OA01.07 Updated Results of a Phase II Trial of Concurrent Chemoradiation with Consolidation Pembrolizumab in Patients with Unresectable Stage III NSCLC

7188 Background: Concurrent CRT improves outcomes for pts with unresectable stage III NSCLC compared with radiation (RT) alone. The EGFR inhibitor G benefits select pts with advanced NSCLC. This multicenter community phase II trial examined the role of CRT followed by G for pts with unresectable stage III NSCLC. Methods: Theprimary endpoint was 2-year overall survival (OS) in pts with unresectable stage IIIA/B NSCLC (effusions, N3 mediastinal nodes >4 cm excluded) treated with CRT followed by G. Induction(I) treatment (tx): docetaxel (D) 40 mg/m2 IV and gemcitabine 800 mg/m2 IV D1, 8 Q 21D × 3 cycles. Pts without progressive disease (PD) began: D 20 mg/m2 IV and carboplatin (C) AUC = 1.5 IV weekly × 6 and RT 61.2 Gy, 1.8-Gy M-F weekly × 7 (starting 1 week prior to D/C). If no PD, pts received G 250 mg PO daily × 2 years or until PD. Eligibility:measurable disease, ECOG PS 0–1, informed consent. Intent to treat analysis. Results: One-hundred three pts were enrolled from 7/03 to 4/05. Baseline features: medianage 60 years (37–79); male/female 54%/46%; ECOG PS 0/1:26%/74%; adenocarcinoma (26%), squamous (32%), large cell (28%), mixed/not specified (14%); IIIA/B (46%/54%). Grade 3/4 toxicities were limited to ≤ 8% except for neutropenia (17%, during I) - with notx-related deaths. Complete/partial responses after I were seen in 1 pt/34 pts, respectively, for an overall response rate (RR) of 34% (95% CI 26%-44%). Forty-two pts (41%) had stable disease (SD) and 12% had PD (9 pts were unevaluable.) Seventy-four pts (72%) received D/C/RT which resulted in an overall RR of 44% (95% CI 35%-54%). Fifteen percent had SD. Fifty-six pts (54%) received G for a median of 28 weeks (1–107). Median PFS and OS are 9.9 and 15 months, respectively. After a median follow-up of 19 months, actuarial 1- and 2-year progression-free survival (PFS) is 41% and 12%, respectively. 1- and 2-year OS rates are 64% and 21%, respectively. Subset analyses by smoking, gender, histology, and stage are in progress. Conclusions: Maintenance G following CRT in unresectable NSCLC does not appear to improve survival. It is possible that further analysis may suggest a role for G in selected pts. [Table: see text]

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A phase II trial of consolidation nivolumab or nivolumab plus ipilimumab following concurrent chemoradiation in unresectable stage III NSCLC: BTCRC LUN16-081.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.5_suppl.tps179 ◽

2018 ◽

Vol 36 (5_suppl) ◽

pp. TPS179-TPS179 ◽

Cited By ~ 1

Author(s):

Greg Andrew Durm ◽

Susan M. Perkins ◽

Nasser H. Hanna

Keyword(s):

