Induction (ICT) or consolidation chemotherapy (CT) with cisplatin (C) and paclitaxel (P) plus concurrent chemo-radiation (CT/TRT) with cisplatin and vinorelbine (V) for unresectable non-small cell lung cancer (NSCLC) patients (pts): Randomized phase II trial GFPC-GLOT-IFCT 02–01

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7048-7048 ◽  
Author(s):  
P. Fournel ◽  
A. Vergnenégre ◽  
G. Robinet ◽  
H. Léna ◽  
R. Gervais ◽  
...  
Keyword(s):  
Response Rate ◽  
Superior Vena ◽  
Objective Response ◽  
Vena Cava ◽  
Primary Objective ◽  
Stage Iii ◽  
Massive Hemoptysis ◽  
Unresectable Stage ◽  
End Of Treatment ◽  
Stage Iii Nsclc

7048 Background: Concurrent CT/TRT is the standard treatment for unresectable stage III NSCLC, but the optimal sequencing of TRT and CT is not well defined.Consolidation CT with taxane seems to be a good approach (SWOG 95–04). Methods: Unresectable stage III NSCLC pts (weight loss < 10%, ECOG PS 0–1, no supraclavicular lymph node or superior vena cava syndrome) were eligible. in Arm A, pts received 2 cycles of C 80 mg/m2 and P 200 mg/m2 followed by a concurrent CT/TRT including TRT as 66 Gy in 33 fractions and C 80 mg/m2 d1,29 and 57 and V d1,8,29,36,57 and 64. In Arm B, the same CT/TRT began on d1 followed by 2 cycles of C and P. The primary objective was response rate at the end of treatment, assessed by RECIST criteria. 132 pts were needed. Results: From 05/2002 to 03/2005, 133 pts were included by 35 centers. 5 pts were ineligible. Both groups were well-matched for baseline characteristics. 30 pts were stage IIIAN2 and 98 stage IIIB. Toxicities (106 pts analyzable) grade 3–4 by CTC and RTOG criteria (Arm A/Arm B) were: neutropenia 36%/41%, infection 11%/15%, esophagitis 6%/13%, pneumonitis 0%/1%. 5 toxic deaths were observed (2 sepsis, 1 massive hemoptysis, 1 post-irradiation pneumonitis, 1 esophageal fistula). In Arm A, objective response rate was 36% after ICT. At the end of treatment, response rate (Arm A/Arm B) was in intent to treat: progression 19%/19%, stable-disease 6%/11%, objective response 55%/48%. 13 pts were not evaluable for response in Arm A and 14 in Arm B [ table ]. Conclusions: Toxicities and response rates are similar in both arms, but ICT followed by CT/TRT appears to provide a better therapeutic outcome. [Table: see text] No significant financial relationships to disclose.

Thoracic radiotherapy PLUS durvalumab in elderly and/or frail NSCLC stage III patients unfit for chemotherapy: Employing optimized (hypofractionated) radiotherapy to foster durvalumab efficacy—The TRADE-hypo trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS8585-TPS8585
Author(s):  
Farastuk Bozorgmehr ◽  
Jessica Juergens ◽  
Michaela Hammer-Hellmig ◽  
Christian Meyer Zum Bueschenfelde ◽  
Johannes Classen ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Objective Response ◽  
Stage Iii ◽  
Hypofractionated Radiotherapy ◽  
Poor Performance Status ◽  
Thoracic Radiotherapy ◽  
Therapy Algorithm ◽  
Safety And Efficacy ◽  
Unresectable Stage ◽  
Stage Iii Nsclc

