Abstract 2233
Background
In a pooled analysis of COMBI-d (NCT01584648) and COMBI-v (NCT01597908) trials, D+T led to long-term disease control in many pts and 5-y survival in approximately one-third of pts with BRAF V600–mutant unresectable or metastatic melanoma. In pts with resected BRAF V600–mutant stage III melanoma in COMBI-AD (NCT01682083), adjuvant D+T significantly improved relapse-free survival (RFS) with 3- and 4- year RFS rates of 59% and 54%, respectively. A higher rate of permanent discontinuation due to AEs was observed in the adjuvant setting in COMBI-AD (26%) than in the metastatic setting in COMBI-d/v (15%).
Methods
Analyses were performed using pt-level pooled data from COMBI-d and COMBI-v (phase III randomized trials comparing D+T with D+ placebo [PBO] or vemurafenib in unresectable or metastatic BRAF-mutant melanoma) and COMBI-AD (phase III, randomized, double-blind, PBO-controlled trial comparing adjuvant D+T with PBO in resectable stage III melanoma). In COMBI-d/v, pts were treated until disease progression; in COMBI-AD, pts were treated for 12 mo with adjuvant D+T. AEs were graded using CTCAE v4.0 and assessed over time using exposure-adjusted rates (occurrences/pt/3-mo exposure) calculated over 3-mo intervals.
Results
All-cause AE rates were 98% (548/559) in the metastatic and 97% (422/435) in the adjuvant setting. Grade (G) ≥ 3 AE rates were 57% (319/559) in COMBI-d/v and 41% (180/435) in COMBI-AD. Pyrexia was the most common AE in COMBI-d/v (any-grade [58%]; G ≥ 3 [6%]) and COMBI-AD (any-grade [63%]; G ≥ 3 [5%]). There were no treatment (tx)-related deaths in COMBI-d/v or COMBI-AD. In the first 3 mo of tx, the exposure-adjusted AE rates for any event in pts treated with D+T in the metastatic and adjuvant setting were 7.54 and 6.14, respectively. AE rates decreased with increased time on tx: 3 to < 6 mo (3.93 [COMBI-d/v]; 2.58 [COMBI-AD]); 6 to < 9 mo (3.22; 1.80); and 9 to < 12 mo (2.94; 1.65).
Conclusions
In the metastatic and adjuvant settings, there was a trend toward decreased AEs with longer tx duration. The rate of G ≥ 3 AEs was lower in the adjuvant vs metastatic setting suggesting that increased AE-related discontinuations in COMBI-AD are unlikely due to excess toxicity.
Clinical trial identification
NCT01584648 NCT01597908 NCT01682083.
Editorial acknowledgement
Allison Lytle, PhD, from ArticulateScience LLC, funded by Novartis Pharmaceuticals Corporation.
Legal entity responsible for the study
Novartis Pharmaceuticals Corporation.
Funding
Novartis Pharmaceuticals Corporation.
Disclosure
J.J. Grob: Non-remunerated activity/ies, Medical writing assistance: ArticulateScience LLC; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pierre Fabre; Honoraria (self), Advisory / Consultancy: Sanofi; Honoraria (self), Advisory / Consultancy: Merck; Honoraria (self), Advisory / Consultancy: Pfizer. V.G. Atkinson: Non-remunerated activity/ies, Medical writing assistance: ArticulateScience LLC; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck Sharp & Dohme; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck Serono; Honoraria (self), Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Speaker Bureau / Expert testimony: Roche/Genentech; Travel / Accommodation / Expenses: OncoSec. C. Robert: Non-remunerated activity/ies, Medical writing assistance: ArticulateScience LLC; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Roche; Advisory / Consultancy: MSD; Advisory / Consultancy: Novartis; Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy: Array; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Merck. D. Schadendorf: Non-remunerated activity/ies, Medical writing assistance: ArticulateScience LLC; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche/Genentech; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck Sharp & Dohme; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Merck Serono; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Amgen; Honoraria (self), Advisory / Consultancy: Immunocore; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Incyte; Honoraria (self), Advisory / Consultancy: 4SC; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Pierre Fabre; Advisory / Consultancy: Mologen; Advisory / Consultancy: Sanofi/Regeneron; Speaker Bureau / Expert testimony: Roche; Travel / Accommodation / Expenses: Merck; Honoraria (self): Sysmex; Honoraria (self): Grünenthal Group; Honoraria (self): Agenus; Honoraria (self): Array BioPharma; Honoraria (self): AstraZeneca; Honoraria (self): LEO Pharma; Honoraria (self): Pfizer; Honoraria (self): Philogen; Honoraria (self): Regeneron; Honoraria (self): Mologen. P. Nathan: Non-remunerated activity/ies, Medical writing assistance: ArticulateScience LLC; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy: Immuncore; Advisory / Consultancy, Research grant / Funding (self): Pfizer; Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Advisory / Consultancy: GlaxoSmithKline; Advisory / Consultancy: Ipsen; Advisory / Consultancy: Merck. M.A. Davies: Non-remunerated activity/ies, Medical writing assistance: ArticulateScience LLC; Advisory / Consultancy, Research grant / Funding (self): GlaxoSmithKline; Advisory / Consultancy, Research grant / Funding (self): Genentech/Roche; Advisory / Consultancy: Novartis; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Vaccinex; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Syndax; Advisory / Consultancy: NanoString Technologies; Advisory / Consultancy: Array BioPharma; Research grant / Funding (self): AstraZeneca; Research grant / Funding (self): Merck; Research grant / Funding (self): Oncothyreon; Research grant / Funding (self): Myriad Genetics; Research grant / Funding (self): Sanofi. R. Kefford: Non-remunerated activity/ies, Medical writing assistance: ArticulateScience LLC; Advisory / Consultancy, Travel / Accommodation / Expenses: Amgen; Advisory / Consultancy: TEVA; Travel / Accommodation / Expenses: Bristol-Myers Squibb. R. Dummer: Non-remunerated activity/ies, Medical writing assistance: ArticulateScience LLC; Advisory / Consultancy, Intermittent, project focused : Novartis; Advisory / Consultancy, Intermittent, project focused : Merck Sharp & Dhome; Advisory / Consultancy, Intermittent, project focused : Bristol-Myers Squibb; Advisory / Consultancy, Intermittent, project focused : Roche; Advisory / Consultancy, Intermittent, project focused : Amgen; Advisory / Consultancy, Intermittent, project focused : Takeda; Advisory / Consultancy, Intermittent, project focused : Pierre Fabre; Advisory / Consultancy, Intermittent, project focused : Sun Pharma; Advisory / Consultancy, Intermittent, project focused : Sanofi; Advisory / Consultancy, Intermittent, project focused: Catalym . J.M. Kirkwood: Non-remunerated activity/ies, Medical writing assistance: ArticulateScience LLC; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Novartis; Advisory / Consultancy: Array BioPharma; Advisory / Consultancy, Research grant / Funding (institution): Immunocore; Advisory / Consultancy: Iovance; Advisory / Consultancy: Elsevier; Advisory / Consultancy: Checkmate Pharmaceuticals; Advisory / Consultancy, Research grant / Funding (institution): Merck; Research grant / Funding (institution): Prometheus Laboratories. K.T. Flaherty: Non-remunerated activity/ies, Medical writing assistance: ArticulateScience LLC; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: Genentech; Advisory / Consultancy: Merck; Advisory / Consultancy: Lilly; Advisory / Consultancy: Amgen; Advisory / Consultancy, Research grant / Funding (institution): Sanofi; Advisory / Consultancy, Shareholder / Stockholder / Stock options: Oncoceutics; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Adaptimmune; Advisory / Consultancy: Aeglea Biotherapeutics; Advisory / Consultancy, Shareholder / Stockholder / Stock options: Loxo; Advisory / Consultancy: Roche; Advisory / Consultancy: Asana Biosciences; Advisory / Consultancy: Incyte; Advisory / Consultancy, Shareholder / Stockholder / Stock options: Shattuck Labs; Advisory / Consultancy: Tolero Pharmaceuticals; Advisory / Consultancy: Array BioPharma; Advisory / Consultancy, Shareholder / Stockholder / Stock options: FOGPharma; Advisory / Consultancy: Neon Therapeutics; Advisory / Consultancy, Shareholder / Stockholder / Stock options: Tvardi; Advisory / Consultancy: Takeda; Advisory / Consultancy: Verastem; Advisory / Consultancy: Boston Biomedical; Advisory / Consultancy, Travel / Accommodation / Expenses: Pierre Fabre; Advisory / Consultancy: Cell Medica; Advisory / Consultancy, Travel / Accommodation / Expenses: Debiopharm Group; Shareholder / Stockholder / Stock options: Clovis Oncology; Shareholder / Stockholder / Stock options: X4 Pharma; Shareholder / Stockholder / Stock options: Strata Oncology; Shareholder / Stockholder / Stock options: PIC Therapeutics; Shareholder / Stockholder / Stock options: Fount Therapeutics; Shareholder / Stockholder / Stock options: Apricity Health; Shareholder / Stockholder / Stock options: Vivid Biosciences; Shareholder / Stockholder / Stock options: Checkmate Pharmaceuticals. A. Ribas: Non-remunerated activity/ies, Medical writing assistance: ArticulateScience LLC; Advisory / Consultancy: Merck; Advisory / Consultancy: Amgen; Advisory / Consultancy: Novartis; Advisory / Consultancy: Chugai Pharma; Shareholder / Stockholder / Stock options: Compugen; Shareholder / Stockholder / Stock options: FLX Bio; Shareholder / Stockholder / Stock options: CytomX Therapeutics; Shareholder / Stockholder / Stock options: Five Prime Therapeutics; Shareholder / Stockholder / Stock options: Advaxis; Shareholder / Stockholder / Stock options: Arcus Biosciences; Shareholder / Stockholder / Stock options: Tango Therapeutics; Shareholder / Stockholder / Stock options: PACT Pharma; Shareholder / Stockholder / Stock options: Merus; Shareholder / Stockholder / Stock options: Rgenix; Shareholder / Stockholder / Stock options: ImaginAb; Shareholder / Stockholder / Stock options: Lutris. P. Burgess: Non-remunerated activity/ies, Medical writing assistance: ArticulateScience LLC; Full / Part-time employment: Novartis; Shareholder / Stockholder / Stock options: GlaxoSmithKline. E. Gasal: Non-remunerated activity/ies, Medical writing assistance: ArticulateScience LLC; Shareholder / Stockholder / Stock options, Full / Part-time employment: Novartis. G.V. Long: Non-remunerated activity/ies, Medical writing assistance: ArticulateScience LLC; Honoraria (self), Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Roche/Genentech; Advisory / Consultancy: Amgen; Honoraria (self), Advisory / Consultancy: MERCK; Honoraria (self), Advisory / Consultancy: Novartis; Advisory / Consultancy: Array BioPharma; Advisory / Consultancy: Pierre Fabre.A. Hauschild: Non-remunerated activity/ies, Medical writing assistance: ArticulateScience LLC; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Amgen; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (institution): MerckSerono; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): MSD/Merck; Advisory / Consultancy, Research grant / Funding (institution): Philogen; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Pierre Fabre; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Provectus; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Regeneron; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy: OncoSec; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Sanofi-Genzyme; Advisory / Consultancy: Sun Pharma; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Novartis Pharma.
Resources from the same session
3628 - Predictive model for survival in advanced non-small-cell lung cancer (NSCLC) treated with frontline pembrolizumab
Presenter: Xabier Mielgo Rubio
Session: Poster Display session 3
Resources:
Abstract
5705 - External validation and longitudinal extension of the LIPI (Lung Immune Prognostic Index) for immunotherapy outcomes in advanced non-small cell lung cancer.
Presenter: Jakob Riedl
Session: Poster Display session 3
Resources:
Abstract
5758 - Changes of TCR Repertoire in Metastatic Renal Cell Carcinoma and Metastatic Melanoma Patients Treated with Nivolumab
Presenter: Martin Klabusay
Session: Poster Display session 3
Resources:
Abstract
1743 - Expression of MHC class I, HLA-A and HLA-B identifies immune activated breast tumors with favorable outcome
Presenter: María Del Mar Noblejas López
Session: Poster Display session 3
Resources:
Abstract
2219 - Prognostic Significance of Tumor Tissue NeuGcGM3 Ganglioside Expression and Predictive Value of Circulating Tumor Cell Count Monitoring in Patients Receiving Racotumomab Immunotherapy
Presenter: Necdet Üskent
Session: Poster Display session 3
Resources:
Abstract
2996 - Evolution of Myeloid-Derived Suppressor Cells and Objective Response Rate in Relapsed/Refractory Diffuse Large B Cell Lymphoma (R/R DLBCL) patients after receiving immunotherapy
Presenter: Carlos Jiménez Cortegana
Session: Poster Display session 3
Resources:
Abstract
2110 - A Phase Ia/Ib trial of the anti-programmed death-ligand 1 (PD-L1) human monoclonal antibody (mAb), CS1001, in patients (pts) with advanced solid tumors or lymphomas
Presenter: Lin Shen
Session: Poster Display session 3
Resources:
Abstract
3515 - Results from a randomised Phase 1/2 trial evaluating the safety and antitumour activity of anti-PD-1 (MEDI0680)/anti-PD-L1 (durvalumab) vs anti-PD-1 (nivolumab) alone in metastatic clear cell renal cell carcinoma (ccRCC)
Presenter: Martin Voss
Session: Poster Display session 3
Resources:
Abstract
3566 - Pembrolizumab in Advanced Rare Cancers
Presenter: Aung Naing
Session: Poster Display session 3
Resources:
Abstract
3567 - High clinical benefit rates of pembrolizumab in very rare sarcoma histotypes: first results of the AcSé Pembrolizumab study
Presenter: Jean-Yves Blay
Session: Poster Display session 3
Resources:
Abstract