A phase III trial of carboplatin, paclitaxel, and thoracic radiation therapy with or without thalidomide in patients with stage III non-small cell carcinoma of the lung (NSCLC): E3598

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 7503-7503 ◽  
Author(s):  
J. H. Schiller ◽  
S. E. Dahlberg ◽  
M. Mehta ◽  
D. H. Johnson
Keyword(s):  
Overall Survival ◽  
Radiation Therapy ◽  
Angiogenesis Inhibitor ◽  
Data Monitoring Committee ◽  
Phase Iii ◽  
Stage Iii ◽  
Thoracic Radiation ◽  
Stage Iii Nsclc ◽  
Clinically Significant ◽  
Grade 3

7503 Background: Thalidomide (T) is an oral angiogenesis inhibitor with anti-tumor activity in hematological malignancies. Given that antiangiogenic drugs such as bevacizumab have proven activity in advanced NSCLC, ECOG conducted a phase III study to compare the effects of the addition of thalidomide to paclitaxel/carboplatin/radiation therapy (PC/RT) on overall survival (OS) in pts with newly diagnosed stage III NSCLC. Secondary endpoints included time to progression (PFS) and toxicity. Methods: Pts were required to have inoperable stage IIIA or IIIB (no pleural effusion) NSCLC and a PS of 0 or 1. Pts were randomized to receive 2 cycles of P (225 mg/m2)+ C (AUC=6) every 3 wks or PC + thalidomide starting at 200 mg daily with the possibility of dose escalation. This was followed by weekly C (AUC=2), P (45 mg/m2) and concurrent RT (60 Gy) ± T. Pts on PC/RT + T continued thalidomide for 24 mo. or until disease progression. Results: 277 eligible pts were randomized to PC/RT and 272 pts to PC/RT + T. Median age was 63; 61% of pts had stage IIIB disease, 35% had squamous histology, and 46% were PS 0. The third planned interim analysis was conducted with 403 of 506 planned deaths (73.9%) for full analysis and the trial was stopped early by the ECOG Data Monitoring Committee for futility. The median overall survival for the no T arm was 15.3 mo. (12.4–20.2 mo.) compared to 16.0 mo for the T arm (14.4–18.3 mo.); hazard ratio = 0.985 (0.81–1.19); p = 0.88. Median PFS for the no T arm was 7.6 mo. (6.6–8.7 mo.) compared to 8.0 mo. for the T arm (7.1–9.1 mo.), p>0.05. The most common toxicity on both arms was myelosuppression. 11% of pts on the T arm had a grade 3–5 thrombosis/embolism, compared to <3% on the no T arm. Conclusions: The addition of thalidomide to PC/RT in pts with stage III NSCLC does not provide a clinically significant benefit. [Table: see text]

Safety assessment for the combination of docetaxel, carboplatin, and thoracic radiotherapy in unresectable stage III non-small cell lung cancer (NSCLC): A report of the first 100 patients treated with chemoradiation on D0410

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7701-7701
Author(s):  
J. R. Rigas ◽  
M. S. Rubin ◽  
J. M. Waples ◽  
K. H. Dragnev ◽  
D. M. Zimmerman ◽  
...  
Keyword(s):  
Safety Information ◽  
Data Monitoring Committee ◽  
Phase Iii ◽  
Stage Iii ◽  
Efficacy Evaluation ◽  
Phase Iii Trial ◽  
Total Lung Volume ◽  
Unresectable Stage ◽  
Stage Iii Nsclc ◽  
Grade 3

