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G. Blumenschein
Moderator of
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ORAL 01 - Chemotherapy Developments for Lung Cancer (ID 88)
- Event: WCLC 2015
- Type: Oral Session
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 7
- Moderators:G. Blumenschein, S. Lee
- Coordinates: 9/07/2015, 10:45 - 12:15, 401-404
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ORAL01.01 - Randomized Phase III Study of Nedaplatin plus Docetaxel versus Cisplatin plus Docetaxel for Advanced Squamous Cell Lung Cancer (WJOG5208L) (ID 621)
10:45 - 12:15 | Author(s): T. Seto, T. Shukuya, T. Yamanaka, T. Hirashima, T. Kato, Y. Horio, S. Atagi, T. Inoue, Y. Ohsaki, T. Maeda, K. Nishi, T. Sawa, M. Okada, D. Fujimoto, T. Harada, K. Nakagawa, Y. Nakanishi, N. Yamamoto
- Abstract
- Presentation
Background:
Nedaplatin (N) is a second-generation platinum compound with lower nausea/vomiting and nephrotoxicity than cisplatin (C). Nedaplatin plus docetaxel (ND) showed a promising efficacy with acceptable toxicity for advanced squamous cell lung cancer (SqLC) in the previous phase II study.
Methods:
Eligible patients (pts) were those with pathologically proven SqLC with stage IIIB/IV or postoperative recurrence, aged 20-74 years and ECOG PS 0-1. Pts were randomized 1:1 to ND (N 100 mg/m[2] and docetaxel (D) 60mg/m[2] iv, q3w, up to 6 cycles) or C plus D (CD) (C 80 mg/m[2] and D 60mg/m[2] iv, q3w, up to 6 cycles) according to stage, gender and institution. The primary endpoint was overall survival (OS), and secondary endpoints included progression-free survival (PFS), response rate (RR) and adverse events (AEs). Target sample size of 350 provided 90% statistical power to detect a hazard ratio of 0.71 with one-sided type I error of 0.05.
Results:
Between July 2009 and July 2012, 355 pts were randomized. Of 349 for efficacy analysis (ND 177; CD 172), baseline characteristics were well-balanced between two arms. ND had a significantly longer OS (p=0.037, one-sided stratified log-rank test). The OS HR was 0.81 (90%CI, 0.67-0.98) with a median OS of 13.6 months [m] for ND and 11.4 for CD. ND had a longer PFS (p=0.050) with a HR of 0.83 (0.69-1.00) and a median PFS of 4.9 m in ND and 4.5 in CD. RR was 54.5% in ND vs 52.9% in CD (p=0.829). Grade 3 or higher AEs of nausea (4.0% vs 14.3%), fatigue (3.4% vs 10.9%), hyponatremia (13.6% vs 30.3%) and hypokalemia (2.3% vs 8.6%) are more frequent in CD. Grade 3 or higher AEs of neutrophils (82.5% vs 70.3%) and platelets (9.0% vs 0.0%) are more frequent in ND, but there was no difference in grade 3 or higher febrile neutropenia (13.6% vs 15.4%). Treatment related deaths occurred in 4 and 3 pts in ND and CD, respectively.
Conclusion:
ND showed a significantly longer OS as compared to CD with different toxicity profile. ND will be considered as a new standard treatment for advanced or relapsed SqLC. Clinical trial information: UMIN000002015.
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ORAL01.02 - Therapy of Advanced Metastatic Lung Cancers with an Anti-Trop-2-SN-38 Antibody-Drug Conjugate, IMMU-132: Interim Phase II Clinical Results (ID 930)
10:45 - 12:15 | Author(s): R. Camidge, A.N. Starodub, A. Ocean, W.A. Messersmith, A. Bardia, S.S. Thomas, G. Masters, R. Heist, P. Maliakal, S. Govindan, R.M. Sharkey, F.E. Wilhelm, D.M. Goldenberg, M.J. Guarino
- Abstract
- Presentation
Background:
Sacituzumab govitecan (IMMU-132) is a new Antibody Drug Conjugate (ADC) comprising SN-38, the active metabolite of the topoisomerase I inhibitor, camptothecin (irinotecan), conjugated to an anti-Trop-2 humanized antibody at a high drug-antibody ratio (7.6). In vitro and in vivo preclinical data suggest that IMMU-132 delivers up to 136-fold more SN-38 than its parental drug, irinotecan, in a human cancer xenograft. Trop-2 is widely expressed in most epithelial cancers, including non-small and small-cell lung cancers (NSCLC and SCLC).The safety and efficacy of this new ADC is being examined in advanced metastatic lung cancers.
