An international, randomized, phase III trial of bacillus Calmette-Guerin (BCG) plus allogeneic melanoma vaccine (MCV) or placebo after complete resection of melanoma metastatic to regional or distant sites

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8508-8508 ◽  
Author(s):  
D. L. Morton ◽  
N. Mozzillo ◽  
J. F. Thompson ◽  
M. C. Kelley ◽  
M. Faries ◽  
...  
Keyword(s):  
Immune Responses ◽  
Residual Disease ◽  
Disease Free Survival ◽  
Stage Iv ◽  
Intradermal Injection ◽  
Phase Iii ◽  
Stage Iii ◽  
Cell Vaccine ◽  
Regional Lymph Nodes ◽  
Entire Study

8508 Background: Active specific immunotherapy with BCG and an allogeneic, melanoma cell vaccine can induce antibody and T-lymphocyte immune responses to numerous antigens expressed by melanoma cells. This study compared overall and disease-free survival in patients receiving BCG plus placebo versus BCG plus MCV. Methods: Between June 1998 and November 2005, 1,656 patients without evidence of residual disease after resection of stage III (n = 1,160) or stage IV (n = 496) melanoma were randomly assigned to the two treatment arms (1:1). BCG was given as an immunologic adjuvant for the first two injections of both MCV and placebo, which thereafter were administered by intradermal injection every two weeks for the next three injections, every month for the remainder of the first year, every two months for the second year and every three months for years three, four and five. Results: Based on the recommendation of the independent Data and Safety Monitoring Board (DSMB), both studies were terminated after the interim analysis. The recommendation was based on a low probability of demonstrating significant improvement in survival of the BCG plus MCV arm if the study had continued to completion of follow-up and final analysis. Conclusions: This is the largest multicenter clinical trial of postoperative adjuvant immunotherapy after resection of melanoma metastatic to regional lymph nodes or distant sites. It is a landmark study not only because it represents the first randomized multicenter trial to use surgical resection as initial therapy for stage IV melanoma patients with up to five metastatic sites, but also because its results demonstrate excellent survival for the entire study population with 42.3% of stage IV and 63.4% of stage III patients projected to be alive at five years. Updated data for survival and immunologic endpoints which show a significant correlation between immune responses and survival will be provided at the meeting. [Table: see text]

Minimal Macroscopic Residual Disease (0.1–1 cm). Is It Still a Surgical Goal in Advanced Ovarian Cancer?

2016 ◽  
Vol 26 (5) ◽  
pp. 906-911 ◽  
Author(s):  
Luis M. Chiva ◽  
Teresa Castellanos ◽  
Sonsoles Alonso ◽  
Antonio Gonzalez-Martin
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Median Overall Survival ◽  
Residual Disease ◽  
Disease Free Survival ◽  
Advanced Ovarian Cancer ◽  
Stage Iv ◽  
Phase Iii ◽  
Stage Iii ◽  
Pubmed Database

ObjectiveThe objective of this review was to try to determine by searching in the literature what is the survival in patients with advanced ovarian cancer after a primary debulking with minimal macroscopic residual disease (MMRD; 0.1–10 mm). Additionally, this review aimed to explore the survival in patients with residual disease from 0.1 to 0.5 cm.MethodsA retrospective search was accomplished in the PubMed database looking for all English-language articles published between January 1, 2007 and December 31, 2014, under the following search strategy: “ovarian cancer and cytoreduction” or “ovarian cancer and phase III trial”. We selected those articles that contain information on both percentage of MMRD (0.1–1 cm) and median overall survival (OS) in this subset of patients with stage III to stage IV ovarian cancer after primary debulking surgery.ResultsThirteen publications were obtained including information of a total 11,999 patients with stage III to stage IV ovarian cancer. Five thousand thirty-seven patients (42%) had MMRD after the primary debulking (0.1–1 cm). Median overall survival in patients with MMRD was 40 months and disease-free survival (DFS) was 16 months. This group of patients obtained an advantage of 10 months in OS (40 vs 30 m) and 4 months in DFS (16 vs 12 m) compared with the group with suboptimal debulking (P < 0.001). Compared with the group of complete resection, patients with minimal macroscopic residuum showed a significant inferior median OS and DFS of 30 months and 14 months, respectively (OS, 70 vs 40 m; DFS, 30 vs 16 m) (P < 0.001). The group of residual disease of 0.1 to 0.5 cm reached a median survival of 53 months.ConclusionsPatients with ovarian cancer with MMRD after primary surgery obtain a modest but significant advantage in survival (10 months) over suboptimal patients. Patients with macroscopic residual disease (0.1–0.5 cm) obtain a better survival (53 months) than those with more than 0.5 to 1 cm. We propose that they should be classified as a different prognostic group.