7701 Background: Concurrent chemoradiotherapy (chemoRT) is the preferred treatment for patients with unresectable stage III NSCLC. Limited safety information is available on the use of concurrent docetaxel, carboplatin and thoracic RT. We report the safety information on the initial 100 patients (pts) treated with this chemoRT as part of an ongoing US randomized phase III trial (D0410) evaluating the role of erlotinib/placebo following this concurrent chemoRT treatment. The sample size is 400 pts and the primary endpoint is progression-free survival. Methods: Pts with unresectable pathologically confirmed stage III NSCLC are randomized to receive either erlotinib 150 mg or placebo orally daily for 2 years following concurrent chemoRT with docetaxel 20 mg/m2, carboplatin AUC=2 intravenously weekly for 6 wks with thoracic RT of at least 61 Gy in 33 fractions over 6.5 weeks. The planned total lung volume exceeding 20 Gy (V20) was less than 32%. Only the chemoradiation safety information is being reported. This data was reviewed by an independent safety and data monitoring committee. Results: Pt characteristics; 59% males, median age 69 years (range 38 to 86), 21% adenocarcinoma, 48% squamous cell, 94% ECOG PS0–1, 49% stage IIIA, 15% weight loss = 10%. Of 600 planned chemotherapy treatments, 492 were administered (93 wk 1, 85 wk 2, 82 wk 3, 81 wk 4, 77 wk 5, 74 wk 6). There were 25 chemotherapy dose reductions; most commonly for esophagitis (8), neutropenia (5), renal dysfunction (3), hypersensitivity (2). There were no treatment-related deaths. There were 25 grade 3 and 3 grade 4 treatment-related adverse events. The most common grade 3/4 events were esophagitis (6), fatigue (3), odynophagia (2), neutropenia (1), thrombocytopenia (1), dematitis (1). Conclusions: This concurrent chemoradiation regimen appears to be safe. Enrollment to the phase III trial continues. There is a planned interim efficacy evaluation at 150 events (deaths or disease progression). Funded in part by Sanofi- Aventis, Genentech, and OSI Pharmaceuticals. [Table: see text]

Updated analysis of SWOG 0023: A randomized phase III trial of gefitinib versus placebo maintenance after definitive chemoradiation followed by docetaxel in patients with locally advanced stage III non-small cell lung cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7513-7513 ◽  
Author(s):  
K. Kelly ◽  
K. Chansky ◽  
L. E. Gaspar ◽  
J. R. Jett ◽  
Y. Ung ◽  
...  
Keyword(s):  
Median Survival ◽  
Alternative Hypothesis ◽  
Locally Advanced ◽  
Phase Iii ◽  
Stage Iii ◽  
Definitive Treatment ◽  
Logrank Test ◽  
Ideal Agent ◽  
Thoracic Radiation ◽  
Grade 3

7513 Background: Early clinical studies with gefitinib (G) showed promising efficacy and mild toxicity in patients (pts) with advanced NSCLC. Thus, G was an ideal agent to evaluate in a maintenance setting in stage III disease following definitive treatment. Methods: Untreated pts with stage III NSCLC, a PS of 0–1 and adequate organ function were eligible. Patients received the SWOG 9504 core regimen (cisplatin 50 mg/m2, d1 & 8 plus etoposide 50 mg/m2 day 1–5, every 28 days for 2 cycles with concurrent thoracic radiation, 1.8–2 Gy fractions/day, total dose 61 Gy, followed by 3 cycles of docetaxel 75 mg/m2). Non- progressing pts were randomized to G 250 mg per day or placebo (P) until disease progression, intolerable toxicity or 5 years. The planned sample size was 672, to confer power of 0.89 to detect a 33% increase over the expected median survival of 21 months (one-sided 0.025 level logrank test). Randomization was stratified by stage and histology. Results: Enrollment began in July 2001. An unplanned interim analysis prompted by outside data was conducted in April 2005 and the alternative hypothesis of improved survival was rejected at the 0.0015 level for 243 randomized patients. The study closed and preliminary results were reported (ASCO 2005). Now with a median follow up of 27 months, median survival for the G arm (n=118) was 23 months and was 35 months for the P arm (n=125) (two sided p=0.013). Overall survival for the 571eligible patients was 19 months. ≥ Grade 3 toxicities in the G arm were rash (7%), diarrhea (7%) and pneumonitis (3%). Conclusion: In this unselected population G did not improve survival. Decreased survival was due to cancer not G toxicity. Three year survival estimates will be presented. Molecular studies of the EGFR pathway are underway and will be correlated with outcomes. No significant financial relationships to disclose.

scholarly journals Augmentation of Therapy for Combined Loss of Heterozygosity 1p and 16q in Favorable Histology Wilms Tumor: A Children’s Oncology Group AREN0532 and AREN0533 Study Report