Methods:
A Phase II clinical trial (ClinicalTrials.gov, NCT01631552) is ongoing in subsets of previously-treated patients with metastatic lung cancer, administering IMMU-132 on days 1 and 8 of 21-day treatment cycles. A phase 1 run-in phase selected 8 and 10 mg/kg weekly dosage as safe for tumor cohort phase 2 expansion. Treatment is continued based on tolerance or until progression, with safety and response assessments made every week and 8-12 weeks, respectively.
Results:
Forty-four lung cancer patients were given IMMU-132 doses at 8 mg/kg (N = 23) or 10 mg/kg (N = 21); 38 patients (18 NSCLC and 20 SCLC) are assessable for efficacy. Patients were heavily pretreated (median of 3 prior lines). Objective tumor responses (all partial responses by RECIST1.1) and median progression-free survival (PFS) are reported below per tumor. These studies are being expanded.
IMMU-132 was well tolerated with limited grade 3/4 toxicities above the 3% threshold per patient. Neutropenia was the only Grade 3/4 toxicity (G3, 14%; G4, 7%) together with hyponatremia (G3, 2%; G4, 2%). Other drug-related G3 toxicities included diarrhea (7%), anemia (5%), leukopenia (5%), hyperglycemia (5%) and atrial fibrillation (5%); no patient developed antibodies to the conjugate.Tumor type Prior lines of therapy: median (range) Objective Response Rate (PR) Median PFS (maturity) in months NSCLC (N=18) 3 (1-8) 33% 5.4 (56%) SCLC (N=20) 2.5 (1-7) 25% 2.4 (70%)
Conclusion:
Repeated cycles of IMMU-132 monotherapy are well tolerated. Objective response rate and progression-free survival data in previously-treated metastatic lung cancer (5.4 months in NSCLC) are encouraging and warrant further evaluation of IMMU-132 in these lung cancers.
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ORAL01.03 - A Randomized Phase 2 Trial of Vintafolide and Docetaxel in Folate-Receptor Positive (FR+) Advanced NSCLC Patients: Final Efficacy Results (ID 1600)
10:45 - 12:15 | Author(s): N. Hanna, E. Juhasz, C. Cainip, O. Gladkov, Ó. Juan Vidal, R. Ramlau, O.J. Vidal, R. Lal, J. Symanowski, R. Clark, W. Harb
- Abstract
- Presentation
Background:
Vintafolide (folic acid-vinca alkaloid conjugate) binds to the folate receptor (FR), which is overexpressed in approximately 80% of patients with NSCLC, including patients with squamous cell and adenocarcinoma. Using the molecular imaging agent 99mTc-etarfolatide for SPECT imaging, the FR status of malignant lesions can be determined. Vintafolide has demonstrated single agent activity in patients with advanced NSCLC whose tumors all expressed FR [FR(100%)] compared to patients not FR(100%) (Edelman et al, 2012).
Methods:
This study randomized patients with advanced NSCLC whose tumors were FR(100%) to vintafolide, vintafolide + docetaxel, or docetaxel. Key eligibility criteria: age ≥18 years; 1 prior systemic therapy for advanced disease; ECOG PS 0-1. Patients underwent [99m]Tc-etarfolatide SPECT screening for FR assessment. Vintafolide (2.5 mg) was administered on days 1, 4, 8, 11 every 21 days and docetaxel (75 mg/m[2]) on day 1 every 21 days. The primary endpoint was progression-free survival (PFS). Pre-specified PFS comparisons were performed for vintafolide vs docetaxel and vintafolide+docetaxel vs docetaxel in all patients as well as those with adenocarcinoma. Significance testing for each PFS analysis was one-sided without adjustment for multiplicity (alpha=0.10). Overall survival (OS) was a secondary endpoint.
