scholarly journals 432 3-year results of the phase 2 randomized trial for talimogene laherparepvec (T-VEC) neoadjuvant treatment plus surgery vs surgery in patients with resectable stage IIIB-IVM1a melanoma

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A458-A458
Author(s):  
Reinhard Dummer ◽  
David Gyorki ◽  
John Hyngstrom ◽  
Adam Berger ◽  
Robert Conry ◽  
...  
Keyword(s):  
Sensitivity Analysis ◽  
Neoadjuvant Treatment ◽  
Anticancer Therapy ◽  
Distant Recurrence ◽  
Advanced Melanoma ◽  
Stage Iiib ◽  
List Type ◽  
Talimogene Laherparepvec ◽  
Free Survival

BackgroundNeoadjuvant immunotherapies and targeted therapies for advanced melanoma are an active area of investigation. This is the first clinical trial of an approved oncolytic viral immunotherapy as a neoadjuvant treatment in advanced melanoma and the largest randomized controlled neoadjuvant trial including all types of resectable regional metastases to date. Previously published 2-year primary analysis results reported improved recurrence-free survival (RFS, HR 0.66, P=0.038) and overall survival (OS, HR 0.49, P=0.050) for neoadjuvant T-VEC plus surgery vs immediate surgery in resectable stage IIIB-IVM1a melanoma patients.1 Here, we report the 3-year interim analysis results.MethodsPatients with resectable stage IIIB-IVM1a melanoma and ≥ 1 injectable cutaneous, subcutaneous, or nodal lesions were randomized 1:1 to receive 6 doses/12 weeks of neoadjuvant T-VEC then surgery (Arm 1) vs immediate surgical resection (Arm 2). T-VEC was administered until surgery, no remaining injectable tumors, or intolerance. RFS was defined as time from randomization to the first of local, regional, or distant recurrence, or death, where patients who did not receive surgery were imputed as events at baseline. Key secondary and exploratory endpoints include safety, an RFS sensitivity analysis that censored events at the start of subsequent anticancer therapy, OS, and event-free survival (EFS), defined as time from randomization to disease progression that precludes surgery, or local, regional or distant recurrence post-surgery, or death from any cause, whichever occurs first. All P values are descriptive. NCT02211131.ResultsAs of April 30, 2020, median follow-up for all patients was 41.3 months. For Arm 1 vs. Arm 2, the 3-year KM estimates of RFS were 46.5% vs. 31.0% (HR 0.67, P=0.043). In the RFS sensitivity analysis that removed the potential effect of subsequent anticancer therapy on RFS, the 3-year Kaplan-Meier (KM) estimates of RFS were 49.1% for Arm 1 and 22.9% for Arm 2 (HR 0.60, P=0.022). The 3-year KM estimates of EFS were 50.3% for Arm 1 and 32.7% for Arm 2 (HR 0.58, P=0.015). For OS, the 3-year KM estimates were 83.2% for Arm 1 and 71.6% for Arm 2 (HR 0.54, P=0.061). No new safety signals were detected.ConclusionsAt 3-year follow up, we continued to observe improved RFS and OS and observed improved EFS with neoadjuvant T-VEC plus surgery compared with surgery alone. These results build upon the prior 2-year results to support the treatment effect of neoadjuvant T-VEC on advanced resectable melanoma. The final analysis will occur at 5 years.Acknowledgements• The authors thank the investigators, patients, and study staff who are contributing to this study.• The study was sponsored and funded by Amgen Inc. • Medical writing support was provided by Christopher Nosala (Amgen Inc.).Trial RegistrationNCT02211131Ethics ApprovalThe study was approved by all institutional ethics boards.ReferenceDummer R, Gyorki DE, Hyngstrom J, et al. Primary 2-year (yr) results of a phase II, multicenter, randomized, open-label trial of efficacy and safety for talimogene laherparepvec (T-VEC) neoadjuvant (neo) treatment (tx) plus surgery (surg) vs surg in patients (pts) with resectable stage IIIB-IVM1a melanoma. Ann Oncol 2019;30;V903.

