Kantar Health, a leading global oncology consultancy, has identified several pivotal clinical trials that will be presented at the upcoming American Society of Clinical Oncology (ASCO) conference, which have the potential to significantly alter the treatment paradigm in several tumor types. A brief synopsis of some of those trials and an evaluation of the data expectations are discussed. For a full discussion of all 9 top picks, please see the associated article in the May issue of OBR Green.
Zytiga (abiraterone acetate, Janssen Biotech/Johnson & Johnson) plus Prednisone in Chemotherapy-naïve Castration Resistant Prostate Cancer (CPRC)
A mere four months after its approval in April 2011, Zytiga had captured approximately one-quarter of the patient share in the second-line CRPC market (Kantar Health, CancerMPact® Treatment Architecture 2011), and utilization continues to grow. The COU-AA-302, an international Phase 3 study, aims to move Zytiga into first-line. The study compares Zytiga plus prednisone with placebo plus prednisone in 1,088 asymptomatic or minimally symptomatic, chemotherapy-naive CRPC patients. In March, Janssen announced that the Independent Data Monitoring Committee (IDMC) unanimously recommended unblinding the study and offering Zytiga to patients in the placebo arm. While news of early unblinding is very promising, the subsequent patient cross-over may ultimately confound OS which could hamper the approval process down the road if a strong enough signal wasn’t already evident at the interim analysis. COU-AA-302, Abstract LBA4518, Saturday, June 2, 8:00 am
T-DM1 (Trastuzumab emtansine, Genentech/Roche) in HER2+ Breast Cancer
The concept behind T-DM1 is exciting – adding the benefit of chemotherapy to the specificity of targeted therapy, thereby decreasing normal chemotherapy-associated toxicities – which could lead to treatment paradigm changes if successful. Currently, three Phase 3 trials are examining the efficacy and safety of T-DM1 in first-line (MARIANNE), second-line (EMILIA), and third line (TH3RESA), of which EMILIA is expected to support initial launch. In March 2012, Genentech announced top-line results from the EMILIA trial, indicating improved PFS in patients treated with T-DM1 compared with those treated with Tykerb [lapatinib; GlaxoSmithKline] plus Xeloda [capecitabine; Roche] in 991 HER2+ breast cancer patients who had previously received treatment with Herceptin and a taxane.
Last years’ FDA revocation of Avastin’s [bevacizumab; Genentech/Roche] approval in breast cancer has raised awareness about the need for meaningful PFS or OS benefits in this disease. With this in mind, all eyes are going to be on the magnitude of PFS benefit produced in EMILIA, especially considering that any overall survival (OS) data presented at ASCO will be immature. EMILIA, Abstract LBA1, Sunday June 3, 1:45pm, Plenary
Dabrafenib [GSK2118436; GlaxoSmithKline] and Trametinib [GlaxoSmithKline] in First- Second-line, B-Raf Mutant, Metastatic Melanoma
Like ASCO 2011, ASCO 2012 is an exciting year for melanoma. GSK is presenting the results of two of their pipeline drugs, the B-Raf inhibitor dabrafenib and the MEK inhibitor trametinib.. In January 2011, GSK initiated a phase III trial (BREAK-3) to evaluate dabrafenib versus dacarbazine in 249 previously untreated Stage III/IV melanoma patients harboring BRAF V600E mutation. The fact that this trial is reporting out less than 18 months after initiation speaks to the enthusiasm of the melanoma community for targeted agents, something which didn’t exist 2 years ago, prior to the development of Yervoy [ipilimumab; Bristol-Myers Squibb] and Zelboraf [vemurafenib; Genentech/Roche].
This new found enthusiasm also includes increasing interest in MEK inhibitors, and GSK’s trametinib is the front-runner in development. In February, GSK announced that the Phase 3 METRIC study in 297 patients with advanced melanoma harboring a BRAF V600E/K mutation met the primary endpoint of prolonging PFS compared with chemotherapy. Details on the magnitude of benefit were not disclosed; and there had been speculation that MEK inhibitors would not be very efficacious as monotherapies, so the press release announcing positive results in METRIC is a welcome surprise.
In order for dabrafenib or trametinib to compete in the marketplace they will need to improve on impressive benchmarks set by Zelboraf — the BRIM3 trial showed 48% ORR, 5.3 month PFS, and 84% six-month OS — and/or show decreased levels of drug resistance or improved safety. If the monotherapies demonstrate lackluster efficacy, dabrefenib and trametnib could have a future in combination with each other — GSK is testing this combination in BRAF mutant metastatic melanoma patients; however this development is still in Phase II (to learn more stay after the METRIC presentation for Abstract 8510). BREAK-3, Abstract LBA8500, Monday, June 4, 8:00 am; METRIC, Abstract LBA8509, Monday, June 4, 3:15 pm
Of interest: updated OS results for Zelboraf in the BRIM3 trial a mere 15 minutes after the BREAK-3 presentation, at 8:30 am
These and other picks are outlined in the table below.
|Kantar Health’s Top Presentations of Interest, ASCO 2012|
|Agent||Indication||Abstract||Date and Time|
|Tivozanib||RCC, first-/second-line||4501||Saturday, 3:15pm|
|Avastin||Ovarian Cancer, platinum-resistant||LBA5002||Saturday, 3:30pm|
|Avastin||CRC, second-line||CRA3503||Sunday, 10:45am|
|T-DM1||HER2+ Breast Cancer, refractory||LBA1||Sunday, 1:45pm|
|Dabrafenib||Melanoma, first-line, B-RAF mutants||LBA8500||Monday, 8:00am|
|Trametinib||Melanoma, first-line, B-RAF mutants||LBA8509||Monday, 3:15pm|
|Cabozantinib||Thyroid Cancer, Medullary||5508||Monday, 11:30am|
|Afatinib||NSCLC, first-line, EGFR mutant||LBA7500||Monday, 3:00pm|
Following the 2012 ASCO meeting, Kantar Health will publish an article in Oncology Business Review to provide a synopsis of some of the most interesting next-generation agents and therapeutic approaches in development.
By Mara Jeffress, Associate Consultant, CancerMPact®, Kantar Health