scholarly journals Genetic Variants in Immune Related Genes as Predictors of Responsiveness to BCG Immunotherapy in Metastatic Melanoma Patients

Cancers ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 91
Author(s):  
Romela Irene Ramos ◽  
Misa A. Shaw ◽  
Leland Foshag ◽  
Stacey L. Stern ◽  
Negin Rahimzadeh ◽  
...  
Keyword(s):  
Immune Responses ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Stage Iii ◽  
Immune Gene ◽  
Nucleotide Polymorphisms ◽  
Predictive Tool ◽  
Immune Genes ◽  
Ajcc Stage ◽  
Melanoma Patients

Adjuvant immunotherapy in melanoma patients improves clinical outcomes. However, success is unpredictable due to inherited heterogeneity of immune responses. Inherent immune genes associated with single nucleotide polymorphisms (SNPs) may influence anti-tumor immune responses. We assessed the predictive ability of 26 immune-gene SNPs genomic panels for a clinical response to adjuvant BCG (Bacillus Calmette-Guérin) immunotherapy, using melanoma patient cohorts derived from three phase III multicenter clinical trials: AJCC (American Joint Committee on Cancer) stage IV patients given adjuvant BCG (pilot cohort; n = 92), AJCC stage III patients given adjuvant BCG (verification cohort; n = 269), and AJCC stage III patients that are sentinel lymph node (SLN) positive receiving no immunotherapy (control cohort; n = 80). The SNP panel analysis demonstrated that the responder patient group had an improved disease-free survival (DFS) (hazard ratio [HR] 1.84, 95% CI 1.09–3.13, p = 0.021) in the pilot cohort. In the verification cohort, an improved overall survival (OS) (HR 1.67, 95% CI 1.07–2.67, p = 0.025) was observed. No significant differences of SNPs were observed in DFS or OS in the control patient cohort. This study demonstrates that SNP immune genes can be utilized as a predictive tool for identifying melanoma patients that are inherently responsive to BCG and potentially other immunotherapies in the future.

scholarly journals 310 The effect of pretreatment with G-CSF prior to dendritic cell collection during the phase IIb trial of an autologous DC-based vaccine for advanced, resectable melanoma

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A337-A337
Author(s):  
Anne O’Shea ◽  
Robert Chick ◽  
Guy Clifton ◽  
Timothy Vreeland ◽  
Lexy Adams ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
Subgroup Analysis ◽  
Checkpoint Inhibitors ◽  
Disease Free Survival ◽  
Stage Iv ◽  
Phase Iii ◽  
Stage Iii ◽  
Tumor Lysate ◽  
Double Blind ◽  
The Impact