TPS8585 Background: Non-small cell lung cancer (NSCLC) is the most common cause of cancer death worldwide highlighting the importance of improving current therapeutic options. In particular, elderly and frail patients are not only underrepresented in clinical trials, but also frequently do not receive standard treatment regimens due to comorbidities. For example, patients with unresectable stage III NSCLC who are unfit for chemotherapy (CHT) do not benefit from the recent seminal therapy algorithm change for this disease, i.e. consolidation therapy with the immune checkpoint inhibitor (ICI) durvalumab after combined radiochemotherapy (RChT). Instead, these patients are treated with radiotherapy only, raising the serious concern of undertreatment. This issue is addressed by the TRADE-hypo clinical trial that investigates a novel therapy option for NSCLC stage III patients not capable of receiving CHT. To this end, thoracic radiotherapy (TRT) is administered together with durvalumab, employing the synergism created by the combination of restoring anti-tumor immune response by the ICI with the induction of immunogenicity by irradiation. The latter effect has been suggested to be further boosted by hypofractionated radiotherapy, which could also be more practicable for the patient. Taken these considerations into account, the TRADE-hypo trial addresses safety and efficacy of durvalumab therapy combined with either conventional or hypofractionated TRT. Methods: The TRADE-hypo trial is a prospective, randomized, open-label, multicentric phase II trial. Eligible patients are diagnosed with unresectable stage III NSCLC and not capable of receiving sequential RChT due to high vulnerability as reflected by a poor performance status (ECOG 2 or ECOG1 and CCI≥ 1) and/or high age (≥ 70)]. Two treatment groups are evaluated: Both receive durvalumab (1,5000 mg, Q4W) for up to 12 months. In the CON-group this is combined with conventionally fractionated TRT (30 x 2 Gy), while in the HYPO-group patients are treated with hypofractionated TRT (20 x 2.75 Gy). In the HYPO-arm, a safety stop-and-go lead-in phase precedes full enrollment. Here, patients are closely monitored with regard to toxicity (i.e., pneumonitis grade ≥ 3 within 8 weeks after TRT) in small cohorts of 6. The primary objective of the trial is safety and tolerability. As a primary efficacy endpoint, the objective response rate after 3 months will be evaluated. Further endpoints are additional parameters of safety and efficacy, as well as the comprehensive collection of biomaterials to be analyzed regarding treatment-induced changes and potential novel biomarkers. As of February 10, 2021, 9 patients of planned 88 patients have been enrolled in the TRADE-hypo trial. Clinical trial information: NCT04351256.

Phase II study of TS-1 (S) plus cisplatin (P) with concurrent thoracic radiotherapy for unresectable stage III non-small cell lung cancer (NSCLC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18070-18070
Author(s):  
F. Ohyanagi ◽  
N. Yamamoto ◽  
A. Horiike ◽  
T. Horai ◽  
K. Gomi ◽  
...  
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Study ◽  
Performance Status ◽  
Progression Free Survival ◽  
Stage Iii ◽  
Fourth Generation ◽  
Unresectable Stage ◽  
Stage Iii Nsclc ◽  
Grade 3

18070 Background: Although combined chemoradiotherapy is the standard of care in stage III NSCLC, the optimal chemotherapy regimen is not established. S-1, a fourth-generation oral fluoropyrimidine is an active new agent for NSCLC and the combination with cisplatin has a favorable toxicity profile. The objective of this study was to evaluate feasibility and efficacy of S plus P with concurrent radiation for unresectable stage III NSCLC. Methods: Patients with histologically or cytologically confirmed NSCLC, 20 to 75 years in age, performance status 0–1, with no prior chemotherapy were eligible for the study. Patients were treated with P (60 mg/m2 on day 1) and S (orally at 40 mg/m2/dose bid (80 mg/m2/d), on days 1 to 14) repeated every 3–4 weeks for 4 cycles and TRT (60 Gy/30 fr over 6 weeks starting on day 2). The primary endpoint was the response rate (RR), and planned sample size for this phase II study was 28 patients (Simon’s two-stage minimax design, P0=70%, P1=90%, a =0.1, β = 0.1). Results: Of 28 patients enrolled between August 2005 and October 2006, 28 were evaluable. There were 24 males and 4 females, median age of 63 (range 40–74) and 11 IIIA and 17 IIIB. Chemoradiotherapy was well tolerated; 2 cycles of SP and 60 Gy of TRT were administered in all patients and 24 (86%) patients received 4 cycles of SP. During concurrent chemoradiotherapy, grade 3 toxicities were neutropenia (8 pts), leukopenia (6 pts), fatigue (6 pts), anorexia (5 pts), febrile neutropenia (4 pts) and, esophagitis (4 pts). Only one grade 4 leukopenia were observed. During consolidation therapy, grade 3–4 neutropenia, anemia, esophagitis, and pneumonitis were developed in 4, 1, 1 and 2 patients, respectively. No toxic deaths have occurred. Overall RR was 85.7% (95% CI: 79.1- 98.7%) with 4 SDs and 24 PRs. The median progression-free survival and median survival is not mature enough to estimate as only 4 progression and no deaths have occurred. Conclusions: This chemoradiotherapy regimen produced promising response rate in patients with stage III NSCLC and it seems to be well-tolerated. No significant financial relationships to disclose.

