Final planned overall survival (OS) from OPTiM, a randomized Phase III trial of talimogene laherparepvec (T-VEC) versus GM-CSF for the treatment of unresected stage IIIB/C/IV melanoma (NCT00769704)

17083 Background: Monochemotherapy with gemcitabine (GEM) or vinorelbine is considered the standard treatment in elderly or poor performance (PS) patients (pts) with advanced NSCLC. Many topics report a synergic enhancement of antitumor effect of GEM if associated to Vindesine (VDS). The aim of this study is to evaluate if GEM combined to VDS produces an advantage in terms of overall survival (OS) compared to GEM alone without enhancement of toxicity. Methods: Chemonaive pts with stage IIIB/IV NSCLC, aged ≥ 70 years with PS < 2 or aged < 70 years with PS > 2 were enrolled. Pts were randomized to receive either GEM 1200 mg/m2 day 1 and 8 every 21 days for three cycles (arm 1) or GEM 1000 mg/m2 and VDS 3 mg/m2 (max dose 5 mg) both drugs infused on day 1 and 8 every 21 days for three cycles (arm 2). Pts of both arms received other three cycles in case of responsive or stable disease. Overall survival (OS) was the primary end-point, secondary end-points were time-to-progression and toxicity. First interim analysis was planned at 120 pts enrolled. Results: From May 2002 to December 2005, 107 pts from 13 Italian institutions were enrolled. Their characteristics are: 24 stage IIIB and 83 stage IV, 79 pts with ≥ 70 years (ECOG PS 0–1) and 28 pts with < 70 years (ECOG PS > 2). In arm 1 there were enrolled 55 pts while 52 pts in arm 2: both arms were well balanced with pts characteristics. Conclusions: The enrollment of this phase III trial is ongoing: we are achieving first step for an interim analysis to assess if GEM associated to VDS produces an advantage in terms of OS compared to standard treatment as GEM in monochemotherapy without toxicity enhancement. (Supported by GIVOP: Gruppo Interdisciplinare Veronese di Oncologia Polmonare). No significant financial relationships to disclose.

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Efficacy and tolerability of gemcytabine plus docetaxel in patients with locally advanced or metastatic adenocarcinoma of the lung

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.17134 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 17134-17134

Author(s):

M. Krzakowski ◽

D. M. Kowalski ◽

K. Zajda ◽

T. Denisso ◽

P. Jaskiewicz ◽

...

Keyword(s):

Overall Survival ◽

Total Dose ◽

Median Overall Survival ◽

Locally Advanced ◽

Stage Iv ◽

Stage Iiib ◽

Phase Iii ◽

Second Line Therapy ◽

Phase Iii Trial ◽

Adenocarcinoma Of Lung

17134 Background: Chemotherapy prolongs survival of patients with advanced non-small cell lung cancer (NSCLC). Subanalysis of a phase III trial suggests better outcome of treatment with platinum and gemcytabine containing combinations in patients with adenocarcinoma. Also docetaxel is active in NSCLC. The aim of this phase II trial was to wvaluate the efficacy and tolerability of third generation doublet (GCB and DXL) in cheminaive patients with advanced adenocarcinoma of lung. Methods: Chemonaive patients with biopsy proven stage IIIB or IV adenocarcinoma of lung not suitable for curative radical treatment witk KPS 80–100 received 2 to 6 chemotherapy cycles (DXL 80 mg/m2 day 1 plus GCB 1000 mg/m2 day 1 and 8; every 21 days). Response rate and tolerability were the primary endpionts, while the overall survival and 1-year survival were secondary objectives. Results: Twenty eigth patients (15 women, 13 men) with median age 59,04 (range 40–74) were treated. Twenty three patients was analysed. Stage IV was found in 23 (95.8%) and stage IIIB in 1 (4.2%) patients. Partial response was achiwed in 9 (37,5%), stable disease in 12 (50%) and pregressive disease in 3 (12,5%) patients. Median time to progression was 8, 37 months (range: 1.5–14 months). Median overall survival was 12,87 months (range: 4–35 months). Eleven (11) patients received second-line therapy (6-RT, 11-CTH). All patients received 94 cycles of chemotherapy (range: 2, median 3,9). Total dose of docetaxel on each patients was fro 120 to 960 mg (median 556 mg). Total dose of gemcytabine on each patients was from 2100 mg to 21000 mg (median 10475 mg). Treatment toxicicy presents on the table . Conclusions: First line gemcytabine and docetaxel containing chemotherapy is effective palliative treatment for patients with advanced AC of the lung. Toxicity was within acceptable limits. [Table: see text] No significant financial relationships to disclose.