Results:
Over 14 months, 199 FR(100%) patients were randomized and treated (vintafolide: 63; vintafolide+docetaxel: 68; docetaxel: 68). Patient and disease characteristics were well-balanced between arms. The vintafolide+docetaxel arm met the primary endpoint of superior PFS over the docetaxel arm in all patients regardless of histology (17.0% censored; unstratified Cox model hazard ratio [HR] =0.75; unstratified one-sided p-value=0.0696) as well as in the prespecified 133 patient adenocarcinoma subgroup (18.8% censored; HR=0.73; p-value=0.0899). Trends in OS favored the vintafolide+docetaxel arm over the docetaxel arm in all patients (37.7% censored; HR=0.88; p-value=0.2874) and showed the greatest benefit in the adenocarcinoma subgroup (42.8% censored; HR=0.70; p-value=0.1018). The single-agent vintafolide arm was not superior to docetaxel. Vintafolide+docetaxel treatment was associated with more neutropenia (all grades: 77% versus 62%), febrile neutropenia (13% versus 6%), and peripheral neuropathy (34% versus 21%) compared to docetaxel alone.
Conclusion:
The addition of vintafolide to docetaxel resulted in a statistically significant improvement in PFS in FR(100%) NSCLC patients regardless of histology (PFS HR= 0.75) and in the adenocarcinoma subset (PFS HR= 0.73). Additionally, there was a trend towards improvement in OS in all patients regardless of histology (OS HR= 0.88) and in the adenocarcinoma subset (OS HR= 0.70). Vintafolide +docetaxel was generally well tolerated, although rates of neutropenia, neutropenic fever, and neuropathy were higher than with docetaxel alone. Final survival results will be presented at the conference.
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ORAL01.04 - Discussant for ORAL01.01, ORAL01.02, ORAL01.03 (ID 3289)
10:45 - 12:15 | Author(s): M. Boyer
- Abstract
- Presentation
Abstract not provided
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ORAL01.05 - Phase I/II Dose Escalation Study of Immunoconjugate L-DOS47 as a Monotherapy in Non-Squamous Non-Small Cell Lung Cancer Patients (ID 3272)
10:45 - 12:15 | Author(s): D. Kowalski, C. Szczylik, A. Szczesna, R. Ramlau, E. Wiatr, H. Chao, S. Demas, K. Roszkowski-Sliz
- Abstract
- Presentation
Background:
L‑DOS47, a cancer therapeutic designed to exploit the acidic tumour extracellular environment, is a protein conjugate consisting of a urease conjugated to a camelid monoclonal antibody (AFAIKL2) that is targeted to the CEACAM6 antigenic tumour marker. The AFAIKL2 antibody serves as a targeting agent to deliver the enzyme to the tumor sites while the urease enzyme converts urea, an abundant natural metabolite, into ammonia and generates a local pH increase. The combined effect of ammonia toxicity and pH increase is cytotoxic to cancer cells in culture and in xenograft models. This first in human study of L‑DOS47 was designed to define the maximum tolerated dose of multiple doses of L-DOS47 administered intravenously to patients with non-squamous NSCLC when given as a monotherapy.
Methods:
Stage IIIb or IV histologically confirmed non-squamous NSCLC patients (aged ≥18 yrs, ECOG PS ≤2) receive multiple cycles of L-DOS47 during the study treatment period. L-DOS47 is administered once weekly over 14 days followed by 7 days rest in each treatment cycle. Patients are recruited into cohorts and received the same dose of L-DOS47 on Days 1 and 8 of each treatment cycle. Dose levels of L-DOS47 are escalated in further cohorts following a review of safety data by the Trial Steering Committee.
Results:
Thirty-three (33) pts (median age 61, 58% male) were enrolled in the first ten cohorts (dose levels: 0.12, 0.21, 0.33, 0.46, 0.59, 0.78, 1.04, 1.38, 1.84, 2.45 µg/kg) in four Polish centers. L-DOS47 was well tolerated at the dose levels reviewed. No DLTs were reported. Adverse events reported to date were expected for the population under study. None of the patients treated to date have had a partial or complete response as defined by RECIST v1.1. Sixteen (16) patients had an overall response of stable disease after completing two cycles of L-DOS47. One patient in cohort 9 was dosed for 9 cycles without disease progression.
