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.

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.

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.

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.

scholarly journals DUART: durvalumab after radiotherapy in patients with unresectable, stage III NSCLC who are ineligible for chemotherapy

2021 ◽  
Author(s):  
Andrea R Filippi ◽  
Rafał Dziadziuszko ◽  
Maria Rosario García Campelo ◽  
Jean-Baptiste Paoli ◽  
William Sawyer ◽  
...  
Keyword(s):  
Performance Status ◽  
Poor Performance ◽  
Standard Of Care ◽  
Stage Iii ◽  
Poor Performance Status ◽  
Open Label ◽  
Unresectable Stage ◽  
The Pacific ◽  
Radiotherapy Alone ◽  
Stage Iii Nsclc

Consolidation durvalumab is standard of care in patients with unresectable, stage III non-small-cell lung cancer (NSCLC) without disease progression following chemoradiotherapy (the ‘PACIFIC regimen’). However, many patients with poor performance status, older age or comorbidities may be ineligible for chemotherapy due to expected high toxicity. These patients typically receive radiotherapy alone, with poor survival outcomes. Based on the PACIFIC trial data, and the strong biological rationale for combining radiotherapy with anti-programmed cell death ligand-1 therapy, durvalumab following radiotherapy could provide additional survival benefit versus radiotherapy alone. Here, we describe the DUART trial, a Phase II, open-label, single-arm study assessing the safety and tolerability of durvalumab following radiotherapy in patients with unresectable, stage III NSCLC who are ineligible for chemotherapy (ClinicalTrials.gov Identifier: NCT04249362 ).

Randomized phase II trial of S-1 plus cisplatin or docetaxel plus cisplatin with concurrent thoracic radiotherapy for inoperable stage III non-small cell lung cancer (TORG1018).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 8534-8534
Author(s):  
Kaoru Kubota ◽  
Tsuneo Shimokawa ◽  
Kazuhiko Yamada ◽  
Hiroshi Tanaka ◽  
Kazuma Kishi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Objective Response ◽  
Dose Intensity ◽  
Small Cell ◽  
Stage Iii ◽  
Thoracic Radiotherapy ◽  
Small Cell Lung ◽  
Stage Iii Nsclc

8534 Background: Concurrent chemoradiotherapy (CCRT) is standard of care in patients with inoperable stage III non-small cell lung cancer (NSCLC), however the best chemotherapy regimen has not been identified. The study was conducted to evaluate cisplatin plus S-1 (SP) or cisplatin plus docetaxel (DP) both with concurrent thoracic radiotherapy in patients with inoperable stage III NSCLC. Methods: Patients with inoperable stage III NSCLC were randomized to SP (S-1 40 mg/m2 twice a day on days 1-14 and 29-42 plus cisplatin 60 mg/m2 on days 1 and 29) or DP (docetaxel 50 mg/m2 and cisplatin 80 mg/m2 on days 1 and 29), stratified by institution, gender, histology, and stage. In both arms, concurrent radiotherapy began on day 1 (60 Gy/30 fr). After CCRT, patients in each group received two additional cycles of the consolidation chemotherapy. Primary endpoint was 2-year overall survival (OS), and secondary endpoints were OS, progression-free survival (PFS), toxicity profile, dose intensity and objective response rate (ORR). Results: From May 2011 to August 2014, 110 patients were enrolled from 19 institutions. Four patients (one in SP and 3 in DP) were ineligible, and 106 patients (53 in each arm) were evaluable for efficacy and safety. Patient characteristics were: male/female 83/23; median age 65 (range 42-74); performance status 0/1 59/47; IIIA/IIIB 59/47. With a median follow-up of 39.3 months, 2-year survival and median OS were 79% (95% CI: 66-88%) and 55.2 months in the SP arm and 69% (95% CI: 55-80%) and 50.8 months in the DP arm, respectively. ORR and median PFS in SP arm were 71.7% and 11.6 months, and ones in the DP arm were 67.9% and 19.9 months. Grade 3/4 leukopenia (62.3/34.0%) and neutropenia (56.6/28.3%) were significantly more frequent in DP arm than SP arm. Incidences of non-hematological toxicities including febrile neutropenia, anorexia, nausea, diarrhea, radiation pneumonitis and esophagitis tended to be higher in DP arm. No treatment-related death occurred. Conclusions: The 2-year OS favored for SP arm with less toxicity. We choose SP with concurrent thoracic radiotherapy as a future reference regimen. Clinical trial information: UMIN000005993.

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