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OPTiM: A randomized phase III trial of talimogene laherparepvec (T-VEC) versus subcutaneous (SC) granulocyte-macrophage colony-stimulating factor (GM-CSF) for the treatment (tx) of unresected stage IIIB/C and IV melanoma.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.lba9008 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. LBA9008-LBA9008 ◽

Cited By ~ 4

Author(s):

Robert Hans Ingemar Andtbacka ◽

Frances A. Collichio ◽

Thomas Amatruda ◽

Neil N. Senzer ◽

Jason Chesney ◽

...

Keyword(s):

Phase Iii ◽

Talimogene Laherparepvec ◽

Daily News ◽

Phase Iii Trial ◽

Online Supplement ◽

Gm Csf ◽

Macrophage Colony Stimulating Factor ◽

Macrophage Colony ◽

Stimulating Factor ◽

Final Text

LBA9008 The full, final text of this abstract will be available at abstract.asco.org at 7:30 AM (EDT) on Saturday, June, 1, 2013, and in the Annual Meeting Proceedings online supplement to the June 20, 2013, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Saturday edition of ASCO Daily News.

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Patterns of durable response with intralesional talimogene laherparepvec (T-VEC): Results from a phase III trial in patients with stage IIIb-IV melanoma.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.15_suppl.9026 ◽

2014 ◽

Vol 32 (15_suppl) ◽

pp. 9026-9026 ◽

Cited By ~ 4

Author(s):

Merrick I. Ross ◽

Robert Hans Ingemar Andtbacka ◽

Igor Puzanov ◽

Mohammed M. Milhem ◽

Frances A. Collichio ◽

...

Keyword(s):

Stage Iiib ◽

Phase Iii ◽

Talimogene Laherparepvec ◽

Durable Response ◽

Phase Iii Trial

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OPTiM: A randomized phase III trial of talimogene laherparepvec (T-VEC) versus subcutaneous (SC) granulocyte-macrophage colony-stimulating factor (GM-CSF) for the treatment (tx) of unresected stage IIIB/C and IV melanoma.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.18_suppl.lba9008 ◽

2013 ◽

Vol 31 (18_suppl) ◽

pp. LBA9008-LBA9008 ◽

Cited By ~ 56

Author(s):

Robert Hans Ingemar Andtbacka ◽

Frances A. Collichio ◽

Thomas Amatruda ◽

Neil N. Senzer ◽

Jason Chesney ◽

...

Keyword(s):