Conclusion:
L-DOS47 monotherapy is well tolerated at dose levels up to 2.45 µg/kg. ClinicalTrials.gov identifier: NCT02340208
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ORAL01.06 - S-1 and Cisplatin versus Docetaxel and Cisplatin in Patients with Untreated Advanced NSCLC: An Randomised, Multicenter, Phase 3 Trial (ID 2734)
10:45 - 12:15 | Author(s): Y. Shi, M. Wang, J. He, J. Chang, B. Han, X. Liu, G. Chen, C. Zhou, J. Liu, H. Pan, C. Huang, S. Zhang, J. Feng, X. Lin, J. Wang, J. Huang, F. Li, S. Qin, Z. Wang, L. Wang, N. Xu
- Abstract
- Presentation
Background:
Platinum-based doublet chemotherapy is the standard chemotherapeutic regimen for treatment-naïve advanced non-small cell lung cancer (NSCLC). S-1, an oral fluoropyrimidine, combined with carboplatin or cisplatin (CDDP) has demonstrated the non-inferiority to the standard platinum doublet chemotherapy in Japanese NSCLC patients. However, its effectiveness in Chinese NSCLC patients is uncertain. The purpose of this study is to compare the efficacy and safety of these chemotherapeutic regimens in Chinese NSCLC patients.
Methods:
We did this randomized controlled study in 21 sites in China. Eligible patients were those aged 18-70 years who was histologically or cytologically confirmed with locally advanced or metastatic NSCLC with no prior radiotherapy, molecular targeted therapy or chemotherapy. Patients were randomized to receive either S-1 orally 80 mg/m[2]/day (40 mg/m[2]2 b.i.d., 80–120 mg/day) with 60 mg/m[2] CDDP on day 8 every 5 weeks (SP) or docetaxel and CDDP (both 75 mg/m[2]) on day 1 every 3 weeks (DP) for up to 6 cycles. Randomisation was stratified by centre, pathological classification, disease stage and gender. The primary endpoint was progression free survival (PFS), analyzed in the full analysis set. The study is registered at ClinicalTrials.jp, number Japic CTI-111479.
Results:
Between March 2011 and November 2012, 246 patients from 21 institutions in China were randomly assigned and received SP or DP treatment (124 vs 122) with 18-month follow-up period from the last patient randomized. In the SP and DP group, median PFS was 5.9 and 5.7 months (HR=0.68; 95% CI, 0.48-0.96) respectively, median overall survival was 19.1 and 14.8 months, respectively (HR=0.84; 95% CI, 0.61-1.14). The most common grade 3 or worse adverse events in both treatment groups were neutropenia 3.3% vs 55.1%, leukopenia 1.7% vs 39.0%, and febrile neutropenia 0.8% vs 5.9%, of 121 patients in the SP group and of 118 patients in the DP group, respectively.
Conclusion:
The efficacy of SP was non-inferior to DP with a better safety profile. SP would be a new standard first-line chemotherapy regimen for Chinese patients with advanced NSCLC.
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ORAL01.07 - Discussant for ORAL01.05, ORAL01.06 (ID 3290)
10:45 - 12:15 | Author(s): J. Spicer
- Abstract
- Presentation
Abstract not provided
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ORAL 20 - Chemoradiotherapy (ID 124)
- Event: WCLC 2015
- Type: Oral Session
- Track: Treatment of Locoregional Disease – NSCLC
- Presentations: 7
- Moderators:G. Blumenschein, J.Y. Chang
- Coordinates: 9/08/2015, 10:45 - 12:15, 201+203
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ORAL20.01 - A Systematic Review of Carboplatin-Paclitaxel versus Cisplatin-Etoposide Concurrent with Thoracic Radiation for Stage III NSCLC Patients (ID 600)
10:45 - 12:15 | Author(s): C. Steuer, M. Behera, K.A. Higgins, N. Saba, D. Shin, S. Pakkala, R. Pillai, T.K. Owonikoko, W.J. Curran, C.P. Belani, F. Khuri, S.S. Ramalingam
- Abstract
- Presentation
Background:
The two most commonly used chemotherapy regimens deployed concurrently with thoracic radiation (RT) for patients with unresectable IIIA and IIIB non-small cell lung cancer (NSCLC) are carboplatin/paclitaxel (CP) and cisplatin/etoposide (CE). Because there are no prospective comparisons of these two regimens in this setting, we conducted a systematic review of published trials to compare outcomes and toxicities between CE and CP.
Methods:
Studies which enrolled stage III patients receiving RT with CP or CE were identified using electronic databases (MEDLINE, EMBASE, and Cochrane library) and meeting abstracts. Trials were excluded if they were phase I, enrolled less than 10 pts, or included surgical resection. A systematic analysis of extracted data was performed using Comprehensive Meta Analysis (Version 2.2) software using random and fixed effect models. Clinical outcomes were compared using point estimates for weighted values of median overall survival (OS), progression free survival (PFS), response rate (RR) and toxicities. Two-tailed T-test with a significance level of 0.05 was used for all comparisons.