BackgroundWe have completed a prospective, randomized, multi-center, double-blind, placebo-controlled phase IIb trial of the tumor lysate, particle loaded, dendritic cell (TLPLDC) vaccine given to prevent recurrences in patients with resected stage III/IV melanoma. During the trial, granulocyte colony stimulating factor (G-CSF) was administered to some patients to mobilize dendritic cells (DCs) precursors prior to harvest, allowing for similar DC yield with reduced blood draws. This study examines the impact of DC collection methods on vaccine effectiveness.MethodsTLPLDC is produced by loading tumor lysate into pre-prepared yeast cell wall particles (YCWPs) and exposing them to autologous DCs. DC precursors were isolated either by collection of 50–70 mL of blood following pre-administration of 300µg of G-CSF 24–48 hrs prior, or collection of 120 mL of peripheral blood without G-CSF pretreatment based on patient and provider preference. Patients were randomized 2:1 to receive TLPLDC or placebo (DCs exposed to empty YCWPs). 1–1.5 × 106 cells/dose were injected intradermally at 0, 1, 2, 6, 12, and 18 months. Differences in disease free survival (DFS) and overall survival (OS) were analyzed by log rank.ResultsOf 144 patients randomized, 103 received TLPLDC and 41 received placebo. Within the TLPLDC group, 57 received pretreatment with G-CSF (TLPLDC+G-CSF) and 46 did not (TLPLDC–G-CSF). There were no significant clinicopathologic or treatment differences between the three treatment arms. 36-month DFS was significantly better in TLPLDC–G-CSF vs. TLPLDC+G-CSF or placebo (51.8% vs. 23.4% and 27.1% respectively, p=0.027) (figure 1). TLPLDC–G-CSF had correspondingly improved OS (92.9% vs. 62.8% and 72.3% respectively, p=0.022) (figure 2). Subgroup analysis revealed TLPLDC–G-CSF had increased DFS over TLPLDC+G-CSF or placebo in Stage IV (68.6% vs. 18.8% and 0.0% respectively, p=0.058). Similarly, the DFS survival benefit of TLPLDC–G-CSF was enhanced in patients who received prior immunotherapy (IO) (61.9% vs. 11.5% and 35.7% respectively, p=0.007) or checkpoint inhibitors (CPI) (48.5% vs. 10.6% and 37.5% respectively, p=0.039).Abstract 310 Figure 1DFS at 36 monthsAbstract 310 Figure 2OS at 36 monthsConclusionsTLPLDC vaccine created without G-CSF pretreatment significantly improved 36-month DFS and OS compared to TLPLDC+G-CSF or placebo in stage III/IV (resected) melanoma patients. On further subgroup analysis, the increases in OS and DFS were more profound in patients who received additional immune therapies to include CPI. Ongoing evaluation will determine if G-CSF mobilization leads to collection of phenotypically different DCs. Based on these results, we are planning a phase III trial of TLPLDC–G-CSF + CPI vs. placebo + CPI in advanced melanoma post-resection.Trial RegistrationClinicalTrials. gov Identifier: NCT02301611Ethics ApprovalThis study was reviewed and approved by the IRB or Independent Ethics Committee (IEC) of each participating center prior to study initiation.

Progression-free survival (PFS) and second PFS (PFS2) by disease stage in patients (pts) with homologous recombination deficiency (HRD)-positive newly diagnosed advanced ovarian cancer receiving bevacizumab (bev) with olaparib/placebo maintenance in the phase III PAOLA-1/ENGOT-ov25 trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5514-5514
Author(s):  
Patricia Pautier ◽  
Philipp Harter ◽  
Carmela Pisano ◽  
Claire Cropet ◽  
Susana Hernando Polo ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Residual Disease ◽  
Stage Iv ◽  
Figo Stage ◽  
Phase Iii ◽  
Stage Iii ◽  
Disease Stage ◽  
Newly Diagnosed ◽  
Platinum Based Chemotherapy ◽  
Interval Surgery

