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.

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.

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.

Phase II study of PS-341 (bortezomib) with or without irinotecan in patients (pts) with advanced gastric adenocarcinomas (AGA)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14040-14040 ◽  
Author(s):  
A. J. Ocean ◽  
F. Schnoll-Sussman ◽  
R. Keresztes ◽  
X. Chen ◽  
S. Holloway ◽  
...  
Keyword(s):  
Overall Survival ◽  
Phase Ii ◽  
Response Rate ◽  
Single Agent ◽  
Xenograft Model ◽  
Progression Free Survival ◽  
Median Number ◽  
Primary Objective ◽  
Free Survival ◽  
Radiologic Evaluation

14040 Background: We are conducting a phase II trial of the proteasome inhibitor, PS-341, with or without irinotecan in pts with AGA. The combination of PS-341 and irinotecan has been studied in preclinical tumor models including a murine xenograft model of colon cancer, where the combination achieved significantly more tumor shrinkage than either agent alone. The primary objective of this study is to determine response rates, toxicities, progression-free survival, and overall survival in pts with AGA receiving PS-341 alone or in combination with irinotecan. Methods: All pts had gastric adenocarcinoma beyond the scope of surgical resection, measurable disease, and normal bone marrow, hepatic and renal function. All gave informed consent. In previously untreated patients, PS-341 was administered at 1.3 mg/m2 on days 1, 4, 8, and 11 as IV bolus every 21 days. Irinotecan was administered IV at 125 mg/m2 over 90 mins on days 1 and 8 every 21 days (Arm A). For previously treated patients, PS-341 was administered as a single agent at 1.3mg/m2 on days 1, 4, 8, 11 as an IV bolus every 21 days (Arm B). Radiologic evaluation and tumor measurements were performed every 8 weeks. Results: Thirty-seven pts have been enrolled; 29 are evaluable (4 never treated, 4 TETE). Twenty-two pts were treated in Arm A, and 11 in Arm B. All pts were eligible and the 29 treated pts were fully evaluable. Median age 58 (33–87); 26 males/7 females; median number of cycles received was 2.0. Most common toxicities: Grade 4 cardiac arrest (1), stomach perforation (1), leukopenia (2), diarrhea (1), edema (1); Grade 3 nausea (6), vomiting (7), diarrhea (4), febrile neutropenia (3), thrombocytopenia (6), anemia (6); Grade 5 death (3). Severe toxicities likely attributed to disease progression. Response rate was 33% for Arm A, 9% for Arm B. Progression-free survival was 1.8 mo. in Arm A, 1.4 mo. in Arm B. Median overall survival was 4.8 mo. in Arm A, 5.4 mo. in Arm B. Conclusions: The combination of PS-341 and irinotecan, a non-cisplatin containing therapy, is active in AGA and should be considered a key regimen. Monotherapy with PS-341 has a 9% response rate in this population of pre-treated patients with advanced disease. Accrual to this study is continuing. [Table: see text]

Gemcitabine Plus Carboplatin Compared With Carboplatin in Patients With Platinum-Sensitive Recurrent Ovarian Cancer: An Intergroup Trial of the AGO-OVAR, the NCIC CTG, and the EORTC GCG

2006 ◽  
Vol 24 (29) ◽  
pp. 4699-4707 ◽  
Author(s):  
Jacobus Pfisterer ◽  
Marie Plante ◽  
Ignace Vergote ◽  
Andreas du Bois ◽  
Hal Hirte ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Ovarian Cancer ◽  
Response Rate ◽  
Single Agent ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Recurrent Ovarian Cancer ◽  
Primary Objective ◽  
Platinum Sensitive