Phase Ii ◽

Stage Iv ◽

Standard Of Care ◽

Concurrent Chemoradiation ◽

Stage Iii ◽

Current Standard ◽

Unresectable Stage ◽

Secondary Endpoints ◽

Stage Iii Nsclc ◽

Nsclc Patients

TPS179 Background: Unresectable stage III NSCLC demonstrates poor 5-yr OS outcomes. The current standard of care for fit patients in this setting is concurrent chemoradiation. Previous studies evaluating the addition of induction or consolidation chemotherapy, EGFR-targeted agents, ant-angiogenic agents, and higher doses of radiation have failed to definitively improve OS over chemoradiation alone. Recently, a trial of consolidation PD-L1 inhibition demonstrated improved PFS over chemoradiation alone, and a second trial of consolidation PD-1 inhibition is awaiting data maturation. This may herald a change to the standard of care in this setting. The addition of CTLA-4 inhibition to anti-PD-1 monoclonal antibodies has shown improved OS in melanoma and has demonstrated encouraging early phase data in stage IV NSCLC. Therefore, we initiated a trial evaluating the addition of a CTLA-4 inhibitor to PD-1 inhibition for consolidation treatment of unresectable stage III NSCLC. Methods: This is a multi-center, randomized, phase II study of nivolumab or the combination of nivolumab and ipilimumab as consolidation therapy following concurrent chemoradiation in unresectable stage III NSCLC. Patients will receive concurrent chemoradiation with one of three standard chemotherapy backbones (Cis-Etop, Cis-Pem, or Carbo-Pac), and repeat imaging will be done 4-8 weeks following completion of therapy. Patients without progressive disease will be randomized 1:1 to receive either niv 480mg IV every 4 weeks or the combination of niv 3mg/kg IV every 2 weeks and ipi 1mg/kg IV every 6 weeks for up to 6 months. The trial will enroll a total of 108 patients with 54 in each arm. The two arms are non-comparator arms and will be compared with historical controls. The primary endpoint is the improvement of PFS at 18 months, and key secondary endpoints include OS and the toxicity of consolidation niv and niv/ipi. Exploratory endpoints will look at the correlation between multiple clinical, radiographic, and laboratory parameters and outcomes, as well as the association of these parameters with the development of pneumonitis. This trial opened to accrual in September 2017. Clinical trial information: NCT03285321.

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Phase II trial of atezolizumab before and after definitive chemoradiation for unresectable stage III NSCLC.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.15_suppl.tps8585 ◽

2018 ◽

Vol 36 (15_suppl) ◽

pp. TPS8585-TPS8585 ◽

Cited By ~ 2

Author(s):

Helen J. Ross ◽

David E. Kozono ◽

James John Urbanic ◽

Terence Marques Williams ◽

Carter Dufrane ◽

...

Keyword(s):

Phase Ii ◽

Phase Ii Trial ◽

Stage Iii ◽

Definitive Chemoradiation ◽

Unresectable Stage ◽

Before And After ◽

Stage Iii Nsclc

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P3.04-003 Phase II Trial of Atezolizumab Before and After Definitive Chemoradiation for Patients with Unresectable Stage III NSCLC

Journal of Thoracic Oncology ◽

10.1016/j.jtho.2017.09.1661 ◽

2017 ◽

Vol 12 (11) ◽

pp. S2285-S2286 ◽

Cited By ~ 1

Author(s):

H. Ross ◽

D. Kozono ◽

J. Urbanic ◽

T. Williams ◽

C. Dufrane ◽

...

Keyword(s):

Phase Ii ◽

Phase Ii Trial ◽

Stage Iii ◽

Definitive Chemoradiation ◽

Unresectable Stage ◽

Before And After ◽

Stage Iii Nsclc

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HELPER study: A phase II trial of continuous infusion of endostar combined with concurrent etoposide plus cisplatin and radiotherapy for treatment of unresectable stage III non-small-cell lung cancer

Radiotherapy and Oncology ◽

10.1016/j.radonc.2018.10.032 ◽

2019 ◽

Vol 131 ◽

pp. 27-34 ◽

Cited By ~ 6

Author(s):

Yirui Zhai ◽

Honglian Ma ◽

Zhouguang Hui ◽

Lujun Zhao ◽

Dongming Li ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Continuous Infusion ◽

Phase Ii ◽

Cell Lung Cancer ◽

Phase Ii Trial ◽

Small Cell ◽

Stage Iii ◽

Small Cell Lung ◽

Unresectable Stage

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P-5 A phase II trial of paclitaxel carboplatin and gemcitabine as induction chemotherapy for stage III NSCLC

Lung Cancer ◽

10.1016/s0169-5002(03)91974-x ◽

2003 ◽

Vol 41 ◽

pp. S92

Author(s):

Carmelo Giannitto Giorgio ◽

Salvino Saita ◽

Franco Marletta ◽

Stefano Cordio ◽

Dario Giuffrida ◽

...

Keyword(s):

Induction Chemotherapy ◽

Phase Ii ◽

Phase Ii Trial ◽

Stage Iii ◽

Stage Iii Nsclc

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

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.18070 ◽

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.

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