5514 Background: In the Phase III PAOLA-1/ENGOT-ov25 trial (NCT02477644), the addition of maintenance olaparib to bev in pts with newly diagnosed advanced high-grade ovarian cancer (HGOC) resulted in a significant PFS benefit, particularly in HRD-positive (HRD+) pts (hazard ratio [HR] 0.33; 95% CI 0.25–0.45) (Ray-Coquard et al. NEJM 2019). We explored efficacy in HRD+ pts by disease stage. Methods: Pts with newly diagnosed, FIGO stage III–IV HGOC in response after platinum-based chemotherapy + bev received bev (15 mg/kg q3w for 15 months [mo]) + either olaparib (300 mg bid for 24 mo) or placebo (pbo). This exploratory analysis evaluated PFS (data cut-off [DCO]: Mar 22 2019) and PFS2 (DCO: Mar 22 2020) in HRD+ pts (tumor BRCA1/ BRCA2 mutation [tBRCAm] or genomic instability score [Myriad myChoice HRD Plus] ≥42) by FIGO stage. Results: 387/806 randomized pts (48%) were HRD+; 272/387 (70%) had stage III disease and 115/387 (30%) had stage IV disease. 153 (56%) HRD+ stage III pts and 61 (53%) HRD+ stage IV pts had a tBRCAm. Among HRD+ stage III pts, 172 (63%) had upfront surgery (51/172 [30%] had residual disease) and 90 (33%) had interval surgery (19/90 [21%] had residual disease); 52 (45%) HRD+ stage IV pts had upfront surgery (34/52 [65%] had residual disease) and 55 (48%) had interval surgery (18/55 [33%] had residual disease). Median follow-up for PFS and PFS2 was respectively 24.8 and 37.2 mo in HRD+ stage III pts and 24.0 and 37.0 mo in HRD+ stage IV pts. Median PFS, PFS2 and HRs are in the Table. Among HRD+ stage III pts, 36-mo PFS2 (olaparib + bev vs pbo + bev) was 74% vs 60%; among HRD+ stage IV pts, 53% vs 30%. Among HRD+ stage III pts with no residual disease after upfront surgery, HR (95% CI) for PFS was 0.15 (0.07–0.30) and for PFS2 was 0.22 (0.06–0.67). Among HRD+ stage III pts with residual disease after upfront surgery or who received neoadjuvant chemotherapy, or HRD+ stage IV pts, HR (95% CI) for PFS was 0.38 (0.27–0.53) and PFS2 was 0.68 (0.46–1.03). Conclusions: In the PAOLA-1 study, maintenance olaparib + bev provided a PFS and PFS2 benefit over pbo + bev in HRD+ pts, irrespective of FIGO stage and residual disease after upfront surgery. Clinical trial information: NCT02477644. [Table: see text]

Phase III trial of bevacizumab (BEV) in the primary treatment of advanced epithelial ovarian cancer (EOC), primary peritoneal cancer (PPC), or fallopian tube cancer (FTC): A Gynecologic Oncology Group study.

2010 ◽  
Vol 28 (18_suppl) ◽  
pp. LBA1-LBA1 ◽  
Author(s):  
R. A. Burger ◽  
M. F. Brady ◽  
M. A. Bookman ◽  
J. L. Walker ◽  
H. D. Homesley ◽  
...  
Keyword(s):  
Residual Disease ◽  
Gynecologic Oncology ◽  
Single Agent ◽  
Stage Iv ◽  
Phase Iii ◽  
Stage Iii ◽  
Gynecologic Oncology Group ◽  
Fallopian Tube Cancer ◽  
Phase Iii Trial ◽  
Grade 3