Purpose Most patients with advanced ovarian cancer develop recurrent disease. For those patients who recur at least 6 months after initial therapy, paclitaxel platinum has shown a modest survival advantage over platinum without paclitaxel; however, many patients develop clinically relevant neurotoxicity, frequently resulting in treatment discontinuation. Thus, an alternative regimen without significant neurotoxicity was evaluated by comparing gemcitabine plus carboplatin with single-agent carboplatin in platinum-sensitive recurrent ovarian cancer patients. Methods Patients with platinum-sensitive recurrent ovarian cancer were randomly assigned to receive either gemcitabine plus carboplatin or carboplatin alone, every 21 days. The primary objective was to compare progression-free survival (PFS). Results Three hundred fifty-six patients (178 gemcitabine plus carboplatin; 178 carboplatin) were randomly assigned. Patients received a median of six cycles in both arms. With a median follow-up of 17 months, median PFS was 8.6 months (95% CI, 7.9 to 9.7 months) for gemcitabine plus carboplatin and 5.8 months (95% CI, 5.2 to 7.1 months) for carboplatin. The hazard ration (HR) for PFS was 0.72 (95% CI, 0.58 to 0.90; P = .0031). Response rate was 47.2% (95% CI, 39.9% to 54.5%) for gemcitabine plus carboplatin and 30.9% (95% CI, 24.1% to 37.7%) for carboplatin (P = .0016). The HR for overall survival was 0.96 (95% CI, 0.75 to1.23; P = .7349). While myelosuppression was significantly more common in the combination, sequelae such as febrile neutropenia or infections were uncommon. No statistically significant differences in quality of life scores between arms were noted. Conclusion Gemcitabine plus carboplatin significantly improves PFS and response rate without worsening quality of life for patients with platinum-sensitive recurrent ovarian cancer.

Gefitinib plus celecoxib in chemotherapy-naïve patients with stage IIIB/IV non-small cell lung cancer (NSCLC): A phase II study from the Hoosier Oncology Group

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7066-7066 ◽  
Author(s):  
A. K. Agarwala ◽  
L. Einhorn ◽  
W. Fisher ◽  
D. Bruetman ◽  
J. McClean ◽  
...  
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Study ◽  
Day Treatment ◽  
Single Agent ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Stage Iiib ◽  
Never Smokers ◽  
Ecog Ps

7066 Background: Gefitinib, an inhibitor of the epidermal growth factor receptor (EGFR) pathway, has single agent activity in NSCLC. Preclinical studies demonstrate significant interactions between the EGFR and cyclo-oxygenase 2 (COX-2) pathways and that simultaneous inhibition against NSCLC may have benefits over gefitinib alone. Methods: Eligibility required that pts were chemotherapy-naïve, had stage IIIb (with pleural effusion) or IV NSCLC and an ECOG PS 0–1. Pts received gefitinib 250mg orally daily plus celecoxib 400mg orally every 12 hours. Cycles consisted of 21 day treatment and continued until unacceptable toxicity or progression of disease. The primary objective of this single arm, two-stage, phase II study was to evaluate the overall response rate. If ≤ 10 out of 30 pts achieved a complete (CR) or partial response (PR), the study would be stopped early. If >10 out of 30 pts had a CR or PR, enrollment would continue to 50 pts. Results: From 1/04 to 11/04, 31 pts were enrolled: male/female 13/18; median age 70.8 years (range, 19–93); 67.7% had adenocarcinoma; ECOG PS 0/1 13/18; stage IIIb/IV 2/29; 5 were current smokers, 9 were remote (>30 years) or never smokers, 16 quit smoking > 3 months ago. Median number of cycles was 4 (range, 0–16). 6 pts (19.4%) discontinued therapy due to toxicity, including 3 who died due to treatment. Select grade 3/4 toxicities included: pulmonary (6.5%), hepatic (6.5%), diarrhea (6.5%), skin (3.2%). Responses included PR 5 (16.1%), stable disease 8 (25.8%), and progressive disease 18 (58.1%). Median duration of response, progression free survival, and overall survival was 5.7, 2.8, and 7.2 months, respectively. All responders were females with adenocarcinoma, 2 were remote or never smokers and 3 were former smokers. Conclusion: Gefitinib plus celecoxib in an unselected population of chemotherapy naïve patients with advanced NSCLC and a PS of 0–1 has a lower response rate and overall efficacy compared with historical controls of chemotherapy. [Table: see text]

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.

scholarly journals CTIM-15. PRELIMINARY RESULTS OF A PHASE II STUDY OF NIVOLUMAB WITH HYPOFRACTIONATED RE-RADIATION AND BEVACIZUMAB FOR RECURRENT MGMT METHYLATED GLIOBLASTOMA