Oral vinorelbine and cisplatin with concomitant radiotherapy in stage III non-small cell lung cancer (NSCLC): COVeRT study.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e17544-e17544
Author(s):  
Nimit Singhal ◽  
Kenneth B. Pittman ◽  
Christos Stelios Karapetis ◽  
Sonya Stephens ◽  
Martin Borg
Keyword(s):  
Response Rate ◽  
Single Agent ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Stage Iii ◽  
Significant Activity ◽  
Serious Adverse Events ◽  
Oral Vinorelbine ◽  
Stage Iii Nsclc ◽  
Radical Radiation

e17544 Background: Chemoradiation is standard of care for the treatment of stage III NSCLC. Vinorelbine has been widely used for the treatment in NSCLC and it has been established, either as single agent or in combination with platinum, as one of the standard reference treatments. Oral vinorelbine is a new formulation which has achieved comparable results to the IV vinorelbine. The present trial is evaluating combination of oral vinorelbine, cisplatin with radical radiation for management of stage III NSCLC. Methods: Patients with diagnosis of stage III NSCLC with PS 0-1 and adequate cardio-respiratory function. Primary objective: progression-free survival. Secondary objectives: response rate, overall survival and safety profile. Treatment - chemotherapy (2 cycles q 21 days): vinorelbine oral 50 mg/m2 d1, d8. Cisplatin 100 mg/m2/ cycle (given as either 20mg/m2 D1-5 or 50mg/m2 D1 and D8) - radiotherapy: 60 Gy in 30 fractions at 2 Gy/ fraction to the isocentre, treating all fields daily, 5 days a week over 6 weeks using 10 MV photons and 3-D CRT. Results: Since May 2008, 33 patients have been enrolled with 31 patients having completed treatment so far. The data is presented for these 25 patients. 16 were male with age ranging from 50-89. The median age was 66. 13 patients had stage IIIa. There were 11 squamous cell carcinoma and 10 adenocarcinoma. The side effects were generally mild and included Gr I, II nausea, constipation and esophagitis. Serious adverse events requiring admission included dehydration, fever with grade I neutropenia, atrial fibrillation and UTI in one patient each. One patient had tracheo-esophageal fistula resulting in death within 30 days of completing chemoRT and was attributed to treatment. The confirmed radiological response assessment is available for 22 patients with 1 CR, 13 PR, 7 SD and 1 PD giving a total response rate of 64%. Conclusions: Two cycles of chemotherapy with oral vinorelbine and cisplatin plus radical radiation appears to be well tolerated with significant activity in stage III NSCLC.

PACIFIC-2: Phase 3 study of concurrent durvalumab and platinum-based chemoradiotherapy in patients with unresectable, stage III NSCLC.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS8573-TPS8573 ◽  
Author(s):  
Jeffrey D. Bradley ◽  
Makoto Nishio ◽  
Isamu Okamoto ◽  
Michael David Newton ◽  
Leonardo Trani ◽  
...  
Keyword(s):  
Performance Status ◽  
Objective Response ◽  
Additional Benefit ◽  
Stage Iii ◽  
Phase 3 ◽  
Ecog Performance Status ◽  
Double Blind ◽  
Unresectable Stage ◽  
Stage Iii Nsclc ◽  
To Receive

TPS8573 Background: Durvalumab, a selective, high-affinity, engineered human IgG1 mAb that blocks PD-L1 binding to PD-1 and CD80, is approved in the US, Japan and several other countries, for the treatment of patients (pts) with unresectable, stage III non-small cell lung cancer (NSCLC) whose disease has not progressed following concurrent chemoradiotherapy (cCRT). These approvals were based on results from the phase 3 PACIFIC study, in which durvalumab was given 1–42 days after completion of definitive cCRT and significantly improved progression-free survival (PFS) vs placebo (median 16.8 vs 5.6 months; HR 0.52, 95% CI 0.42– 0.65; p<0.001) and overall survival (OS) vs placebo (stratified HR 0.68; 99.73% CI 0.47–0.997; p=0.0025). Increasing evidence suggests additional benefit when anti-PD-1/PD-L1 therapies are administered alongside cCRT. The PACIFIC 2 study therefore aims to assess whether durvalumab plus cCRT provides additional benefit, in terms of PFS and objective response rate (ORR), compared with cCRT alone. Methods: PACIFIC 2 is a phase 3, randomized, double-blind, placebo-controlled, multicenter, international study. Approximately 300 pts with unresectable stage III NSCLC will be randomized (2:1) to receive either durvalumab (intravenous 1500 mg) every 4 weeks (q4w) + cCRT, or placebo q4w + cCRT. Eligible pts must have histologically or cytologically confirmed stage III disease; ECOG performance status 0 or 1; and life expectancy >12 weeks at randomization. Pts who discontinue treatment will be followed for safety and OS. Primary endpoints are PFS and ORR (RECIST v1.1) assessed via blinded independent central review. Secondary endpoints include OS; OS at month 24; complete response (CR) rate; duration of response; disease control rate; time to death/distant metastases; time from randomization to second progression; safety; and symptoms, functioning and global health status. Pts with a CR, partial response or stable disease will continue to receive durvalumab or placebo until clinical or RECIST v1.1-defined disease progression, or until another discontinuation criterion is met. Study enrollment began in March 2018 and recruitment is ongoing. Clinical trial information: NCT03519971.

