A Guide to ASCO 2013: Key Targeted Trials

May 14, 2013
Anna Azvolinsky, PhD
Anna Azvolinsky, PhD

Volume 2, Issue 3

In advance of the 2013 American Society of Clinical Oncology annual meeting, Targeted Therapy News spoke with this year’s chair of the Scientific Program Committee, Douglas Yee, MD, about key presentations and sessions that attendees can expect.

Douglas Yee, MD

TTN: As the chair of the scientific committee for this year’s meeting, what are the new types of sessions for this upcoming year or new ways for clinicians and researchers to interact at the meeting?

TTN: Could you highlight the role of the pre-meeting session? This is a new addition to the annual meeting that started in 2012.

TTN: Translational medicine has been a major theme of the meeting and continues to be so for this year. Could you highlight how scientists and clinical researchers are collaborating and transferring information from the laboratory bench to the clinical setting and vice versa? Are there any sessions that will particularly highlight this communication?

TTN: As a breast cancer clinician and researcher, are there any clinical trial sessions or data that you are particularly looking forward to?

TTN: How will T-DM1, which has recently been approved for HER2-positive metastatic breast cancer, fit into the current treatment paradigm for HER2-positive cancer?

In advance of the 2013 American Society of Clinical Oncology (ASCO) annual meeting,Targeted Therapy Newsspoke with this year’s chair of the Scientific Program Committee, Douglas Yee, MD, about key presentations and sessions that attendees can expect.Yee:The one concept we tried last year at the meeting and expanded this year is post-plenary sessions. The plenary session is meant to highlight the highest- impact science submitted to ASCO, but to have a discussion with the presenter about what the results actually mean is difficult because of the thousands of people that attend the session. The post-plenary session is a way for the presenter and several discussants to really put a spotlight on the plenary session data. This is an opportunity for a presentation that is nonscripted and for viewers of the presentation to engage with the presenter and discussants. These sessions take place immediately after the plenary presentations.Yee:The premeeting has a few important sessions. There is a session on clinical trials with molecular selection of molecular biomarkers that is particularly relevant in this day and age. As targeted agents move forward in development, they likely work only in a select number of patients within a particular cancer type. In the context of molecular analysis, how do we design trials and develop therapies? The session is useful for anyone who wants a deep-dive into how to design biomarker-driven trials. TTN: What do you see as a challenge in coordinating and planning the meeting? Yee: The general challenge of ASCO has to do with the size and scope of the science. On one hand, it is an incredible meeting because there is such a broad representation of the latest that is going on in every facet of oncology clinical research and the science of oncology. But at the same time, it is such a big meeting that you don’t necessarily get to attend all of the venues you would like and interact with everyone you want to interact with. I think the program committee has been particularly conscious of this. We need big sessions to present the important data, but we also need smaller sessions to foster better interactions. At the same time, we also want to have sessions where experts in their field can really discuss what they think of new developments in clinical and basic science research.Yee:I think that is actually a challenge of the state of oncology in general. We now understand that there are specific molecular targets that are critical for tumor biology, and these molecular targets exist across broad types of tumors. We have drugs that have substantial activity in targeting specific tumor types, the HER2 targeted therapies in breast cancer, for example. At the same time, there are other drugs available with activity across many cancer types. New therapies that target the mTOR/PI3K pathway, for example, need to be discussed and understood in a deeper way. I think the educational sessions are particularly important for both of these scenarios. One of the [sessions] I think that members may not attend as much compared to other sessions are the developmental therapeutics sessions. In these sessions you can really begin to discuss ‘if we have an EGFR inhibitor and a PI3K inhibitor, how do we begin to put those together across different cancer types?’ I think for me that is the aspect of the meeting program that is particularly interesting; how do we use the infor- mation obtained from model systems to develop new therapeutics for cancer treatment? At the same time, anyone interested in a particular cancer type can stay on top of their specific field by attending the right sessions. This is what makes the meeting worthwhile— it is an opportunity for people to catch up on what they need to know.Yee:For someone trying to stay up to date on the breast cancer field, it is challenging to think about the HER2-positive subset of breast cancer because there are a lot of choices and it is not entirely clear how to best sequence the use of these new drugs. Therapies that target the estrogen receptor are also challenging because there are new therapies that can be used to target the estrogen receptor and other signaling pathways, like the mTOR inhibitors and the new investigational CDK4/6 antagonists, for example. The challenge is how to bring these new drugs into clinical practice, and, in meaningful clinical trials for women with advanced disease, how to control their disease with a goal of prolonging their overall survival and also impacting their quality of life in a positive way. At the same time, how do we take these strategies to the adjuvant setting to optimize their use when we know that not all patients will benefit from an mTOR inhibitor or the CDK4/6 inhibitor? New trials will begin to address this.Yee:I think T-DM1 is an incredibly interesting development, and this is coming from someone who is a laboratory-based researcher who is interested in the mechanisms of action of growth factor receptors and what they do biologically and how you target them. In many ways, T-DM1 represents something different. T-DM1 has shown us that without fully understanding how a target works biologically, we can use an antibody to bind to the target so that it internalizes a toxin attached to the antibody. So now we have to understand the linker chemistry, the linker between the toxin and the antibody, which is likely the key to how the molecule works or doesn’t work. This concept has been around for some time, but the successful use of this strategy on the scale of HER2-positive breast cancer is a very important advance. It represents another way to treat HER2-positive breast cancer that almost has nothing to do with the mechanism of action of HER2 in the tumor.