2019 ◽  
Vol 37 (30) ◽  
pp. 2769-2777 ◽  
Author(s):  
David B. Dix ◽  
Conrad V. Fernandez ◽  
Yueh-Yun Chi ◽  
Elizabeth A. Mullen ◽  
James I. Geller ◽  
...  
Keyword(s):  
Overall Survival ◽  
Radiation Therapy ◽  
Loss Of Heterozygosity ◽  
Wilms Tumor ◽  
Adverse Outcomes ◽  
Stage I ◽  
Stage Iii ◽  
Rank Test ◽  
Favorable Histology ◽  
Grade 3

PURPOSE In National Wilms Tumor Study 5 (NWTS-5), tumor-specific combined loss of heterozygosity of chromosomes 1p and 16q (LOH1p/16q) was associated with adverse outcomes in patients with favorable histology Wilms tumor. The AREN0533/AREN0532 studies assessed whether augmenting therapy improved event-free survival (EFS) for these patients. Patients with stage I/II disease received regimen DD4A (vincristine, dactinomycin and doxorubicin) but no radiation therapy. Patients with stage III/IV disease received regimen M (vincristine, dactinomycin, and doxorubicin alternating with cyclophosphamide and etoposide) and radiation therapy. METHODS Patients were enrolled through the AREN03B2 Biology study between October 2006 and October 2013; all underwent central review of pathology, surgical reports, and imaging. Tumors were evaluated for LOH1p/16q by microsatellite testing. EFS and overall survival were compared using the log-rank test between NWTS-5 and current studies. RESULTS LOH1p/16q was detected in 49 of 1,147 evaluable patients with stage I/II disease (4.27%) enrolled in AREN03B2; 32 enrolled in AREN0532. LOH1p/16q was detected in 82 of 1,364 evaluable patients with stage III/IV disease (6.01%) in AREN03B2; 51 enrolled in AREN0533. Median follow-up for 83 eligible patients enrolled in AREN0532/0533 was 5.73 years (range, 2.84 to 9.63 years). The 4-year EFS for patients with stage I/II and stage III/IV disease with LOH1p/16 was 87.3% (95% CI, 75.1% to 99.5%) and 90.2% (95% CI, 81.8% to 98.6%), respectively. These results are improved compared with the NWTS-5 updated 4-year EFS of 68.8% for patients with stage I/II disease ( P = .042), and 61.3% for patients with stage III/IV disease ( P = .001), with trends toward improved 4-year overall survival. The most common grade 3 or higher nonhematologic toxicities with regimen M were febrile neutropenia (39.2%) and infections (21.6%). CONCLUSION Augmentation of therapy improved EFS for patients with favorable histology Wilms tumor and LOH1p/16q compared with the historical NWTS-5 comparison group, with an expected toxicity profile.

Final Results of a Single Arm Phase III Multicenter, Open-Label Study of Rituximab Administered by Faster Infusion in Patients with Previously Untreated Diffuse Large-B Cell (DLBCL) or Follicular Non-Hodgkin's Lymphoma (FL)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2703-2703 ◽  
Author(s):  
Shaker R. Dakhil ◽  
Robert Hermann ◽  
Akiko Chai ◽  
Deborah Hurst ◽  
Gregg Fine ◽  
...  
Keyword(s):  
Sample Size ◽  
Cardiac Disease ◽  
Hodgkin's Lymphoma ◽  
Phase Iii ◽  
Stage Iii ◽  
Open Label ◽  
Non Hodgkin's Lymphoma ◽  
Clinically Significant ◽  
Grade 3 ◽  
Infusion Duration

