Conference Reports
44th ASCO Annual Meeting
Chicago, IL, 30th May – 3rd June 2008
Chicago’s vast McCormick Place once again played host to the American Society of Clinical Oncology Annual meeting. With over 35,000 attendees, this year’s poster, symposia and education sessions were set to be better than ever.
Over 450 attendees
from 315 companies
were welcomed for
two days of leadership
sessions and
company presentations
by Robert Lee
Kilpatrick, a partner of
the meeting’s hosts
Technology Vision
Group and Matt Gardner,
CEO of co-hosts
BayBio. Kelly Slone,
Director of the Medical
Industry Group,
extended the welcome and provided some context for the
deal-making and financing that was to follow with the fact
that 30% of all venture capital investment is in the life sciences
business.
It is estimated that in 2008, approximately 1,437,180 new cancer cases will be diagnosed in the US, and cancer will claim the lives of an estimated 565,650 people. Cancer death rates have been decreasing steadily over the last 15 years, in part due to better diagnosis, superior understanding of the subject and of course, better treatment strategies. The ASCO foundation aids both oncologists and patients by supporting the development of a c c u rate, physi cianapproved cancer information.
Once again the 'blockbusters' dominated the meeting with a multitude of results from various comparator trials in a wide range of cancers; however, it was the presentation of clinical results from lesser known, and potentially just as exciting drug treatments, that turned heads.
RAD-001 was on everybody’s lips and results form a latebreaking Phase III trial even made it onto the front cover of the ASCO ’08 Daily News. In Saturday’s Genitourinary Cancer Oral Abstract session, researchers found it to be a safe and effective treatment for patients with metastatic renal cell carcinoma whose disease had progressed on VEGFr therapies. In the 410-patient trial, a median progression-free survival of 4 months was observed on RAD-001 compared to only 1.9 months on placebo. According to Dr. Motzer, of Sloan- Kettering Cancer Center, "This is the first Phase III trial that establishes clinical benefits and provides safety information for this new agent."
Targeted cancer therapies, such as Exelixis’ XL-765, a selective dual oral inhibitor of Class I PI3K isoforms and mTOR, were the topic of many clinical science symposia. XL-765 has shown potent in vivo inhibition of the PI3K pathway signaling leading to tumour growth inhibition or shrinkage in a dosedependent manner in multiple human xenograft tumor models exhibiting dysregulated PI3K pathway signaling. Activation of the PI3K pathway is a frequent event in human tumours, promoting cell proliferation, survival and resistance to chemotherapy and radiotherapy. mTOR is also often activated in human tumours and plays a central role in tumour cell proliferation. It can be activated via upregulation of PI3K, or via PI3Kindependent mechanisms. In the reported Phase I dose escalation trial, XL-675 administered to patients with advanced solid malignancies orally twice a day for cycles of 28 days up to 120 mg resulted in no dose-limiting toxicities. One nonsmall cell lung cancer patient had stable disease after 6 cycles and another patient with testicular carcinoma that had progressed under multiple chemotherapy regimes demonstrated a clinically-significant reduction in alfa-foetoprotein from 11,000 to 7,000 U/L and radiological stable disease after 1 cycle.
Sunday saw a plethora of talks and poster sessions take place, including a molecular therapeutic oral abstract session. Results from a dose-escalation Phase I trial of Curis’ hedgehog (Hh) pathway antagonist were among the abstracts presented. Aberrant Hh signaling pathway activation has been implicated in a variety of cancers via both Hh ligandindependent and -dependent overexpression. GDC-0449 is a first-in-human, first-in-class, potent systemic inhibitor of Hh signal transduction. It was shown that in 19 patients with refractory solid tumours non-respondent to prior therapy, GDC-0449 150-540mg/kg was safe and showed objective responses and clinical benefit. Two patients each with basal cell and adenocystic carcinoma had stable disease. There was 1 partial response in a basal cell carcinoma patient. It had a favorable pharmacokinetic profile with a t1/2\b of >7 days with no dose-limiting toxicities found.
In the same session, results from two Phase I trials for MK- 0646, a humanized IgG1 MAb that binds to IGF1R, were presented. IGF1R is a tyrosine kinase receptor that mediates both mitogenic and antiapoptotic pathways and has been found to be expressed in a variety of tumours. IGF1R activation also mediates resistance to a broad range of cytotoxic and targeted agents. In trial P001 in 53 patients with advanced solid tumours, MK-0646 1.25-20mg/kg iv every week was shown to be safe and tolerable with three patients having stable disease for over 3 months. It had a t1/2, Cl and AUC of 95hr, 0.007ml/min/mg and 39.4mg/ml/hr, respectively. The 2nd trial reported was P002 in 36 patients. It also showed that MK- 0646 was well tolerated at loading doses up to 20mg/kg and maintenance doses up to 15mg/kg.
Once again, ASCO’s annual meeting was a veritable success, fulfilling the foundation’s mission of providing and stimulating education and enthusiasm in the field of cancer research. We eagerly look forward to next year’s annual meeting certain that it will be even bigger and better than this year.
Sophie Green
Pharmaprojects Analyst
