycles administered were 4 (range: 1-6). The ORR, the primary endpoint, was 55.6% (95% confidence interval [CI]: 39.6-70.5%). The median PFS and OS were 5.3 months (95% CI: 3.9-8.2 months) and 15.4 months (95% CI: 9.4-18.7 months), respectively. There was no significant difference between two groups, however, numerically better treatment outcomes were observed in the Sq group: the ORR was 66.7% (95% CI: 41.7–84.8%) in the Sq group compared with 47.6 % (95% CI: 28.3–67.6%) in the Non-Sq group (P =0.254); median PFS was 8.2 months (95% CI: 4.0–10.2 months) in the Sq group vs. 4.1 months (95% CI: 3.3-5.4 months) in the Non-Sq group (HR, 0.60 [95% CI, 0.30–1.20]; p=0.15); median OS was 16.8 months (95% CI: 9.8 months–not reached) in the Sq group vs. 11.9 months (95% CI: 7.3-17.4 months) in the Non-Sq group (HR, 0.56 [95% CI, 0.24–1.28]; p=0.17). Two patients (5.6%) experienced grade ≥2 pneumonitis and one patient (2.8%) died.
Conclusion
This is the first prospective phase 2 study of weekly nab-paclitaxel in combination with carboplatin in advanced NSCLC patients with pre-existing ILD. This treatment showed favorable efficacy and was well tolerated.
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MA13.11 - A Randomized Phase III Study of Cisplatin-Polymeric Micelle Paclitaxel vs Cisplatin-Solvent-Based Paclitaxel in 1st Line Advanced NSCLC (Now Available) (ID 696)
14:00 - 15:30 | Presenting Author(s): Yi-Long Wu | Author(s): Baohui Han, Meiqi Shi, Haiyan Tu, Aiqin Gu, Cheng Huang, Huijuan Wang, Zhuang Yu, Xiuwen Wang, Lejie Cao, Yongqian Shu, Huaqing Wang, Runxiang Yang, Xingya Li, Jianhua Chang, Yanping Hu, Peng Shen, Yi Hu, Zhongliang Guo, Min Tao, Yiping Zhang, Xunyan Liu, Qian Sun, Xin Zhang, Zuguang Jiang, Junhui Zhao, Feng Chen, Jing Sun, Duan Li, Jinsong Zhou
- Abstract
- Presentation
Background
Cisplatin-sb-Pac is the one of current standard of chemotherapy in aNSCLC, It produced 15% to 32% objective response rate (ORR) and 7.9 to 10.6 months of median overall survival (OS). Alternative nab-paclitaxel to sb-Pac only increased ORR but not improved progression-free survival (PFS) and OS. Thus the unmet medical need for new chemo regimen remains.
Method
From May 2015 to Jan 2018 448 untreated patients (pts) with stage IIIB to IV NSCLC from 24 sites were randomly assigned 2:1 to receive 230 mg/m2 pm-Pac and cisplatin 70 mg/m2 on day 1 of a 3-week cycle, and then dose escalation of pm-Pac to 300 mg/m2 from the second cycle if no prespecified toxic effects observed or 175 mg/m2 sb-Pac plus cisplatin 70 mg/m2 once every 3 weeks. Pts were stratified by stage and histology. The primary end point was ORR by Independent review committee (IRC) and Investigator (INV) in the intent-to-treat population. The second endpoints included PFS, OS and safety. Data cutoff was Jan 26, 2019.
Result
300 pts were assigned to pm-Pac and 148 to sb-Pac. Baseline characteristic were balance in both arms. Nonsquamous carcinoma (non-squ) and stage IV were 57.3% and 81.0% in pm-Pac and 58.1% and 81.8% in sb-Pac respectively. 73.2% pts in pm-Pac arm escalated their dose to 300mg/m2, 0.7% down to 184mg/m2. ORR and PFS in pm-Pac were significant better than that in sb-Pac (table 1). OS was immature. For histology subgroup the ORR was 58.6% v 37.1% (P=0.0054) in squamous carcinoma (Squ) and 44.2% v 18.6% (P<0.0001) in non-squ. Grade ≥3 AEs was 80.0% for pm-Pac and 79.7% for sb-Pac. No new safety issues were identified.
Conclusion
The phase 3 trial met its primary endpoint. pm-Pac significantly improved ORR and PFS than sb-Pac, and pm-Pac regimen should be a new standard chemo for aNSCLC. (NCT 02667743).