One-year (yr) recurrence-free survival (RFS) from a randomized, open label phase II study of neoadjuvant (neo) talimogene laherparepvec (T-VEC) plus surgery (surgx) versus surgx for resectable stage IIIB-IVM1a melanoma (MEL).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 9520-9520 ◽  
Author(s):  
Reinhard Dummer ◽  
David E. Gyorki ◽  
John Robert Hyngstrom ◽  
Adam C. Berger ◽  
Robert Martin Conry ◽  
...  
Keyword(s):  
Sensitivity Analysis ◽  
Surgical Outcome ◽  
Distant Recurrence ◽  
Stage Iiib ◽  
Primary Analysis ◽  
Open Label ◽  
Free Survival ◽  
Open Label Phase ◽  
One Year

9520 Background: We previously reported that neo T-VEC + surgx resulted in a pathologic CR rate of 21% and an OR rate of 14.7% in a randomized trial of neo T-VEC + surgx vs upfront surgx in pts with resectable stage IIIB/C/IVM1a MEL (Andtbacka et al, ASCO 2018; NCT02211131). Here, we present results from an interim 1-yr analysis of RFS. Methods: Patients (pts) with resectable stage IIIB/C/IVM1a MEL, ≥ 1 injectable cutaneous, subcutaneous, or nodal lesions ≥ 10 mm, and no systemic tx 3 mos prior were randomized 1:1 to 6 doses/12 wks of T-VEC followed by surgx during wks 13-18 (Arm 1) vs upfront surgx during wks 1-6 (Arm 2). T-VEC was given at standard dosing until surgx, no injectable tumors, or intolerance. This analysis conducted on the ITT set estimated a between-group difference in 1-yr RFS per protocol. An RFS event was defined as the first of local, regional or distant recurrence or death due to any cause after surgx. Pts without a R0 surgical outcome or withdrew prior to surgx were considered an event at randomization for RFS. In a sensitivity analysis, RFS was calculated from randomization to the date of the first post-surgx event regardless of surgical outcome. Results: 150 pts were randomized (76 Arm 1, 74 Arm 2). Median (range) follow-up time was 20.6 (0.1, 38.5) mos in Arm 1 and 20.0 (0.1, 35.3) mos in Arm 2. 75% in Arm 1 and 93% in Arm 2 had surgx as planned. R0, R1, and R2 rates, respectively, for Arm 1 were 42.1%, 31.6%, and 1.3% and for Arm 2 were 37.8%, 51.4%, and 4.1%. At 1 yr, 33.5% of pts in Arm 1 and 21.9% of pts in Arm 2 remained recurrence free (HR 0.73, P= 0.048). From the sensitivity analysis, 55.8% of pts in Arm 1 and 39.3 % in Arm 2 remain recurrence free at 1 yr (HR 0.63, P= 0.024). OS rates at 1 yr were 95.9% in Arm 1 and 85.8% in Arm 2 (HR 0.47, P= 0.076). Pts receiving subsequent adjuvant tx was 8 (11%) in Arm 1 and 20 (29%) in Arm 2- most common was immunotherapy 6 (8.2%) and 8 (11.6%), respectively. Conclusions: In the largest randomized neo trial to date in resectable stage IIIB-IVM1a MEL, the following outcomes were improved with neo T-VEC monotherapy vs surgx: R0 surgical resections, 1-yr RFS, and OS. Primary analysis of RFS at 2 yrs is expected. Clinical trial information: NCT02211131.

429 Long-term analysis of MASTERKEY-265 phase 1b trial of talimogene laherparepvec (T-VEC) plus pembrolizumab in patients with unresectable stage IIIB-IVM1c melanoma

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A454-A454
Author(s):  
Georgina Long ◽  
Reinhard Dummer ◽  
Douglas Johnson ◽  
Olivier Michielin ◽  
Salvador Martin-Algarra ◽  
...  
Keyword(s):  
Pigment Cell ◽  
Objective Response ◽  
Stage Iiib ◽  
List Type ◽  
Talimogene Laherparepvec ◽  
Unresectable Stage ◽  
Long Term Follow Up ◽  
Phase 1B