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii36-ii36
Author(s):  
Christian Grommes ◽  
Minesh Mehta ◽  
Alexandra Miller ◽  
Mariza Daras ◽  
Anna Piotrowski ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Checkpoint Inhibitors ◽  
Single Agent ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Disease Recurrence ◽  
Primary Objective ◽  
Significant Finding ◽  
Trial Treatment

Abstract Standard of standard of care for glioblastoma (GBM) remains unsatisfactory with universal disease recurrence and a median survival of &lt; 2 years. Immune checkpoint inhibitors (ICI) have shown limited single-agent activity in GBM thus far. GBMs with methylated MGMT promoter and no baseline corticosteroid dependence may be most likely to derive benefit from ICI. The combination of ICIs with radiation has shown promising activity in other human cancers. Combining nivolumab and re-RT/bevacizumab in GBM may augment ICI activity through immunogenic effects of radiation, may reduce the risk of radiation necrosis by addition of bevacizumab at the time of radiation, and may reduce the need for corticosteroids. In this multicenter phase II study, nivolumab is combined with re-irradiation and optional concurrent bevacizumab followed by nivolumab in patients with first recurrence of IDH-wildtype and MGMT methylated glioblastoma. Primary objective is to improve 1-year overall survival (OS) from 33 (based on EORTC 26101) to 50%. Nine-three patients are required to show a significant finding with an α of 0.05 and 81% power. Thirteen of 93 patient (14%) have been enrolled with a median age of 59 (range 42–71) with a median KPS of 90 (range 70–90). Treatment has been tolerated well without any grade ≥ 4 toxicities and only one grade 3 (amylase elevation). The most common adverse events were pruritus and hypothyroidism in 3/13 (23%). The median progression-free survival (PFS) is 7 months with a 6months PFS of 55.6%. The 12months OS is 66.7%. Patients with recurrent MGMT methylated, IDH-wildtype glioblastoma tolerate trial treatment with acceptable toxicities. Clinical efficacy in the first patients enrolled shows a promising effect. Enrollment is ongoing.

scholarly journals Oral vinorelbine and cisplatin as first-line therapy for advanced squamous NSCLC patients: a prospective randomized international phase II study (NAVoTrial 03)

2021 ◽  
Vol 13 ◽  
pp. 175883592110229
Author(s):  
Francesco Grossi ◽  
Piotr Jaśkiewicz ◽  
Marion Ferreira ◽  
Grzegorz Czyżewicz ◽  
Dariusz Kowalski ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Current Knowledge ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Comparable Efficacy ◽  
Open Label ◽  
Oral Vinorelbine ◽  
First Line Therapy ◽  
Nsclc Patients

Objective: The study investigated the efficacy and safety of oral vinorelbine-cisplatin (OV-CDDP) and gemcitabine-cisplatin (GEM-CDDP) in patients with squamous non-small cell lung cancer (sq-NSCLC). Patients and methods: This was an open-label, prospective, multicenter, international phase II study that enrolled untreated patients with advanced sq-NSCLC. Patients were randomized to receive 3-week cycles of either 60–80 mg/m2 OV days 1 and 8 in combination with 80 mg/m2 CDDP day 1 (arm A) or 1250 mg/m2 GEM days 1 and 8 in combination with 75 mg/m2 CDDP day 1 (arm B). After four cycles, patients without disease progression continued maintenance dose of OV or GEM until progression or unacceptable toxicity. The primary objective was disease control rate (DCR). Secondary objectives included progression-free survival (PFS), time to treatment failure (TTF), overall survival (OS), safety, and quality of life (QoL). Results: A total of 114 patients with sq-NSCLC were randomized, and 113 were treated (57 in arm A and 56 in arm B). DCR was high in both arms: 73.7% (95%CI: 62.4–100.0) in arm A and 75.0% (95%CI: 63.7–100.0) in arm B. Median PFS and TTF were similar in arm A and B 4.2 and 2.8 months, and 4.3 and 3.1 months, respectively. Even though the difference was not significant, the OS was 10.2 for arm A and 8.4 months for arm B. The safety profiles were consistent with the current knowledge of adverse events. QoL results revealed an improvement in patients under OV treatment. Conclusion: The OV-CDDP combination showed comparable efficacy to GEM-CDDP with acceptable safety profile and enhanced patients’ QoL. Trial registration: The study was registered under EudraCT number 2012-003531-40.

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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