Abstract Abstract 2703 Introduction: For lymphoma patients (pts) receiving rituximab according to the prescribing information the first rituximab infusion typically requires 4−6 hrs and subsequent infusions require 3−4 hrs. Several pilot studies have investigated the feasibility of faster infusion of rituximab, but no phase III trials have prospectively analyzed safety in a larger population. In order to evaluate whether a faster infusion is feasible for the second and subsequent cycles of rituximab plus chemotherapy treatment, a prospective single arm, open-label phase III multicenter single-arm trial was performed to assess the safety of faster rituximab infusion in previously untreated pts with DLBCL and FL. Methods: Previously untreated pts with DLBCL or FL scheduled to receive R-CHOP and R-CVP respectively were eligible for participation in this study. Pts with a history of clinically significant cardiac disease were excluded. Pts received acetaminophen, an antihistamine and the oral steroid component of their chemotherapy regimen before each rituximab infusion. No additional steroid premedication was permitted. The first rituximab infusion was administered at an initial rate of 50 mg/hr and in the absence of toxicity increased by 50 mg/hr to a maximum of 400 mg/hr. Pts with infusion-related SAEs or grade 3/4 IRRs in the first cycle went off study. Rituximab in subsequent cycles was to be administered over a planned duration of 90 minutes: 20% of the total rituximab dose over 30 minutes, and the remaining 80% over the next 60 minutes. The primary outcome of this study was the rate of grade 3/4 IRRs during or within 24 hrs of Cycle 2 Day 1 in pts who received the faster infusion of rituximab. The definition of infusion-related AE required onset within 24 hrs of the start of infusion and encompassed MedDRA terms mapped to a prespecified list of AE terms derived from previous phase III rituximab studies. Secondary endpoints included other AEs, AEs leading to drug discontinuation, deaths, SAEs, and duration of administration (by cycle). Assuming the point estimate of the incidence of grade 3/4 IRRs was no larger than 5%, a sample size of at least 300 pts receiving faster infusion was needed to estimate the incidence with a margin of error of no greater than 2.5%. This sample size also allowed a fatal IRR rate of 1% or higher to be ruled out with a type I error less than 5% if no fatal IRRs were observed in the study. Results: Between July 2008 and November 2010, 451 pts were enrolled at 93 centers in the U.S. 425 pts received the first dose of rituximab at a median infusion duration of 2–0 minutes (92–390 minutes). Fifty-three pts (12.4%) discontinued prior to receiving the faster infusion: 5.6% discontinued the study because of Grade 3/4 IRRs, SAEs (including 5 deaths) and other AEs; and 6.8% discontinued for other reasons. The faster infusion of rituximab was administered starting at cycle 2 to 363 patients (250 R-CHOP, 113 R-CVP). R-CHOP pts had a median age=64 (range 20–86) and stage III-IV=63.4%. R-CVP pts had a median age=65 (range 33–88) and stage III-IV=77.0%. A total of 1764 infusions were administered at the faster rate. The median infusion duration at cycle 2 was 90 minutes (range 60–233) and was maintained over all subsequent cycles. For pts receiving the faster infusion at Cycle 2 Day 1, the rate of grade 3/4 IRR at cycle 2 was 1.1% (4 patients; 95%CI [0.3%, 2.8%]); the events included rash, bronchospasm, hypersensitivity, and abdominal pain. The rate of grade 3/4 IRRs occurring during cycle 2 or beyond was 2.8% (10 patients; 95%CI [1.3%, 5.0%]). IRR of any grade occurred in 38.3% of pts at Cycle 2 Day 1 with a decreased incidence in subsequent cycles. No fatal IRRs were observed. Thirteen deaths occurred on study outside of the infusion period (5 during cycle 1, 8 during or after cycle 2). Conclusion: The target duration of faster infusion was maintained while observing a rate of grade 3/4 IRRs of 1.1% at Cycle 2 and 2.8% at Cycle 2 and beyond with no fatal IRRs. Based on these results, the faster infusion of rituximab in pts without clinically significant cardiac disease who receive the first cycle of rituximab without a grade 3/4 IRR is feasible and associated with a safety profile comparable to historical data for patients with previously untreated DLBCL or FL who receive either R-CHOP or R-CVP. Disclosures: Off Label Use: Rituximab. Treatment of patients with Non-Hodgkin's Lymphoma (NHL). Chai:Genentech: Employment. Hurst:Genentech: Employment. Fine:Genentech: Employment.

Phase III study of cisplatin (P) plus etoposide (E) with concurrent chest radiation (XRT) followed by docetaxel (D) vs. observation in patients (pts) with stage III non-small cell lung cancer (NSCLC): An interim toxicity analysis of consolidation therapy

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7043-7043 ◽  
Author(s):  
P. M. Bedano ◽  
M. Neubauer ◽  
R. Ansari ◽  
R. Govindan ◽  
L. H. Einhorn ◽  
...  
Keyword(s):  
High Rate ◽  
Phase Iii ◽  
Study Entry ◽  
Stage Iii ◽  
Unresectable Stage ◽  
Toxicity Analysis ◽  
Stage Iii Nsclc ◽  
Grade 3 ◽  
Asco Meeting ◽  
Dose Modifications