BackgroundPrevious findings from the MASTERKEY-265 phase 1b study showed that the combination of T-VEC and pembrolizumab was well tolerated and produced a high complete response (CR) rate of 43% in patients with advanced melanoma.1 The 3-year progression-free survival (PFS) and overall survival (OS) rates at that time were 53.6% and 71%, respectively. Here, we report the results of the long-term follow-up efficacy analyses.MethodsThe MASTERKEY-265 phase 1b trial (NCT02263508) was an open-label, single-arm study that enrolled patients who had unresectable, stage IIIB-IVM1c melanoma with injectable, measurable lesions and no prior systemic treatment. T-VEC was administered intralesionally at the approved dosing starting day 1 of week 1. Pembrolizumab (200 mg) was administered intravenously Q2W beginning on day 1 of week 6. The maximum treatment period was 2 years. The primary endpoint was dose-limiting toxicities; key secondary endpoints included objective response rate and PFS per modified irRC, OS, and safety.ResultsAs of the data cutoff (Mar 2, 2020), all 21 patients enrolled were off treatment; 6 died and 15 are in long-term follow-up. The median follow-up time was 58.6 months (range: 1.4–61.6). The CR rate remained 43% (9/21 patients). Twelve of the 13 responders (92.3%) are still in response, including all 9 patients with a CR. Median duration of response was not reached (range: 2.8+–54.3+ months). Median PFS and OS were not reached at the data cutoff. KM estimates of 4-year PFS and OS rates were 55.9% and 71.4%, respectively, which have held stable since the 3-year analysis. Patients who achieved a CR or partial response had better OS (p=0.0056) compared to those who did not respond. Median OS for non-responders was 24.4 months and was not reached for responders. No additional safety signals were detected.ConclusionsAt almost 5 years of follow-up, median PFS and OS were not reached for patients treated with the combination of T-VEC and pembrolizumab in this phase 1b study of unresectable metastatic melanoma. 92% of responders remained in response with improved OS observed in responders compared with non-responders. The corresponding randomized phase 3 trial has completed enrollment and is currently ongoing.Trial RegistrationNCT02263508Ethics ApprovalThe study was approved by the Ethics Board of each institution involved in this study and can be produced upon request.ReferenceLong G, Dummer R, Andtbacka R, et al. Follow-up analysis of MASTERKEY-265 Phase 1b (ph1b) trial of talimogene laherparepvec (T-VEC) in combination (combo) with pembrolizumab (pembro) in patients (pts) with unresectable stage IIIB–IVM1c melanoma (MEL). Pigment Cell Melanoma Res 2019;32:133–134.

308 Indirect treatment comparison of nivolumab versus placebo as adjuvant treatment for melanoma

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A335-A335
Author(s):  
Jeffrey Weber ◽  
Paolo Ascierto ◽  
Mark Middleton ◽  
Delphine Hennicken ◽  
Roberto Zoffoli ◽  
...  
Keyword(s):  
Sensitivity Analysis ◽  
Lower Risk ◽  
Phase 3 ◽  
Free Survival ◽  
Intention To Treat ◽  
Risk Of Death ◽  
Link Type ◽  
Indirect Treatment ◽  
Resected Stage