Gemstone-301: A phase III clinical trial of CS1001 as consolidation therapy in subjects with locally advanced/unresectable (stage III) non-small cell lung cancer (NSCLC) who have not progressed after prior concurrent/sequential chemoradiotherapy (CRT).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS8572-TPS8572
Author(s):  
Yi-Long Wu ◽  
Ming Chen ◽  
Qing Zhou ◽  
Hao Li ◽  
Wenyi Sun ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Objective Response ◽  
Locally Advanced ◽  
Phase Iii ◽  
Stage Iii ◽  
Transgenic Rat ◽  
Consolidation Therapy ◽  
Double Blind ◽  
Unresectable Stage ◽  
Stage Iii Nsclc

TPS8572 Background: In China, the standard of care for patients with unresectable Stage III NSCLC is platinum-based doublet chemotherapy given concurrently or sequentially with radiotherapy. However, the median progression-free survival (PFS) of those patients is poor (approximately 8-10 months) and 5-year overall survival (OS) rate is only 15%. Recently, treatment with durvalumab resulted in significantly longer PFS and OS than placebo for patients with locally advanced/unresectable NSCLC whose disease did not progress after definitive concurrent chemoradiotherapy (cCRT) in PACIFC trial. CS1001 is the first full-length, fully human programmed death ligand-1 (PD-L1) targeted immunoglobin G4 (IgG4, s228p) monoclonal antibody (mAb) developed by the OMT transgenic rat platform. The Phase Ia/Ib study (GEMSTONE-101, NCT03312842) demonstrated that CS1001 was well tolerated and had promising anti-tumor activities across a range of tumors including NSCLC. GEMSTONE-301 is a randomized, double-blind, Phase III study to compare the efficacy and safety of CS1001 versus placebo as consolidation therapy in Stage III unresectable NSCLC patients. This is the first Phase III trial on an anti-PD-(L)1 mAb initiated in China for this indication. Methods: In this trial, eligible patients with locally advanced/unresectable (Stage III) NSCLC who have not progressed after prior concurrent/sequential CRT are 2:1 randomized to receive CS1001 1200 mg, every 3 weeks or placebo, every 3 weeks. Stratification factors for randomization include ECOG status (0 versus 1), chemoradiotherapy (concurrent versus sequential) and total radiotherapy dose ( < 60 Gy versus ≥ 60 Gy). Study treatment will be given for up to 24 months or until disease progression, intolerable toxicity, consent withdrawal, or discontinuation for other reason. Tumor assessments will be performed every 9 weeks in the first year and every 12 weeks thereafter by RECIST v1.1. AEs will be monitored throughout the study and graded according to NCI-CTCAE v4.03. Primary endpoint is PFS evaluated by investigators according to RECIST v1.1. Secondary endpoints are PFS evaluated by Blinded Independent Center Review (BICR), objective response rate, OS, time to death/distant metastasis (TTDM), safety and pharmacokinetics (PK) profile. Enrollment is ongoing across sites in China and will continue until 402 patients are randomized. Clinical trial information: NCT03728556.

Retrospective review of stage III non-small cell lung cancer (NSCLC) patients treated with carboplatin/paclitaxel plus radiotherapy followed by docetaxel

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18123-18123
Author(s):  
M. R. Patel ◽  
M. Weidner ◽  
J. W. Lynch ◽  
E. Walden ◽  
T. J. George
Keyword(s):  
Response Rate ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Stage Iii ◽  
Consolidation Therapy ◽  
Free Survival ◽  
Phase Ii Studies ◽  
Unresectable Stage ◽  
Stage Iii Nsclc