7043 Background: Concurrent chemo radiotherapy is the standard treatment for pts with unresectable stage III NSCLC. A previously reported phase II study (Gandara et al J Clin Oncol 2003) suggests that consolidation D after concurrent PE/XRT may further improve survival. HOG LUN01–24, is an ongoing phase III clinical trial comparing chemo radiation. A preliminary analysis of the differences in toxicities between PE/XRT with or without consolidation D was performed. Methods: Eligible pts had previously untreated, unresectable stage III NSCLC, ECOG PS 0–1 at time of study entry (and PS 0–2 at the time of randomization), ≤ 5% weight loss in preceding 3 months, FEV-1 > 1 L. Treatment consisted of P 50 mg/m2 days 1, 8, 29, 36 with E 50 mg/m2 days 1–5 and 29–33, given concurrently with chest XRT to 5,940 cGy (180 cGy/day) beginning on day 1. Non-progressive pts were randomized (4–8 weeks after completing PE/XRT) to receive D 75 mg/m2 iv every 21 days for 3 cycles vs. observation. We report an interim toxicity analysis associated to consolidation D. Results: From 3/02 to 12/05 220 have been registered and 149 pts have been randomized to consolidation D (n=73) or observation (n=76). Median age was 63.6 years (range 33–86); male/female 34.1%/65.9%; PS 0/1 at study entry 59.1%/40.9%; stage III A/B 40.6%/59.4%; 50.2% had FEV-1 > 2 (range 1–4.2); 44.3% were current smokers. Randomized pts have PS 0/1/2 44.3%/53%/2.7. Selected grade 3/4 toxicities associated to D include: neutropenia 23.3%, febrile neutropenia 8.2%, and pulmonary toxicity 9.6%. In addition, 26.7% of pts had dose modifications or delays on D arm, 45.2% had at least one grade 3/4 toxicity and 20.5% were hospitalized due to D-related toxicity, including 4 pts (5.5%) whose death was considered therapy related. Conclusions: Concurrent PE/XRT followed by consolidation D is associated with a high rate of grade 3/4 toxicities and hospitalizations, including treatment-related deaths. Updated toxicity data will be presented at the ASCO meeting. Whether consolidation D confers a survival advantage is not yet known. [Table: see text]

Induction chemotherapy followed by concurrent chemoradiotherapy (CCRT) versus CCRT alone for unresectable stage III non-small cell lung cancer (NSCLC): Randomized phase III trial

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7528-7528 ◽  
Author(s):  
S. Kim ◽  
M. Kim ◽  
E. Choi ◽  
H. Sohn ◽  
D. Lee ◽  
...  
Keyword(s):  
Induction Chemotherapy ◽  
Concurrent Chemoradiotherapy ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Stage Iii ◽  
Phase Iii Trial ◽  
Free Survival ◽  
Unresectable Stage ◽  
Stage Iii Nsclc ◽  
Grade 3

7528 Background: We conducted a prospective randomized phase III trial comparing induction chemotherapy followed by concurrent chemoradiotherapy (CCRT) versus immediate CCRT to evaluate whether the addition of induction chemotherapy would result in improved survival. Methods: Patients with unresectable stage III NSCLC, ECOG PS 0–1, and weight loss up to 10% were eligible. They were randomized to receive either induction chemotherapy followed by CCRT (arm A) or immediate CCRT (arm B) after stratification for stage (T4N0–2, T1–3N3, T4N3, and stage IIIA), histology (squamous vs non-squamous), and SCLN positivity. Induction chemotherapy consisted of two cycles of gemcitabine (1,000 mg/m2 D1, D8) and cisplatin (70 mg/m2 D1) q 21days. Chemotherapy during CCRT consisted of 6 cycles of weekly paclitaxel (50 mg/m2) and cisplatin (20 mg/m2). Radiation therapy performed with hypofractionated scheme (2.2 Gy/fraction, once a day) and total dose was 66 Gy. Irradiated volume encompassed gross tumor plus 1.0 cm margin. Results: Between March 2003 and June 2006, 134 patients were enrolled. 92% of patients were male and 60% were age 60 or older. Objective tumor response was obtained in 38% after induction chemotherapy. Response rates after completion of CCRT were 72% (95% CI, 61%–83%) on arm A and 79% (95% CI, 69%–89%) on arm B. Grade 3/4 toxicities during induction chemotherapy consisted mainly of neutropenia (11%/3%). During CCRT, grade 3/4 neutropenia was noted in 8%/5% (arm A) versus in 8%/0% (arm B), grade 3 anemia was 8% vs 0%, grade 3 thrombocytopenia 5% vs 0%, and grade 3 esophagitis 16% vs 16%. At median follow-up of 28 months, median survival was 12.6 months (95% CI, 8.6–16.7 months) on arm A versus 18.2 months (95% CI, 11.7–24.8 months) on arm B (P=0.18). Two year survival estimates was 25% (15%–35%) and 43% (31%–55%), respectively. Median progression free survival was 7.5 months (95% CI, 5.6–9.4 months) on arm A and 11.6 months (95% CI, 9.6–13.6 months) on arm B (P=0.04). Conclusions: The addition of induction chemotherapy to CCRT failed to increase the survival of unresectable stage III NSCLC over immediate CCRT. Moreover, the progression free survival was inferior to immediate CCRT. No significant financial relationships to disclose.