BackgroundWe have previously performed indirect treatment comparisons (ITCs) to demonstrate improvements in recurrence-free survival (RFS) and distant metastasis-free survival with nivolumab versus placebo as adjuvant treatment for resected melanoma; however, overall survival (OS) data were not available at the time. Recently, results of the phase 3 CheckMate 238 trial in patients with resected stage IIIB–IIIC/IV melanoma (American Joint Committee on Cancer [AJCC], 7th edition) showed no statistically significant difference in OS between nivolumab and ipilimumab; however, OS events were fewer than expected. In the phase 3 EORTC 18071 trial in patients with resected stage IIIA–IIIC melanoma (AJCC, 6th edition), OS was improved with ipilimumab versus placebo. Here, we provide an update on RFS and an analysis of OS in ITCs of nivolumab and placebo using data from these 2 trials with a common comparator arm: ipilimumab 10 mg/kg.MethodsITCs of nivolumab versus placebo were conducted using 4-year minimum follow-up data from CheckMate 238 (NCT02388906) and 5.3-year median follow-up data from EORTC 18071 (NCT00636168). Bucher ITCs were performed to estimate RFS and OS in the intention-to-treat populations. A sensitivity analysis of OS adjusting for subsequent therapy options was conducted in 2 steps: (1) after controlling for possible confounders and assuming that the only difference was the effect of different subsequent therapies, postrecurrence survival was compared between the 2 ipilimumab arms in each study, and (2) after adjusting for differences in postrecurrence survival, ITCs of nivolumab versus adjusted placebo were performed.ResultsIn these ITC analyses, RFS and OS results with nivolumab suggested an improvement compared with placebo. In the intention-to-treat population, nivolumab was associated with a lower risk of recurrence or death (RFS HR, 0.55; 95% CI, 0.43–0.70) and a lower risk of death (OS HR, 0.62; 95% CI, 0.44–0.88) than placebo. In the sensitivity analysis, a 63% average increase in postrecurrence survival benefit was estimated with ipilimumab in CheckMate 238 compared with ipilimumab in EORTC 18071. After adjusting for this increase in both the ipilimumab and placebo arms in EORTC 18071, nivolumab was associated with a lower risk of death than placebo (OS HR, 0.65; 95% CI, 0.45–0.91), similar to the unadjusted analysis.ConclusionsDespite the changing treatment landscape and the increased number of therapeutic options for metastatic melanoma, these ITCs suggested clinically meaningful improvement in RFS and OS with adjuvant nivolumab compared with a wait-and-watch strategy in high-risk patients with resected melanoma.AcknowledgementsWriting and editorial assistance were provided by Kakoli Parai, PhD, and Andrea Lockett of Ashfield Healthcare Communications, funded by Bristol-Myers Squibb Company.Trial RegistrationNCT02388906 (CheckMate 238), NCT00636168 (EORTC 18071)

Adaptive Dosing of Nivolumab + Ipilimumab Immunotherapy Based Upon Early, Interim Radiographic Assessment in Advanced Melanoma (The ADAPT-IT Study)

2021 ◽  
Author(s):  
Michael A. Postow ◽  
Debra A. Goldman ◽  
Alexander N. Shoushtari ◽  
Allison Betof Warner ◽  
Margaret K. Callahan ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Progression Free Survival ◽  
Advanced Melanoma ◽  
Computed Tomography Scan ◽  
Free Survival ◽  
Immunotherapy Trial ◽  
Grade 3 ◽  
Almost All ◽  
Tomography Scan

PURPOSE Nivolumab + ipilimumab (nivo + ipi) is highly efficacious but has high toxicity. Standard treatment in advanced melanoma is four doses of nivo + ipi followed by nivo alone. Whether four doses of nivo + ipi are needed is unclear. METHODS The Adaptively Dosed ImmunoTherapy Trial (ADAPT-IT) study ( NCT03122522 ) is a multicenter, single-arm phase II clinical trial. Patients received two doses of nivo (1 mg/kg) + ipi (3 mg/kg) followed by a computed tomography scan at week 6. Patients without new lesions or index lesion tumor growth of > 4% had protocol-defined early favorable antitumor effect (FATE) and ceased nivo + ipi, transitioning to nivo monotherapy. Patients without FATE at week 6 received the standard third and fourth doses of nivo + ipi followed by nivo monotherapy. The primary end point was response rate by RECIST 1.1 at week 12. Secondary end points included additional efficacy assessments and safety. RESULTS Sixty patients were enrolled; 41 patients (68%) had FATE at week 6 and met criteria for stopping nivo + ipi. Best overall response rates by RECIST at week 12 or any time afterward were 48% (95% CI, 35 to 62) and 58% (95% CI, 45 to 71), respectively. With a median follow-up of 25 months, the estimated 18-month progression-free survival and overall survival are 52% and 80%, respectively. Fifty seven percent of patients had grade 3-5 treatment-related toxicity. CONCLUSION The efficacy and toxicity of standard four dose nivo + ipi induction therapy in melanoma is likely driven by the first two doses. An interim computed tomography scan after two doses guided cessation of combination dosing and identified almost all responders. Longer follow-up and further study are needed to fully understand the implications of a shortened induction course of nivo + ipi.