LBA1 Background: BEV, a humanized anti-VEGF monoclonal antibody, has demonstrated single-agent activity in patients with recurrent EOC, or PPC. The therapeutic impact of concurrent ± maintenance BEV with standard chemotherapy (CT) was evaluated in an international, double-blind, placebo-controlled phase III trial. Methods: Eligible patients had newly diagnosed, previously untreated EOC, PPC or FTC following abdominal surgery for staging and maximal effort at tumor debulking; stage III (macroscopic residual disease) or stage IV disease. The randomly allocated regimens were (1) CT (IV paclitaxel 175 mg/m2 + carboplatin AUC 6 cycles 1-6) + placebo cycles (C)2-22 (R1) (2) CT + concurrent BEV (15 mg/kg) C2-6 + placebo C7-22 (R2) (3) CT + concurrent BEV C2-6 + maintenance BEV C7-22 (R3) Infusions were administered d1 of a 21d cycle. The primary endpoint is progression-free survival (PFS) (radiographic, CA125, clinical criteria or death); secondary endpoints include overall survival, safety, and QoL. Results: 1,873 patients, median age 60, were enrolled from 9/05 - 6/09. Stage III optimally debulked (34%), stage III sub-optimally debulked (40%), and stage IV (26%) patients were similarly distributed in each treatment group. Grade 3 - 4 hypertension was reported in 1.6% (R1), 5.4% (R2), and 10.0% (R3). Grade ≥ 3 GI perforation, hemorrhage or fistula occurred in 0.8% (R1), 2.6% (R2) and 2.3% (R3). Relative to R1, the hazard of first progression or death for R2 was 0.908 (95% CI: 0.795 – 1.04, p=0.16) and for R3 was 0.717 (95% CI: 0.625 – 0.824, p<0.0001). Conclusions: This study demonstrates that front-line treatment of EOC, PPC, and FTC patients with CT plus concurrent and maintenance BEV prolongs PFS. This is the first anti-angiogenic agent to demonstrate benefit in this population. [Table: see text]

Eight Cycles of ABVD Versus Four Cycles of BEACOPPescalated Plus Four Cycles of BEACOPPbaseline in Stage III to IV, International Prognostic Score ≥ 3, High-Risk Hodgkin Lymphoma: First Results of the Phase III EORTC 20012 Intergroup Trial

2016 ◽  
Vol 34 (17) ◽  
pp. 2028-2036 ◽  
Author(s):  
Patrice Carde ◽  
Matthias Karrasch ◽  
Catherine Fortpied ◽  
Pauline Brice ◽  
Hussein Khaled ◽  
...  
Keyword(s):  
High Risk ◽  
Prognostic Score ◽  
Disease Free Survival ◽  
Stage Iv ◽  
Complete Response ◽  
Phase Iii ◽  
Stage Iii ◽  
Free Survival ◽  
International Prognostic Score ◽  
Disease Free

Purpose To compare patients with high-risk stage III to IV Hodgkin lymphoma (HL) in the phase III European Organisation for Research and Treatment of Cancer 20012 Intergroup trial (Comparison of Two Combination Chemotherapy Regimens in Treating Patients With Stage III or Stage IV Hodgkin’s Lymphoma) who were randomly assigned to either doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) or to bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP). Patients and Methods Patients with clinical stage III or IV HL, International Prognostic Score of 3 or higher, and age 60 years or younger received ABVD for eight cycles (ABVD8) or escalated-dose BEACOPP (BEACOPPescalated) for four cycles followed by baseline BEACOPP (BEACOPPbaseline) for four cycles (BEACOPP4+4) without radiotherapy. Primary end points were event-free survival (EFS), treatment discontinuation, no complete response (CR) or unconfirmed complete response (CRu) after eight cycles, progression, relapse, or death. Secondary end points were CR rate, overall survival (OS), quality of life, secondary malignancies, and disease-free survival in CR/CRu patients. Results Between 2002 and 2010, 549 patients were randomly assigned to ABVD8 (n = 275) or BEACOPP4+4 (n = 274). Other characteristics included median age, 35 years; male, 75%; stage IV, 74%; “B” symptoms, 81%; and International Prognostic Score ≥ 4, 59%. WHO performance status was 0 (34%), 1 (48%), or 2 (17%). Median follow-up was 3.6 years. CR/CRu was 82.5% in both arms. At 4 years, EFS was 63.7% for ABVD8 versus 69.3% for BEACOPP4+4 (hazard ratio [HR], 0.86; 95% CI, 0.64 to 1.15; P = .312); disease-free survival was 85.8% versus 91.0% (HR, 0.59; 95% CI, 0.33 to 1.06; P = .076), and OS was 86.7% versus 90.3% (HR, 0.71; 95% CI, 0.42 to 1.21; P = .208). Death as a result of toxicity occurred in six and five patients, early discontinuation (before cycle 5) in 12 and 26 patients, treatment crossovers in five and 10 patients, and secondary malignancies in eight and 10 patients in the ABVD8 and BEACOPP4+4 arms, respectively. Conclusion ABVD8 and BEACOPP4+4 resulted in similar EFS and OS in patients with high-risk advanced-stage HL. Because BEACOPP4+4 did not demonstrate a favorable effectiveness or toxicity ratio compared with ABVD8, treatment burden, immediate and late toxicities, and associated costs must be considered before selecting one of these regimens on which to build future treatment strategies.