Tab. Efficacies comparison between pm-Pac and sb-Pac
pm-Pac
sb-Pac
P value
ORR % (95% CI)
IRC
INV
50.3 (44.5-56.1)
52.0 (46.2-57.8)
26.4 (19.5-34.2)
28.4 (21.3-36.4)
<0.0001
<0.0001
PFS (months)
6.4 (6.2-6.9)
5.3 (4.6-6.0)
HR 0.66 (0.52-0.84), P=0.0006
OS at 12 months
67.3%
61.8%
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MA13.12 - Discussant - MA13.09, MA13.10, MA13.11 (Now Available) (ID 3774)
14:00 - 15:30 | Presenting Author(s): Lyudmila Bazhenova
- Abstract
- Presentation
Abstract not provided
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Author of
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P1.01 - Advanced NSCLC (ID 158)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.01-112 - Phase 3, Randomized, Double-Blind Trial of First-Line Pembrolizumab With or Without Lenvatinib in Metastatic NSCLC: LEAP-007 (ID 1406)
09:45 - 18:00 | Author(s): Kaoru Kubota
- Abstract
Background
The anti–PD-1 antibody pembrolizumab, as monotherapy or in combination with chemotherapy, is the standard of care for most patients with untreated metastatic non–small-cell lung cancer (NSCLC) with no EGFR/ALK aberrations. Lenvatinib is an anti-angiogenic multireceptor tyrosine kinase inhibitor that enhanced the antitumor activity of PD-1 inhibitors in vitro and showed clinical activity in combination with pembrolizumab in patients with metastatic NSCLC in a recent open-label, phase 1b/2 study (NCT02501096). LEAP-007 (NCT03829332) further evaluates the safety and efficacy of pembrolizumab plus lenvatinib in patients with metastatic NSCLC.
Method
This randomized, double-blind, phase 3 trial enrolls previously untreated adult patients with stage IV NSCLC and PD-L1 TPS ≥1% without sensitizing genetic aberrations. Patients are randomized 1:1 to pembrolizumab 200 mg Q3W plus lenvatinib 20 mg daily or pembrolizumab plus matching placebo, stratified by geographic region (East Asia vs other), ECOG PS (0 vs 1), and TPS (1%–49% vs ≥50%). Treatment continues until verified disease progression (PD), unacceptable AE, illness, withdrawal of consent, noncompliance, or administrative reason. Radiographic imaging occurs Q9W from randomization through 54 weeks, then every 12 weeks until confirmed PD or start of a new anticancer regimen, and is assessed by blinded independent central review (BICR) using RECIST v1.1. Primary outcomes are PFS (RECIST v1.1 by BICR) and OS. Secondary outcomes include ORR (RECIST v1.1 by BICR), safety (AEs graded according to NCI CTCAE v4.0), and health-related quality of life. PFS and OS will be analyzed using the Kaplan-Meier method and stratified log-rank test; hazard ratios will be estimated using a stratified Cox regression model. ORR will be analyzed using the stratified Miettinen and Nurminen method, and differences will be estimated using the stratified Miettinen and Nurminen method with strata weighting by sample size. Target enrollment is 620 patients from 165 sites. As of April 5, 2019, 13 patients have been screened.
Result
Not applicable
Conclusion
Not applicable
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P2.14 - Targeted Therapy (ID 183)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.14-41 - Risk Factors for Brain Metastasis in Patients with EGFR Mutant Non-Small Cell Lung Cancer (ID 1036)
10:15 - 18:15 | Author(s): Kaoru Kubota
- Abstract
Background
Brain metastasis is associated with a poor prognosis in patients with EGFR mutant non-small cell lung cancer (NSCLC). EGFR tyrosine kinase inhibitors (TKIs) may be an effective treatment, but their influence on brain metastasis development is unclear. We aimed to identify risk factors for brain metastasis in patients with EGFR-mutant NSCLC.
Method
This retrospective study included 166 consecutive advanced NSCLC patients with EGFR major mutations (Ex 21 L858R or Ex 19 del) who received EGFR–TKI monotherapy at the Nippon Medical School Hospital and Nippon Medical School Tamanagayama Hospital from November 2010 to June 2018. Patients who had brain metastases before EGFR–TKI monotherapy were excluded. We evaluated the cumulative actuarial incidence of brain metastases by Gray’s test, univariate and multivariate analyses.
Result
The median age was 72 years (range, 26-95 years), the majority of patients were female (n=103), and most patients had adenocarcinoma (n=153). Patients carried either an EGFR L858R (n=88) or 19del (n=78) mutation, and had been treated with gefitinib (n=97), erlotinib (n=22) or afatinib (n=47). The time to brain metastasis did not significantly differ between the three EGFR-TKI groups. The time to brain metastasis was significantly shorter in patients <75 years than >75 years (29.0 months versus not reached; HR 4.70; 95% CI 1.72-12.87). Univariate and multivariate analyses showed that age <75 years and non-adenocarcinoma histology were significant predictors of brain metastasis. In patients <75 years, the time to brain metastasis in patients who underwent EGFR-TKI dose reduction or intermittent treatment was significantly shorter than patients with constant EGFR-TKI treatment (24.9 versus 39.9 months; HR 2.40; 95% CI 1.10-5.22).
Conclusion
Age <75 years is a risk factor for brain metastasis in patients with EGFR mutant NSCLC. We do not recommend EGFR–TKI dose reduction or intermittent administration in these patients.