Retreatment with talimogene laherparepvec for advanced melanoma

Immunotherapy ◽  
2020 ◽  
Vol 12 (16) ◽  
pp. 1167-1172
Author(s):  
Janice Hu ◽  
Sabran J Masoud ◽  
Surya Ravichandran ◽  
Georgia M Beasley ◽  
Paul J Mosca
Keyword(s):  
Adverse Event ◽  
Disease Progression ◽  
Initial Treatment ◽  
Relevant Literature ◽  
Complete Response ◽  
Advanced Melanoma ◽  
Severe Adverse Event ◽  
Stage Iiib ◽  
Talimogene Laherparepvec ◽  
Mixed Response

Aim: Talimogene laherparepvec (T-VEC) is a genetically modified oncolytic herpesvirus approved for the treatment of unresectable, locoregionally advanced and recurrent melanoma. There is little relevant literature in the context of retreatment with T-VEC. Materials & methods: We reviewed four patients aged 71–87 years old with stage IIIB–IV melanoma at treatment who were rechallenged with T-VEC after experiencing recurrence of locoregional disease or prior treatment-limiting toxicity. Results: Cessation of initial treatment was due to one of the following reasons: severe adverse event (one case), mixed response (one case) or complete response (two cases). Three males and one female underwent T-VEC retreatment with a mean of 5.5 injection cycles. Three patients experienced a complete response to retreatment, while one experienced disease progression. Conclusion: Intralesional T-VEC may be effective and well-tolerated in patients who have completed prior T-VEC therapy.

QTWIST analysis in the RECOURSE trial.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 698-698 ◽  
Author(s):  
Josep Tabernero ◽  
Eric Van Cutsem ◽  
Atsushi Ohtsu ◽  
Nadia Amellal ◽  
Stéphanie Cadour ◽  
...  
Keyword(s):  
Sensitivity Analysis ◽  
Adverse Events ◽  
Progression Free Survival ◽  
Health State ◽  
Free Survival ◽  
Utility Coefficient ◽  
Grade 3 ◽  
Overall Survival Benefit

698 Background: RECOURSE showed that treatment with trifluridine/tipiracil in patients in patients (pts) with refractory metastatic colorectal cancer was associated with significantly improved survival vs placebo. As quality of life (QoL) was not captured in the trial, other methods were used to evaluate potential impact on QoL. Methods: We used the QTWIST method, i.e. quality-adjusted TWIST (time without symptoms of disease or toxicity), to explore survival adjusted for QoL with trifluridine/tipiracil vs placebo in the RECOURSE population. QTWIST incorporates a trade-off between time spent with treatment-related adverse events versus improvement in progression-free survival, and combines an estimate of the mean duration of each health state (TOX, TWIST, and RELAPSE [REL]), weighted by a utility coefficient, into a global QTWIST score. TOX represents time with grade 3/4 treatment-related adverse events that are expected to impact QoL (i.e. nausea, vomiting, diarrhea, fatigue/asthenia, anorexia, febrile neutropenia) before progression, TWIST represents time without symptoms or toxicity; and REL represents time from progression (as defined in the RECOURSE trial) until death. We applied a utility coefficient of 1 for TWIST and values of 0.5 for TOX and REL. A sensitivity analysis varied the utility coefficients for TOX and REL from 0 to 1. Results: 798 pts (533 trifluridine/tipiracil vs 265 placebo) were included with median follow-up time of 11.8 mo. The between-group difference in the global QTWIST score was 1.5 mo (95% CI, 1.49–1.52) in favor of trifluridine/tipiracil. Using varying utility coefficients for TOX and REL from 0 to 1 as a sensitivity analysis, the between-group difference in the global QTWIST score ranged from 1.3 to 1.7 mo, always in favor of trifluridine/tipiracil. Conclusions: The median overall survival benefit observed with trifluridine/tipiracil vs placebo in RECOURSE was 1.8 months. Consistently, patients' QoL as evaluated by QTWIST showed that quality-adjusted survival with Lonsurf is significantly improved by 1.5 months vs placebo. Clinical trial information: NCT01607957. [Table: see text]