Carboplatin and chlorambucil combination chemotherapy as treatment for patients with ovarian cancer

1994 ◽  
Vol 4 (1) ◽  
pp. 66-71
Author(s):  
B. D. Evans ◽  
P. Chapman ◽  
P. Dady ◽  
G. Forgeson ◽  
D. Perez ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Small Volume ◽  
Residual Disease ◽  
Stage Iv ◽  
Complete Response ◽  
Stage Ii ◽  
Stage Iii ◽  
Actuarial Survival ◽  
Moderate Volume ◽  
Grade Iii

Fifty-six patients with ovarian cancer (three stage IC, nine stage II, 33 stage III and II stage IV) were treated with carboplatin 350 mg m−2 i.v. day 1 and chlorambucil orally 0.15 mg kgm−1 days 1–7 inclusive, repeated every 28 days for eight courses. The regimen was well tolerated and was virtually free of nephro- and neurotoxicity. Grade III or IV hematology toxicity occurred in 18 patients but only 31 or 330 courses administered were delayed. Of 40 assessable patients eight achieved a clinical/radiologic complete response and 17 a clinical/radiologic partial response. Actuarial survival at 50 months was 65% for stage II patients, 27% for stage III patients and no stage IV patients survived beyond 20 months. Forty-two per cent of patients with residual disease less 2 cm survived 50 months, compared with 44% of patients with moderate volume (2–5 cm) residual disease and 6% of patients with bulk residual disease. This is an active, well tolerated regimen. However, only patients with small volume residual disease have a significant chance of prolonged survival.

scholarly journals 300 Final analysis of a prospective, randomized, double-blind, placebo-controlled phase IIb trial of tumor lysate, particle-loaded, dendritic cell vaccine in stage III/IV melanoma: 36-month analysis

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A327-A327
Author(s):  
Lexy Adams ◽  
Robert Chick ◽  
Guy Clifton ◽  
Timothy Vreeland ◽  
Patrick McCarthy ◽  
...  
Keyword(s):  
Disease Free Survival ◽  
Stage Iv ◽  
Standard Of Care ◽  
Stage Iii ◽  
Tumor Lysate ◽  
Double Blind ◽  
Free Survival ◽  
Resected Stage ◽  
Disease Free ◽  
Stage Iv Melanoma