The value of combined modality therapy in elderly patients with stage III non-small cell lung cancer (NSCLC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 19503-19503 ◽  
Author(s):  
S. E. Schild ◽  
S. J. Mandrekar ◽  
A. Jatoi ◽  
W. L. McGinnis ◽  
P. J. Stella ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Combined Modality Therapy ◽  
Survival Rates ◽  
Concurrent Chemotherapy ◽  
Phase Iii ◽  
Stage Iii ◽  
Combined Modality ◽  
Phase Iii Trials ◽  
Stage Iii Nsclc ◽  
Grade 3

19503 Background: This study was performed to assess the value of combined modality therapy in elderly patients by comparing the differences in outcome of those who received radiotherapy (RT) alone or RT plus chemotherapy for stage III NSCLC. Methods: North Central Cancer Treatment Group (NCCTG) performed 2 recent phase III trials for stage III NSCLC. The first trial, 90–24–51, included 3 arms: once-daily radiotherapy (QDRT) alone, twice daily RT (BIDRT) alone, and concurrent chemotherapy plus BIDRT. The second trial, 94–24- 52 included 2 arms and compared concurrent chemotherapy with either QDRT or BIDRT. The chemotherapy arms of both trials included etoposide and cisplatin administered concurrently with RT. Only the patients ≥65 years of age (elderly) who participated in these trials were included in this analysis. Results: Of the 166 elderly patients included in this analysis, 37 received RT alone and 129 received concurrent chemotherapy plus RT. The median and 5-year survival rates were 10.5 months and 5.4% for the RT alone group compared to 13.7 months and 14.7% for the RT plus chemotherapy group (log-rank p=0.05). Patients who received RT plus chemotherapy experienced significantly greater severe (grade ≥3) toxicity than those who received RT alone (89.9% versus 32.4%, p < 0.01). Conclusions: Elderly patients who participated in these trials appear to gain a survival advantage from RT and chemotherapy compared to RT alone. As is the case with younger patients, this benefit comes at the cost of additional toxicity. No significant financial relationships to disclose.

Consolidation nivolumab/ipilimumab versus nivolumab following concurrent chemoradiation in patients with unresectable stage III NSCLC: A planned interim safety analysis from the BTCRC LUN 16-081 trial.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9010-9010 ◽  
Author(s):  
Melissa Yan ◽  
Greg Andrew Durm ◽  
Hirva Mamdani ◽  
Vinicius Ernani ◽  
Salma K. Jabbour ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cycle Length ◽  
Stage Iv ◽  
Safety Analysis ◽  
Median Number ◽  
Stage Iii ◽  
Stage Iiia ◽  
Unresectable Stage ◽  
Stage Iii Nsclc ◽  
Grade 3