A phase Ib clinical trial of neoadjuvant OrienX010, an oncolytic virus, in combination with toripalimab in patients with resectable stage IIIb to stage IVM1a acral melanoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9570-9570
Author(s):  
Xuan Wang ◽  
Chuanliang Cui ◽  
Lu Si ◽  
Caili Li ◽  
Jie Dai ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Oncolytic Virus ◽  
Response Rate ◽  
Checkpoint Inhibitors ◽  
Neoadjuvant Treatment ◽  
Stage Iiib ◽  
Recurrence Free Survival ◽  
Free Survival ◽  
Phase Ib ◽  
Acral Melanoma

9570 Background: Metastatic acral melanoma is very difficult to treat. Unlike cutaneous melanoma, acral melanoma responds poorly to checkpoint inhibitors in monotherapy. OrienX010 is a granulocyte-macrophage colony-stimulating factor expressing herpes simplex type-1 derived oncolytic virus. It has shown robust efficacy in metastatic acral melanoma, and may improve the response to checkpoint inhibitors. To evaluate the role of OrienX010 in combination with checkpoint inhibitors in acral melanoma, we conducted a Phase Ib neoadjuvant trial of OrienX010 in combination with the anti-PD-1 monoclonal antibody toripalimab in resectable stage IIIB-IVM1a acral melanoma (NCT04197882). Methods: Patients with resectable stage IIIB-IV M1a acral melanoma received neoadjuvant intratumoral OrienX010 up to 10 mL of 8 x 107 pfu/mL and intravenous toripalimab 3 mg/kg every 2 weeks for 4 – 6 doses prior to surgical resection. After resection, adjuvant toripalimab 3 mg/kg was administered every 3 weeks for up to 1 year. The primary endpoints were radiographic response rate per RECIST 1.1 and pathological response rate (pCR and pPR). The secondary endpoints were 1- and 2-year recurrence-free survival, and safety. Results: Between July 2019 and Jan 2021, 30 patients with regional metastatic acral melanoma were enrolled. Median age was 56.5 years, 14 (47%) were male, 19 (63%) had recurrent disease, and stage IIIB 12 (40%), IIIC 14 (47%), and IVM1a 4 (13%). Median tumor burden was 28mm (range, 10-80mm), and only 5 (17%) patients had melanoma mutations (2 cKIT, 1 NRAS, 2 BRAF). To date, of 24 patients who completed neoadjuvant treatment, 21 (88%) underwent surgery. Three (12%) patients did not undergo surgery due to disease progression prior to surgery and 6 patients are still receiving neoadjuvant treatment. Radiographic responses were seen in 10 (33%) patients. However, 17 of 21 (81%) patients showed pathologic responses in resected metastases, with 3 (14%) showing a pCR and 14 (67%) a pPR. Pathologic responses were associated with greater lymphoid infiltrate, hyaline fibrosis, and decrease in Ki-67 expression in the metastasis. At a median follow-up of 8.9 months, none of the patients who underwent resection have recurred. The neoadjuvant treatment was well tolerated, with all patients experiencing at least 1 treatment related adverse event (TRAE) and Grade 1 fever was most common. Three (10%) patients had a grade 3-4 TRAE, including 1 alanine aminotransferase increase and 2 wound infections. Conclusions: Neoadjuvant treatment with OrienX010 and toripalimab in resectable stage IIIB-IVM1a acral melanoma was well tolerated and produced a high pathologic response rate. To date, no patients have recurred, and recurrence-free survival evaluation is ongoing. This combination therapy warrants further evaluation in acral melanoma. Clinical trial information: NCT04197882.

Prognostic Indicators and Survival in Patients With Stage IIIB Inflammatory Breast Carcinoma After Dose-Intense Chemotherapy

2004 ◽  
Vol 22 (10) ◽  
pp. 1839-1848 ◽  
Author(s):  
George Somlo ◽  
Paul Frankel ◽  
Warren Chow ◽  
Lucille Leong ◽  
Kim Margolin ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Radiation Therapy ◽  
Stage Iiib ◽  
Prognostic Indicators ◽  
Related Factors ◽  
Free Survival ◽  
Axillary Nodes ◽  
Conventional Dose ◽  
Single Versus