BackgroundThe tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine is created ex vivo by loading autologous dendritic cells (DC) with yeast cell wall particles (YCWP) containing autologous tumor lysate, thus delivering tumor antigens to the DC cytoplasm via phagocytosis. TLPLDC then activates a robust T cell response against the unique antigens for each patient. The primary analysis of the prospective, randomized, multi-center, double-blind, placebo-controlled phase IIb trial in patients with resected stage III/IV melanoma showed TLPLDC improved 24-month disease-free survival (DFS) in the per-treatment (PT) analysis (patients completing the 6-month primary vaccine series). Here, we examine the secondary endpoint of 36-month DFS and overall survival (OS).MethodsPatients with resected stage III/IV melanoma were randomized 2:1 to TLPLDC vaccine or placebo (autologous DC loaded with empty YCWP). Treatments were given at 0, 1, 2, 6, 12 and 18 months. The protocol was amended to include patients receiving concurrent checkpoint inhibitors (CPIs) to follow changes in standard of care. The co-primary endpoints were 24-month DFS by intention-to-treat (IT) analysis and per-treatment (PT) analysis, with secondary endpoints including 36-month DFS and OS by ITT and PT analysis, pre-specified analysis by stage, and safety as measured by CTCAE v4.03.ResultsOverall, 103 patients received TLPLDC and 41 placebo. In PT analysis, 65 patients received TLPLDC and 32 placebo. Total adverse events (AEs), grade 3+ AEs, and serious AEs (SAEs) were similar in placebo vs TLPLDC groups, with one related SAE per treatment arm. By ITT analysis, 36-month OS was 76.2% for TLPLDC vs 70.3% for placebo (HR 0.72, p=0.437) and 36-month DFS was 35.6% vs 27.1% (HR 0.95, p=0.841). By PT analysis, 36-month DFS was improved with TLPLDC (57.5% vs 35.0%; HR 0.50, p=0.025, figure 1). This effect was even more dramatic in resected stage IV patients (36-month DFS: 60.9% vs 0%; HR 0.12, p=0.001, figure 2).ConclusionsThis phase IIb trial again demonstrates the safety of the TLPLDC vaccine, and an improved 36-month DFS in patients with resected stage III/IV melanoma who complete the primary vaccine series, particularly in the stage IV subgroup. Next, a phase III trial will evaluate the efficacy of TLPLDC vaccine as adjuvant treatment for resected stage IV melanoma, with patients randomized to receive standard of care PD-1 inhibitors + TLPLDC versus PD-1 inhibitors + placebo.Abstract 300 Figure 136-month disease free survival for patients receiving TLPLDC vs placebo by PT analysisAbstract 300 Figure 236-month disease free survival for subset of stage IV melanoma patients receiving TLPLDC vs placebo by PT analysisTrial RegistrationThis is a phase IIb clinical trial registered under NCT02301611Ethics ApprovalThis study was approved by Western IRB, protocol 20141932.

Three Versus 6 Months of Oxaliplatin-Based Adjuvant Chemotherapy for Patients With Stage III Colon Cancer: Disease-Free Survival Results From a Randomized, Open-Label, International Duration Evaluation of Adjuvant (IDEA) France, Phase III Trial

2018 ◽  
Vol 36 (15) ◽  
pp. 1469-1477 ◽  
Author(s):  
Thierry André ◽  
Dewi Vernerey ◽  
Laurent Mineur ◽  
Jaafar Bennouna ◽  
Jérôme Desrame ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Health Care Providers ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Stage Iii ◽  
Care Providers ◽  
Free Survival ◽  
Stage Iii Colon Cancer ◽  
Disease Free