TTN: What are the sessions that you will be attending at the annual meeting this year?

Trial Data to Be Presented at ASCO 2013

  1. Colorectal cancer:KRAS/NRASandBRAFmutation status biomarker analysis in the phase 3 PRIME trial. Abstract #3511. A new, prospective biomarker analysis will be presented from the PRIME ‘203 trial of panitumumab plus FOLFOX versus FOLFOX as first-line treatment for wild-typeKRASmetastatic colorectal cancer (mCRC). Patient tumor samples were assessed for additionalRASmutations. The additional mutations inRASwere associated with an inferior progression-free survival and overall survival in the trial, according to the abstract.
  2. Breast cancer: A phase II randomized trial of lapatinib with either vinorelbine or capecitabine as first- and second-line therapy for HER2 overexpressing metastatic breast cancer (MBC). Abstract #516.
  3. Melanoma: OPTiM: a randomized phase 3 trial of talimogene laherparepvec (T-VEC) vs subcutaneous (SC) granulocyte-macrophage colony-stimulating factor (GM-CSF) for the treatment (tx) of unresected stage IIIB/C and IV melanoma. Abstract #LBA9008.
  4. Melanoma: Phase I combination results of nivolumab plus ipilimumab dose- escalation study in metastatic melanoma patients (NCT01024231). Abstract # pending.
  5. Ovarian cancer: Randomized, double-blind, phase III trial of pazopanib versus placebo in women who have not progressed after first line chemotherapy for advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer (AOC): Results of an international Intergroup trial (AGO-OVAR16). Abstract #LBA5503.
  6. Cervical cancer: Incorporation of bevacizumab in the treatment of recurrent and metastatic cervical cancer: A phase III randomized trial of the Gynecologic Oncology Group. Abstract #3. Results were made public in February 2013 when an interim analysis demonstrated that patients with advanced, recurrent, or persistent cervical cancer not curable with standard treatment who received bevacizumab lived 3.7 months longer than patients treated with chemotherapy alone. This is the first study to demonstrate that a targeted agent significantly improved overall survival in gynecologic cancer.
  7. Glioblastoma: Final results of the phase III CENTRIC Trial: cilengitide combined with standard treatment for patients with newly diagnosed glioblastoma with O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation. Abstract #LBA2009.
  8. Peripheral T-cell lymphoma: Results of the BELIEF registrational phase 2 trial: Belinostat, a novel pan-histone deacetylase inhibitor (HDACi), in relapsed or refractory peripheral T-cell lymphoma (R/R PTCL). Abstract #8507.

How T-DM1 fits into the treatment landscape is not certain and will require further investigation. I am part of the I-SPY 2 clinical trial [NCT01042379], which is bringing certain drugs into the neoadjuvant setting to treat breast cancer. We will be offering both pertuzumab and T-DM1 in the neoadjuvant setting for HER2-breast cancer. The advantage of the trial is that we take and analyze samples to develop biomarkers to predict response and resistance. Once we understand this—-which tumors benefit from T-DM1 or pertuzumab or trastuzumab or any combination—-we will be better able to individualize care for our patients. Right now, the correct sequence of therapies and for which patients with advanced cancer is not known. Since we don’t know this information, it will be a challenge to use these drugs in the adjuvant setting.Yee:One of the best parts of ASCO is attending sessions on topics you know very little about. I am very interested in the educational session on comparative effectiveness research in oncology. The idea is that we can learn from patients that are not enrolled in clinical trials to provide better care. I will also attend sessions on how preclinical research can best guide clinical trial design. I am very interested in the new immunotherapy developments. I am not an immunotherapist, but one thing that I have learned from attending many ASCO meetings is that you can learn quite a lot about a topic you may not know very well, and then think about how to apply the knowledge to your own clinical practice or research.

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