Purpose To improve treatment outcome for patients presenting with inflammatory breast cancer (IBC), we have sequentially developed and tested single and tandem dose-intense chemotherapy regimens (DICT). Tumor- and treatment-related factors were analyzed to generate a prognostic model. Patients and Methods Between May 1989 and April 2002, 120 patients received conventional-dose chemotherapy, surgery, and sequentially developed single- or tandem-cycle DICT. Disease- and treatment-specific features were subjected to univariate and multivariate analysis to correlate with outcome. Results At a median follow-up of 61 months (range, 21 to 161 months), estimated 5-year relapse-free survival (RFS) and overall survival (OS) were 44% (95% CI, 34% to 53%) and 64% (95% CI, 55% to 73%), respectively. In an age-adjusted multivariate analysis, RFS was better in patients with estrogen receptor (ER)/progesterone receptor (PR)–positive tumors (P = .002), for patients with fewer than four involved axillary nodes before DICT (P = .01), and in patients treated with radiation therapy (P = .001) and tandem DICT (P = .049). OS was improved in patients with ER/PR-positive tumors (P = .002), in those with fewer than four involved axillary nodes before DICT (P = .03), and in patients treated with radiation therapy (P = .002). Conclusion This retrospective analysis suggests that either single or tandem DICT can be administered safely and may benefit selected patients with stage IIIB IBC. Those with receptor-negative IBC and with four or more involved axillary nodes before DICT need improved neoadjuvant and postadjuvant intensification therapy. A prospective randomized trial of single versus tandem DICT would be required to confirm the potential benefit of tandem DICT in the setting of IBC.

scholarly journals Evaluation of Two Dosing Regimens for Nivolumab in Combination With Ipilimumab in Patients With Advanced Melanoma: Results From the Phase IIIb/IV CheckMate 511 Trial

2019 ◽  
Vol 37 (11) ◽  
pp. 867-875 ◽  
Author(s):  
Celeste Lebbé ◽  
Nicolas Meyer ◽  
Laurent Mortier ◽  
Ivan Marquez-Rodas ◽  
Caroline Robert ◽  
...  
Keyword(s):  
Overall Survival ◽  
Response Rate ◽  
Objective Response ◽  
Progression Free Survival ◽  
Advanced Melanoma ◽  
Free Survival ◽  
End Point ◽  
Phase Iiib ◽  
Grade 3

PURPOSE Nivolumab 1 mg/kg plus ipilimumab 3 mg/kg (NIVO1+IPI3) is approved for first-line treatment of patients with advanced melanoma in several countries. We conducted a phase IIIb/IV study (CheckMate 511) to determine if nivolumab 3 mg/kg plus ipilimumab 1 mg/kg (NIVO3+IPI1) improves the safety profile of the combination. PATIENTS AND METHODS Patients (N = 360) age 18 years or older with previously untreated, unresectable stage III or IV melanoma were randomly assigned 1:1 to NIVO3+IPI1 or NIVO1+IPI3 once every 3 weeks for four doses. After 6 weeks, all patients received NIVO 480 mg once every 4 weeks until disease progression or unacceptable toxicity. The primary end point was a comparison of the incidence of treatment-related grade 3 to 5 adverse events (AEs) between groups. Secondary end points included descriptive analyses of objective response rate, progression-free survival, and overall survival. The study was not designed to formally demonstrate noninferiority of NIVO3+IPI1 to NIVO1+IPI3 for efficacy end points. RESULTS At a minimum follow-up of 12 months, incidence of treatment-related grade 3 to 5 AEs was 34% with NIVO3+IPI1 versus 48% with NIVO1+IPI3 ( P = .006). In descriptive analyses, objective response rate was 45.6% in the NIVO3+IPI1 group and 50.6% in the NIVO1+IPI3 group, with complete responses in 15.0% and 13.5% of patients, respectively. Median progression-free survival was 9.9 months in the NIVO3+IPI1 group and 8.9 months in the NIVO1+IPI3 group. Median overall survival was not reached in either group. CONCLUSION The CheckMate 511 study met its primary end point, demonstrating a significantly lower incidence of treatment-related grade 3-5 AEs with NIVO3+IPI1 versus NIVO1+IPI3. Descriptive analyses showed that there were no meaningful differences between the groups for any efficacy end point, although longer follow up may help to better characterize efficacy outcomes.

Sign in / Sign up

Export Citation Format

Share Document