Results:
3194 patients were included from 32 studies in the CE arm, and 3789 patients from 51 studies in CP. Baseline characteristics of patients on the CE arm versus CP arm were: median age 61 vs. 63 years, male 67.6% vs. 78%, squamous histology 39% vs. 40%, and median radiation dose 62 Gy vs. 63 Gy. There was no significant difference in response rates between CE and CP (65% vs. 56%, p =0.6), respectively. There was no significant difference in median progression free survival (11.5m vs. 9.3m p =0.2), overall survival (19.8m vs. 18.4m, p=0.48), 1-year survival rate (66% vs. 65%, p=0.8), or 3-year survival rate (31% vs. 25%, p=0.4) for CE vs. CP. CE was associated with higher grade 3/4 hematological toxicities than CP, such as neutropenia (53% vs. 23% p<0.0001), thrombocytopenia (14% vs. 6% p=0.001), anemia (16% vs. 8% p=0.06), as well as grade 3/4 nausea/vomiting (20% vs. 9% p=0.018), while rates of grade 3/4 pneumonitis and esophagitis were similar.
Conclusion:
CE and CP regimens were associated with comparable efficacy when used with concurrent radiotherapy for stage III unresectable NSCLC pts. The toxicity profile favored the CP regimen.
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ORAL20.02 - Safety Results of the Consolidation Phase of a Phase III (PROCLAIM): Pemetrexed, Cisplatin or Etoposide, Cisplatin plus Thoracic Radiation Therapy followed by Consolidation Cytotoxic Chemotherapy in Locally Advanced Nonsquamous Non-Small Cell Lung Cancer (ID 645)
10:45 - 12:15 | Author(s): R. Govindan, S. Senan, A. Brade, J. Vansteenkiste, F. Mornex, H.J. Ross, J.P. Van Meerbeeck, C. Hennequin, N. Dickgreber, Y. Wu, J.P. Agarwal, K. Syrigos, F. Griesinger, B. Parente, M. Provencio, A. Hossain, B. San Antonio, J.A. Treat, A. Koustenis, N. Chouaki, E. Vokes
- Abstract
- Presentation
Background:
Standard treatment for inoperable stage III non-small cell lung cancer (NSCLC) is concurrent chemoradiotherapy. However, many patients die from recurrent disease, indicating that new treatment strategies are needed.
Methods:
PROCLAIM is a phase III trial comparing overall survival in patients with unresectable stage III nonsquamous NSCLC receiving pemetrexed+cisplatin (PemCis) and concurrent radiotherapy for 3 cycles followed by 4 cycles of pemetrexed consolidation (Arm A) versus etoposide+cisplatin (EtoCis) and concurrent radiotherapy for 2 cycles followed by consolidation with a platinum-based doublet of choice for up to 2 cycles (Arm B). Possible consolidation therapies in Arm B were EtoCis, vinorelbine+cisplatin (VinCis), and paclitaxel+carboplatin (PacCarb). Overall efficacy and safety results for the intent-to-treat population will be presented in a separate disclosure. Safety was a secondary objective. Interim safety results for the concurrent phase were previously presented. Here we present safety results for the consolidation phase. Treatment-emergent adverse events (TEAEs) were assessed according to the Common Terminology Criteria for Adverse Events (v3.0, CTCAE). TEAE incidences were compared using Fisher’s exact test (two-sided α=0.05).