Purpose Reduction of adjuvant treatment duration may decrease toxicities without loss of efficacy in stage III colon cancer. This could offer clear advantages to patients and health care providers. Methods In International Duration Evaluation of Adjuvant Chemotherapy (IDEA) France, as part of the IDEA international collaboration, patient with colon cancer patients were randomly assigned to 3 and 6 months of modified FOLFOX6 (mFOLFOX6: infusional fluorouracil, leucovorin, and oxaliplatin) or capecitabine plus oxaliplatin (CAPOX) by physician choice. The primary end point was disease-free survival (DFS), and analyses were descriptive. Results A total of 2,010 eligible patients received either 3 or 6 months of chemotherapy (modified intention-to-treat population); 2,000 (99%) had stage III colon cancer (N1: 75%, N2: 25%); 1,809 (90%) received mFOLFOX6, and 201 (10%) received CAPOX. The median age was 64 years, and the median follow-up time was 4.3 years. Overall, 94% (3 months) and 78% (6 months) of patients completed treatment (fluoropyrimidines ± oxaliplatin). Maximal grade 2 and 3 neuropathy rates were 28% and 8% in the 3-month arm and 41% and 25% in the 6-month arm ( P < .001). Final rates of residual neuropathy greater than grade 1 were 3% in the 3-month arm and 7% in the 6-month arm ( P < .001). There were 578 DFS events: 314 and 264 in the 3- and 6-month arms, respectively. The 3-year DFS rates were 72% and 76% in the 3- and 6-month arms, respectively (hazard ratio [HR], 1.24; 95% CI, 1.05 to 1.46; P = .0112). In the 3 and 6-month arms, respectively, for patients who received mFOLFOX6, the 3-year DFS rates were 72% and 76% (HR, 1.27; 95% CI, 1.07 to 1.51); for the T4 and/or N2 population, they were 58% and 66% (HR, 1.44; 95% CI, 1.14 to 1.82); and for the T1-3N1 population, they were 81% and 83% (HR, 1.15; 95% CI, 0.89 to 1.49). Conclusion IDEA France, in which 90% of patients received mFOLFOX6, shows superiority of 6 months of adjuvant chemotherapy compared with 3 months, especially in the T4 and/or N2 subgroups. These results should be considered alongside the international IDEA collaboration data.

scholarly journals Is microsatellite instability-high really a favorable prognostic factor for advanced colorectal cancer? A meta-analysis

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Bingyan Wang ◽  
Fei Li ◽  
Xin Zhou ◽  
Yanpeng Ma ◽  
Wei Fu
Keyword(s):  
Colorectal Cancer ◽  
Beneficial Effect ◽  
Microsatellite Instability ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Stage Iv ◽  
Stage Iii ◽  
Beneficial Result ◽  
Beneficial Effects

Abstract Background Stage II colorectal cancer with microsatellite instability-high (MSI-H) has been proven to have a better prognosis. However, in advanced stage, this trend remains controversial. This study aimed to explore the prognostic role of MSI-H in stage III and IV colorectal cancer (CRC) through meta-analysis. Methods A comprehensive search was performed in PubMed, Cochrane Central Library, and Embase databases. All randomized clinical trials and non-randomized studies were included based on inclusion and exclusion criteria and on survival after a radical operation with or without chemotherapy. The adjusted log hazard ratios (HRs) were used to estimate the prognostic value between MSI-H and microsatellite-stable CRCs. The random-effects model was used to estimate the pooled effect size. Results Thirty-six studies were included. Randomized controlled trials (RCT) and non-RCT were analyzed separately. For stage III CRCs, pooled HR for overall survival (OS) was 0.96 (95% confidence interval [CI] 0.75–.123) in the RCT subgroup and 0.89 (95% CI 0.62–1.28) in the non-RCT subgroup. For disease-free survival (DFS), the HR for the RCT group was 0.83 (95% CI 0.65–1.07), similar to the non-RCT subgroup (0.83, 95% CI 0.65–1.07). Disease-specific survival (DSS) was also calculated, which had an HR of 1.07 (95% CI 0.68–1.69) in the non-RCT subgroup. All these results showed that MSI-H has no beneficial effects in stage III CRC. For stage IV CRC, the HR for OS in the RCT subgroup was 1.23 (95% CI 0.92–1.64) but only two RCTs were included. For non-RCT study, the combined HR for OS and DFS was 1.10 (95% CI 0.77–1.51) and 0.72 (95% CI 0.53–0.98), respectively, suggesting the beneficial effect for DFS and non-beneficial effect for OS. Conclusion For stage III CRC, MSI-H had no prognostic effect for OS, DFS, and DSS. For stage IV CRC, DFS showed a beneficial result, whereas OS did not; however, the included studies were limited and needed further exploration.

Sign in / Sign up

Export Citation Format

Share Document