Interim Analysis ◽

Response Rate ◽

Objective Response ◽

Distant Metastases ◽

Complete Response ◽

Stage Iiib ◽

Phase Iii ◽

Durable Response ◽

Phase Iii Trial ◽

Gm Csf

LBA9008 Background: T-VEC is an oncolytic immunotherapy (OI) derived from herpes simplex virus type-1 designed to selectively replicate within tumors and to produce GM-CSF to enhance systemic antitumor immune responses. OPTiM is a randomized, phase III trial of T-VEC or GM-CSF in patients (pts) with unresected melanoma with regional or distant metastases. We report the primary results of the first phase III study of OI. Methods: Key criteria: age ≥18 yrs; ECOG ≤1; unresectable melanoma stage IIIB/C or IV; injectable cutaneous, SC, or nodal lesions; LDH ≤1.5X upper limit of normal; ≤3 visceral lesions (excluding lung), none >3 cm. Pts were randomized 2:1 to intralesional T-VEC (initially ≤ 4 mL x106 pfu/mL then after 3 wks, ≤ 4 mL x108 pfu/mL Q2W) or SC GM-CSF (125 µg/m2qd x 14 days q28d). The primary endpoint was durable response rate (DRR): partial or complete response (CR) continuously for ≥6 mos starting within 12 mos. Responses were per modified WHO by blinded central review. A planned interim analysis of overall survival (OS; key secondary endpoint) was performed. Results: 436 pts are in the ITT set: 295 (68%) T-VEC, 141 (32%) GM-CSF. 57% were men; median age was 63 yrs. Stage distribution was: IIIB/C 30%, IVM1a 27%, IVM1b 21%, IVM1c 22%. Objective response rate with T-VEC was 26% (95% CI: 21%, 32%) with 11% CR, and with GM-CSF was 6% (95% CI: 2%, 10%) with 1% CR. DRR for T-VEC was 16% (95% CI: 12%, 21%) and 2% for GM-CSF (95% CI: 0%, 5%), p<0.0001. DRR by stage (T-VEC, GM-CSF) was IIIB/C (33%, 0%), M1a (16%, 2%), M1b (3%, 4%), and M1c (8%, 3%). Interim OS showed a trend in favor of T-VEC; HR 0.79 (95% CI: 0.61, 1.02). Most common adverse events (AEs) with T-VEC were fatigue, chills, and pyrexia. Serious AEs occurred in 26% of T-VEC and 13% of GM-CSF pts. No ≥ grade 3 AE occurred in ≥ 3% of pts in either arm. Conclusions: T-VEC demonstrated both a statistically significant improvement in DRR over GM-CSF in pts with unresectable stage IIIB-IV melanoma and a tolerable safety profile; an interim analysis showed a trend toward improved OS. T-VEC represents a novel potential tx option for melanoma with regional or distant metastases. Clinical trial information: NCT00769704.

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Talimogene Laherparepvec Improves Durable Response Rate in Patients With Advanced Melanoma

Journal of Clinical Oncology ◽

10.1200/jco.2014.58.3377 ◽

2015 ◽

Vol 33 (25) ◽

pp. 2780-2788 ◽

Cited By ~ 1101

Author(s):

Robert H.I. Andtbacka ◽

Howard L. Kaufman ◽

Frances Collichio ◽

Thomas Amatruda ◽

Neil Senzer ◽

...

Keyword(s):

Overall Response Rate ◽

Response Rate ◽

Objective Response ◽

Stage Iiib ◽

Phase Iii ◽

Talimogene Laherparepvec ◽

Durable Response ◽

Overall Response ◽

Gm Csf ◽

Oncolytic Immunotherapy

Purpose Talimogene laherparepvec (T-VEC) is a herpes simplex virus type 1–derived oncolytic immunotherapy designed to selectively replicate within tumors and produce granulocyte macrophage colony-stimulating factor (GM-CSF) to enhance systemic antitumor immune responses. T-VEC was compared with GM-CSF in patients with unresected stage IIIB to IV melanoma in a randomized open-label phase III trial. Patients and Methods Patients with injectable melanoma that was not surgically resectable were randomly assigned at a two-to-one ratio to intralesional T-VEC or subcutaneous GM-CSF. The primary end point was durable response rate (DRR; objective response lasting continuously ≥ 6 months) per independent assessment. Key secondary end points included overall survival (OS) and overall response rate. Results Among 436 patients randomly assigned, DRR was significantly higher with T-VEC (16.3%; 95% CI, 12.1% to 20.5%) than GM-CSF (2.1%; 95% CI, 0% to 4.5%]; odds ratio, 8.9; P < .001). Overall response rate was also higher in the T-VEC arm (26.4%; 95% CI, 21.4% to 31.5% v 5.7%; 95% CI, 1.9% to 9.5%). Median OS was 23.3 months (95% CI, 19.5 to 29.6 months) with T-VEC and 18.9 months (95% CI, 16.0 to 23.7 months) with GM-CSF (hazard ratio, 0.79; 95% CI, 0.62 to 1.00; P = .051). T-VEC efficacy was most pronounced in patients with stage IIIB, IIIC, or IVM1a disease and in patients with treatment-naive disease. The most common adverse events (AEs) with T-VEC were fatigue, chills, and pyrexia. The only grade 3 or 4 AE occurring in ≥ 2% of T-VEC–treated patients was cellulitis (2.1%). No fatal treatment-related AEs occurred. Conclusion T-VEC is the first oncolytic immunotherapy to demonstrate therapeutic benefit against melanoma in a phase III clinical trial. T-VEC was well tolerated and resulted in a higher DRR (P < .001) and longer median OS (P = .051), particularly in untreated patients or those with stage IIIB, IIIC, or IVM1a disease. T-VEC represents a novel potential therapy for patients with metastatic melanoma.

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