Results:
Of 598 randomized patients, 555 were treated in the concurrent phase (Arm A: N=283; Arm B: N=272), most of whom (Arm A: n=229 [80.9%]; Arm B: n=202 [74.3%]) continued on to the consolidation phase (Arm B patients: EtoCis [33.5%], PacCarb [26.8%], VinCis [14.0%]). Baseline characteristics, including age, gender, performance status, smoking status, stage, and origin, were well-balanced across arms. Percentages of patients in Arm A completing ≥2, ≥3, and 4 consolidation cycles were 95.2%, 84.3%, and 73.4%, respectively. Percentages of patients in Arm B completing 2 consolidation cycles (maximum) were EtoCis (89.0%), PacCarb (93.2%), and VinCis (86.8%). Mean dose intensities for pemetrexed, etoposide, vinorelbine, cisplatin, paclitaxel, and carboplatin were 95.4%, 94.0%, 84.2%, 91.2%, 88.7%, and 92.7%, respectively. More patients in Arm B, compared to Arm A, experienced dose reductions, dose omissions, and cycle delays. Patients in Arm B reported more grade 3/4/5 drug-related TEAEs than Arm A (51.0% versus 31.0%, p<0.001; Table). Rates of drug-related serious AEs were similar between groups (Arm A: 14.4%; Arm B: 13.4%).Drug-related Grade 3/4/5 TEAEs Occurring in ≥2% of Patients (or of Clinical Relevance) in the Consolidation Phase
CTCAE Arm A (N=229) n (%) Arm B (N=202) n (%) Neutrophils 27 (11.8) 76 (37.6)* Leukocytes 19 (8.3) 29 (14.4) Hemoglobin 6 (2.6) 9 (4.5) Platelets 5 (2.2) 10 (5.0) Febrile neutropenia 7 (3.1) 7 (3.5) Lymphopenia 8 (3.5) 5 (2.5) Pneumonitis/pulmonary infiltrates 5 (2.2) 2 (1.0) Fatigue 2 (0.9) 4 (2.0) Pneumonia 5 (2.2) 0 Esophagitis 0 3 (1.5) *p<0.001, Fisher’s exact test. Note: Of the TEAEs listed here, only one case (0.4%, Arm A, pneumonia) was grade 5.
Conclusion:
During the PROCLAIM consolidation phase, most patients were able to complete the planned number of cycles in either arm, with the highest dose intensity corresponding to pemetrexed. Pemetrexed consolidation had a significantly lower incidence of drug-related grade 3/4/5 TEAEs than the platinum doublets in Arm B. A more detailed analysis of Arm B (by treatment regimen) is underway.
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ORAL20.03 - Radiation Dose Escalation in Patients with Locally Advanced Non-Small Cell Lung Cancer; 60 Month Follow-Up of a Randomized Phase II Trial (ID 1190)
10:45 - 12:15 | Author(s): I. Walraven, M. Van Den Heuvel, E. Schaake, W. Uyterlinde, J. De Jong, J.G. Aerts, F. Koppe, H. Codrington, P. Kunst, E. Dieleman, P. Van De Vaart, M. Verheij, J. Belderbos
- Abstract
- Presentation
Background:
Concurrent chemoradiotherapy imposes beneficial effects on overall survival (OS) in patients with locally advanced non-small cell lung cancer (NSCLC). Nonetheless, the optimal radiation scheme still needs to be identified. The RTOG 0617 trial showed that patients receiving a high dose radiation scheme (37 x 2 Gy) had a significant shorter median OS (22.9 months) as compared to patients receiving a conventional 30 x 2 Gy radiation scheme (28.7 months). Dose escalation using hypo-fractionation however seems promising and might contribute to a better OS. We investigated long term OS in locally advanced NSCLC patients treated with concurrent chemoradiotherapy, using a hypo-fractionation scheme of 24 x 2.75 Gy +/- Cetuximab.
Methods:
A 2-armed phase II, multi-center study (NTR2230) was performed with the initial aim to assess the effect of the addition of Cetuximab to concurrent chemoradiotherapy in locally advanced NSCLC patients. Arm A received high dose radiotherapy (24 x 2.75 Gy) and concurrent daily low-dose cisplatin (6 mg/m[2]). Arm B received an identical treatment regimen with the addition of weekly Cetuximab (400 mg/m[2] loading dose one week prior to radiotherapy followed by weekly 250 mg/m[2]). Mortality follow-up information was completed until January 2015. Overall survival (OS) rates were calculated as time from randomization until death from any cause. Kaplan-Meier survival curves were plotted and 1-, 2- and 5-year OS proportions were calculated.