9010 Background: Consolidation PD-1/PD-L1 inhibition after chemoradiation (CRT) for unresectable stage III NSCLC improves overall survival. In stage IV NSCLC, the combination of nivolumab/ipilimumab improved overall survival compared to chemotherapy in patients with PD-L1 > 1% and performed favorably in patients with PD-L1 < 1%. The safety of consolidation nivolumab/ipilimumab after CRT has not been previously assessed. Methods: In this randomized, multi-center, phase II study, a total of 105 planned pts with unresectable stage IIIA/IIIB NSCLC will receive chemoradiation, then randomize 1:1 to either nivolumab 480mg IV q4 wks (Arm A) or nivolumab 3mg/kg IV q2 wks + ipilimumab 1mg/kg IV q6 wks (Arm B), for up to 24 wks. In this planned interim analysis, the safety of the first 50 patients, with 25 patients treated on each arm, is assessed. Results: From 9/2017 to 6/2019, the first 50 patients were accrued and analyzed for this planned safety analysis. Baseline characteristics for Arm A/B: median age 64/62, stage IIIA 17/16, stage IIIB 8/9, non-squamous 14/13, squamous 11/12. The median number of cycles completed in Arm A was 6 (range 1-6, cycle length q4 wks) and in Arm B was 4 (range 1-4, cycle length q6 wks). The rate of treatment-related adverse events leading to discontinuation of therapy was 16% in Arm A and 40% in Arm B. The percentage of patients with any > grade 3 adverse event (AE) was 32% in Arm A and 44% in Arm B. With respect to immune-related AE (irAEs), the percentage of patients with any ≥grade 2 was 44% in Arm A and 60% in Arm B; any ≥ grade 3 irAEs was 16% in Arm A and 32% in Arm B. The incidence of > grade 2 pneumonitis was 16% in Arm A and 36% in Arm B. The percentage of patients with > grade 3 pneumonitis was 4% in Arm A and 20% in Arm B. No treatment-related deaths were reported on either arm. Conclusions: In the post chemoradiation setting, the incidence of > grade 3 toxicity was greater in the consolidative nivolumab/ipilimumab arm, which resulted in a higher rate of treatment discontinuation than nivolumab alone. The Data and Safety Monitoring Board recommended continued enrollment without modification to the trial and the study currently remains open to accrual (66 of 105 patients have been enrolled as of 1/17/2020). Clinical trial information: NCT03285321.

scholarly journals Randomized Phase III Study of Thoracic Radiation in Combination With Paclitaxel and Carboplatin With or Without Thalidomide in Patients With Stage III Non–Small-Cell Lung Cancer: The ECOG 3598 Study

2012 ◽  
Vol 30 (6) ◽  
pp. 616-622 ◽  
Author(s):  
Tien Hoang ◽  
Suzanne E. Dahlberg ◽  
Joan H. Schiller ◽  
Minesh P. Mehta ◽  
Thomas J. Fitzgerald ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Locally Advanced ◽  
Small Cell ◽  
Phase Iii ◽  
Stage Iii ◽  
Small Cell Lung ◽  
Thoracic Radiation ◽  
Grade 3

Purpose The primary objective of this study was to compare the survival of patients with unresectable stage III non–small-cell lung cancer (NSCLC) treated with combined chemoradiotherapy with or without thalidomide. Patients and Methods Patients were randomly assigned to the control arm (PC) involving two cycles of induction paclitaxel 225 mg/m2 and carboplatin area under the curve (AUC) 6 followed by 60 Gy thoracic radiation administered concurrently with weekly paclitaxel 45 mg/m2 and carboplatin AUC 2, or to the experimental arm (TPC), receiving the same treatment in combination with thalidomide at a starting dose of 200 mg daily. The protocol allowed an increase in thalidomide dose up to 1,000 mg daily based on patient tolerability. Results A total of 546 patients were eligible, including 275 in the PC arm and 271 in the TPC arm. Median overall survival, progression-free survival, and overall response rate were 15.3 months, 7.4 months, and 35.0%, respectively, for patients in the PC arm, in comparison with 16.0 months (P = .99), 7.8 months (P = .96), and 38.2% (P = .47), respectively, for patients in the TPC arm. Overall, there was higher incidence of grade 3 toxicities in patients treated with thalidomide. Several grade 3 or higher events were observed more often in the TPC arm, including thromboembolism, fatigue, depressed consciousness, dizziness, sensory neuropathy, tremor, constipation, dyspnea, hypoxia, hypokalemia, rash, and edema. Low-dose aspirin did not reduce the thromboembolic rate. Conclusion The addition of thalidomide to chemoradiotherapy increased toxicities but did not improve survival in patients with locally advanced NSCLC.

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