18123 Background: Concurrent chemoradiotherapy is standard of care for unresectable patients and the most widely cited trials include the locally advanced multi-modality protocol (LAMP) study, SWOG S9019 and S9504. Our institutional approach represents a merger between the protocols utilized in two of these phase II studies: chemoradiotherapy from the LAMP study and consolidation therapy from SWOG S9504. Methods: We identified all stage III patients treated at the NF/SG VHS from Jan 2001 to Dec 2005. Eligible patients who had unresectable stage III NSCLC were included in the analysis. We treated 34 patients with weekly paclitaxel 45 mg/m2 plus carboplatin AUC 2 and concurrent TRT 63.0 Gy over 7 weeks. Four weeks after the completion of chemoradiotherapy, docetaxel 75 mg/m2 was given every 3 weeks for 21 days for 3 cycles as consolidation. Our primary endpoints were overall and progression free survival. The secondary endpoints were response rate and toxicity. Results: With a median age of 65 years and follow-up time of 25.9 months, median overall survival was 13.7 mos. Median progression free survival was 9.8 mos. The overall response rate was 68% including 5 CRs (15%). The most common grade 3/4 toxicities included pneumonitis (21%), esophagitis (21%), neutropenia (21%) [febrile neutropenia (9%)], neuropathy (18%), anemia (15%) and hypersensitivity to paclitaxel (9%). 62% of patients were able to complete the planned treatment. There were no treatment related deaths. At the time of this analysis, 9 patients were alive (26%) including 7 without progression (21%). Conclusions: Chemoradiotherapy with weekly carboplatin and paclitaxel followed by consolidation therapy with docetaxel is associated with comparable outcomes to other combined modality regimens. Given the advanced age and co-morbidities of our population, this regimen was generally well tolerated with the expected toxicities and can be considered as an option in the treatment of patients with unresectable stage III NSCLC. No significant financial relationships to disclose.

Five-year survival outcomes with durvalumab after chemoradiotherapy in unresectable stage III NSCLC: An update from the PACIFIC trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 8511-8511
Author(s):  
David R. Spigel ◽  
Corinne Faivre-Finn ◽  
Jhanelle Elaine Gray ◽  
David Vicente ◽  
David Planchard ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Standard Of Care ◽  
Phase Iii ◽  
Stage Iii ◽  
Smoking History ◽  
Kaplan Meier ◽  
Unresectable Stage ◽  
The Pacific ◽  
Patient Reported ◽  
Stage Iii Nsclc

8511 Background: In the placebo-controlled Phase III PACIFIC trial of patients with unresectable Stage III NSCLC whose disease had not progressed after platinum-based concurrent chemoradiotherapy (cCRT), durvalumab improved overall survival (OS) (stratified hazard ratio [HR] 0.68; 95% confidence interval [CI] 0.53–0.87; p=0.0025; data cutoff [DCO] Mar 22, 2018) and progression-free survival (PFS) (stratified HR 0.52, 95% CI 0.42–0.65; p<0.0001; DCO Feb 13, 2017) based on the DCOs used for the primary analyses, and the degree of benefit remained consistent in subsequent updates. Durvalumab was associated with a manageable safety profile, and did not detrimentally affect patient-reported outcomes, compared with placebo. These findings established consolidation durvalumab after CRT (the ‘PACIFIC regimen’) as the standard of care in this setting. We report updated, exploratory analyses of OS and PFS, assessed approximately 5 years after the last patient was randomized. Methods: Patients with WHO PS 0/1 (and any tumor PD-L1 status) whose disease did not progress after cCRT (≥2 overlapping cycles) were randomized (2:1) 1–42 days following cCRT (total prescription radiotherapy dose typically 60–66 Gy in 30–33 fractions) to receive 12 months’ durvalumab (10 mg/kg IV every 2 weeks) or placebo, stratified by age (<65 vs ≥65 years), sex, and smoking history (current/former smoker vs never smoked). The primary endpoints were OS and PFS (blinded independent central review; RECIST v1.1) in the intent-to-treat (ITT) population. HRs and 95% CIs were estimated using stratified log-rank tests in the ITT population. Medians and OS/PFS rates at 60 months were estimated with the Kaplan–Meier method. Results: Overall, 709/713 randomized patients received treatment in either the durvalumab (n/N=473/476) or placebo (n/N=236/237) arms. The last patient had completed study treatment in May 2017. As of Jan 11, 2021 (median follow-up duration of 34.2 months in all patients; range, 0.2–74.7 months), updated OS (stratified HR 0.72, 95% CI 0.59–0.89; median 47.5 vs 29.1 months) and PFS (stratified HR 0.55, 95% CI 0.45–0.68; median 16.9 vs 5.6 months) remained consistent with the results from the primary analyses. The 60-month OS rates were 42.9% and 33.4% with durvalumab and placebo, respectively, and 60-month PFS rates were 33.1% and 19.0%, respectively. Updated treatment effect estimates for patient subgroups will be presented. Conclusions: These updated survival analyses, based on 5-year data from PACIFIC, demonstrate robust and sustained OS plus durable PFS benefit with the PACIFIC regimen. An estimated 42.9% of patients randomized to durvalumab remain alive at 5 years and approximately a third remain both alive and free of disease progression. Clinical trial information: NCT02125461.

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