Results:
Between February 2009 and May 2011, 102 patients were randomly allocated in two arms; 51 patients (50%) in arm A and 51 patients (50%) in arm B. Follow-up information was available for 101 patients (99%). Median OS was 33.0 months (interquartile (IQ) range 20.0 to 46.0) and did not significantly differ between the two arms; 33.0 months (IQ-range 13.8 to 52.2) in Arm A and 30.0 months (IQ-range 15.3 to 44.7) in Arm B (Figure 1). 1-,2- and 5-year OS was 75.5%, 59.8% and 36.6%, respectively. Figure 1
Conclusion:
In this 2-armed phase II trial in NSCLC patients receiving concurrent chemoradiotherapy, the addition of Cetuximab to concurrent chemoradiotherapy did not improve 60-month OS in unselected patients with locally advanced NSCLC, in line with the RTOG 0617. However, the median OS was remarkably high when compared to the RTOG 0617: 30 and 33 months versus 23 and 29 months, respectively. Furthermore, 5-year OS was still 36.6%. Dose escalation using hypo-fractionation of 2.75 Gy per fraction might be one of the factors contributing to extended OS in patients with locally advanced NSCLC.
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ORAL20.04 - Discussant for ORAL20.01, ORAL20.02, ORAL20.03 (ID 3288)
10:45 - 12:15 | Author(s): G.M.M. Videtic
- Abstract
- Presentation
Abstract not provided
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ORAL20.06 - Outcomes of Intensity Modulated and 3D-Conformal Radiotherapy for Stage III Non-Small Cell Lung Cancer in NRG Oncology/RTOG 0617 (ID 938)
10:45 - 12:15 | Author(s): S.G. Chun, C. Hu, H. Choy, R.U. Komaki, R.D. Timmerman, S.E. Schild, J.A. Bogart, M.C. Dobelbower, W. Bosch, J.M. Galvin, V.S. Kavadi, S. Narayan, P. Iyengar, C.G. Robinson, R.B. Wynn, A. Raben, M.E. Augspurger, R.M. Macrae, R. Paulus, J.D. Bradley
- Abstract
Background:
Intensity modulated radiation therapy (IMRT) has the potential to improve target coverage and spare toxicity in locally-advanced non-small cell lung cancer (NSCLC). However, the effect of IMRT on outcomes for NSCLC has not previously been assessed in a large prospective cooperative group clinical trial.
Methods:
A secondary analysis was performed in patients with stage III NSCLC in NRG/RTOG 0617, a randomized phase III comparison of standard-dose (60 Gy) versus high-dose (74 Gy) chemoradiotherapy +/- cetuximab. Radiotherapy (RT) technique was stratified by IMRT and 3D-conformal radiotherapy (3D-CRT). Baseline prognostic and RT dosimetric parameters were compared between IMRT and 3D-CRT after adjusting for RT dose levels and cetuximab use. The prognostic value of RT technique with respect to toxicity and efficacy was assessed through multivariate logistic regression (MVA) and Cox proportional hazards model after controlling for RT dose level, cetuximab use and other factors.
Results:
Of the 482 eligible patients treated with RT, 53% and 47% were treated with 3D-CRT and IMRT, respectively. The IMRT group had more stage IIIB (38.6 vs. 30.3%, P = 0.056), larger PTVs (mean 486 vs. 427 mL, P = 0.005), and larger PTV:lung ratio (mean 0.15 vs. 0.13, P = 0.013). In spite of larger PTV volumes, IMRT was associated with lower lung V20 (P = 0.08), and lower heart doses (V5, V20, V40) than 3D-CRT. In turn, IMRT was associated with a lower rate (3.5 versus 7.9%) of Grade 3+ pneumonitis (P = 0.0653). On MVA, the lung V20 significantly predicted grade 3+ pneumonitis, while the lung V5 and mean lung doses did not. Larger heart V40 was associated with worse OS (HR=1.013, P < 0.001), and the heart V40 was significantly lower in patients treated with IMRT. Patients treated with IMRT were also more likely (37 versus 29%) to receive full doses of consolidative chemotherapy (P = 0.05).
Conclusion:
Although IMRT was used to treat larger and less favorable tumors in RTOG 0617, it was associated with reduced risk of Grade 3+ pneumonitis and higher likelihood of receiving full doses of consolidative chemotherapy. The heart V40, shown to be highly prognostic for survival, can be substantially reduced with IMRT compared to 3D-CRT.
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ORAL20.07 - Survival Impact of Post-Operative Therapy Modalities after Incomplete and Complete Surgical Resection for Non-Small Cell Lung Cancer in the US (ID 1417)
10:45 - 12:15 | Author(s): M.P. Smeltzer, C.C. Lin, X. Yu, A. Jemal, R.U. Osarogiagbon
- Abstract
- Presentation
Background:
Incomplete resection of potentially curable Non-Small Cell Lung Cancer (NSCLC) is a significantly negative clinical event for which adjuvant radiotherapy, chemotherapy, or combined chemo-radiotherapy is often used to reduce mortality risk. After complete (R0) resection, randomized controlled trials and the PORT meta-analysis show radiotherapy to be harmful to patients with stage I-II disease, and of marginal benefit in patients with N2-positive stage IIIA. After incomplete resection (R1/R2), current National Comprehensive Cancer Network (NCCN) guidelines recommend radiotherapy for stage IA/IB and chemo-radiotherapy for patients with stage IIA-IIIA. Adjuvant therapy recommendations after R1/R2 resection have never been verified.
Methods:
With the objective of validating NCCN post-operative therapy guidelines, we evaluated patients with surgically resected pathologic stage I-IIIA NSCLC in the National Cancer Data Base from 2004-2011. Recipients of pre-operative adjuvant therapy and those with no lymph nodes examined were excluded. Post-operative therapy modalities were classified as chemotherapy, radiotherapy, chemo-radiotherapy, or no treatment. Analyses were adjusted for patient demographic, clinical, and surgical characteristics, as well as institutional characteristics. Analyses were conducted by margin status and stage groups based on NCCN classifications (Table I). Unadjusted stage-specific 5-year overall survival (OS) estimates were calculated based on the Kaplan-Meier method and compared across post-treatment modalities with the log-rank test. Survival was modeled with Extended Cox Regression to adjust for all covariates and allow for non-proportional hazards.
Results:
Among 98,176 NSCLC patients who underwent curative-intent surgery during 2004-2011, 48% were male, 79% white, 34% privately insured, and 58% Medicare insured, with a median age of 68 years. The 5-year OS estimates by treatment modality are shown in Table I (NCCN recommendations highlighted). Margin negative patients with stage IA or IB/IIA who received post-operative radiotherapy had significantly lower OS compared to those with no treatment (both p-values<0.0001). We also observed lower OS with post-operative radiotherapy in margin positive patients with stage IA (p-value=0.0006) and IB/IIA (p-value=0.0302). Survival was significantly higher in persons with stages IB-IIIA who received post-operative chemotherapy compared to no treatment (all p-values<0.0001). Fully adjusted modeling analyses (not shown) yielded similar results.5 Year Survival (P-Value) NCCN Categorized Group Margin Positive Margin Negative Stage IA (T1ab,N0) No Treatment 60%(Ref) 71%(Ref) Chemo-Only 64%(0.86) 74%(0.33) Radiotherapy-Only 24%(0.0006) 47%(<0.0001) Chemo+Rad 44%(0.17) 43%(<0.0001) (N=458) (N=41279) Stage IB (T2a,N0) & Stage IIA (T2b,N0) No Treatment 48%(Ref) 57%(Ref) Chemo-Only 66%(0.0002) 69%(<0.0001) Radiotherapy-Only 30%(0.0302) 41%(<0.0001) Chemo+Rad 39%(0.28) 48%(<0.0001) (N=1016) (N=29111) Stage IIA (T1ab-T2a,N1) & Stage IIB (T3,N0;T2b,N1) No Treatment 27%(Ref) 39%(Ref) Chemo-Only 35%(<0.0001) 55%(<0.0001) Radiotherapy-Only 26%(0.84) 29%(<0.0001) Chemo+Rad 36%(<0.0001) 43%(0.0194) (N=1549) (N=15543) Stage IIIA (T1-3,N2;T3,N1) No Treatment 15%(Ref) 26%(Ref) Chemo-Only 25%(0.0013) 41%(<0.0001) Radiotherapy-Only 11%(0.76) 19%(0.0551) Chemo+Rad 26%(<0.0001) 39%(<0.0001) (N=1109) (N=8111)
Conclusion:
In patients with negative margins, results from the NCDB are consistent with randomized clinical trials and stage-specific NCCN post-operative adjuvant therapy recommendations. However, the NCCN recommendation of post-operative adjuvant radiotherapy for patients with early stage NSCLC with a positive resection margin is not supported by our results and should be further investigated in a randomized clinical trial.
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ORAL20.08 - Discussant for ORAL20.06, ORAL20.07 (ID 3353)
10:45 - 12:15 | Author(s): A. Bezjak
- Abstract
- Presentation
Abstract not provided
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