Zosia Chustecka

May 25, 2012

May 25, 2012 — The theme of the 2012 Annual Meeting of the American Society of Clinical Oncology (ASCO) is collaborating to conquer cancer.

It was chosen by outgoing ASCO president Michael Link, MD, a pediatric oncologist at the Lucile Packard Children's Hospital at Stanford University in Palo Alto, California, and highlights the need for collaboration between cancer patients, physicians, and laboratory scientists.

"The progress that has been made against cancer in the last 40 years started with and continues to be led by progress made in children," said Nicholas Vogelzang, MD, chair of ASCO's Cancer Communications Committee. The field of pediatric oncology has seen particularly intense collaboration between these 3 players, and these close networks have pushed through major advances. "We now need to extend this to other cancer types," he explained.

Highly Anticipated Plenary Session

The meeting, being held once again at the McCormick Conference Center in Chicago, Illinois — where ASCO has booked a 10-year run for the meeting — is expected to attract more than 30,000 oncology professionals from around the world.

More than 4500 abstracts will be presented or published at the meeting. Many are already available online, but some of the most anticipated abstracts are still under embargo.

These include the abstracts from the plenary session on June 3, where the hottest news is in breast and prostate cancer.

Set to make a big splash is the very first plenary presentation, featuring the novel product trastuzumab emtansine (T-DMI, Genentech). The results from a phase 3 trial (known as EMILIA) in HER2-positive locally advanced or metastatic breast cancer will be presented (Abstract LBA1).

Although no details are available, Genentech announced in a press release in March that the trial was positive, and that it intends to file for approval of the novel product.

T-DMI is an antibody–drug conjugate in which trastuzumab acts as the homing device to deliver the cytotoxic agent DM1 into the HER2-positive cancer cell.

Results from an earlier phase 2 study were welcomed enthusiastically by breast cancer specialists, as previously reported by Medscape Medical News. Martine Piccart-Gebhart, MD, PhD, from the Jules Bordet Institute in Brussels, Belgium, suggested that this is the "magic bullet; the one we have all been waiting for." However, she emphasized the need for validation from a phase 3 trial. It is these results that will be presented.

Another big splash is expected from the plenary presentation on prostate cancer, which will address whether androgen-deprivation therapy should be administered continuously or intermittently. The results come from an international phase 3 trial (Abstract 4); the official program notes that this is a "this practice-changing abstract."

Amplifying Implications

In an interview with Medscape Medical News, Dr. Vogelzang said that some of the major news coming out of this year's meeting builds on recent breakthroughs.

An example is the "striking responses" seen in some pediatric tumors with crizotinib (Xalkori, Pfizer), recently reported by Medscape Medical News. This drug is approved for lung cancer, specifically for tumors harboring an ALK mutation, but it turns out that some pediatric tumors are "using the same genetic engine for their growth, so a pill for lung cancer may someday be a pill for leukemia as well" (Abstract 9500).

The implications from the original discovery "continue to be amplified," much like the concentric circles of waves that radiate from a splash in a pond, Dr. Vogelzang explained. "The implications become more obvious and more impactful," and then reach more patients. The original splash might be relevant to only a small number of patients (e.g., ALK mutations are found in only 5% of all patients with nonsmall-cell lung cancer [NSCLC]), but as the implications of the discovery are amplified, many more patients will benefit, he noted.

Another study that builds on a previous breakthrough screened more than 1000 patients with nonlymphoma malignancies for high CD30 expression (Abstract 3069). A drug targeting this molecular defect, brentuximab (Adcetris, Seattle Genetics), has recently been approved for Hodgkin's lymphoma, but the new study found the CD30 defect in patients with mesothelioma and in those with testicular and ovarian cancer. The next step will be to see if these patients respond to the drug, Dr. Vogelzang explained.

"These tumors are not intuitively linked," Dr. Vogelzang said. He emphasized the need for a new paradigm in which cancers are no longer considered by their location in the body, but by the genetic markers they contain.

"It's becoming more obvious each day that we can find better treatments for our cancer patients once we know their molecular characteristics...the Achilles' heel of the tumor," he added.

Long-Term Updates of Clinical Data

This amplification of implications will be seen in other plenary presentations, which feature updates on studies that have been ongoing for some time.

The German Study Group for Indolent Lymphoma (StiL) will present the latest results from a trial of patients with indolent and mantle cell lymphoma (Abstract 3). The trial compares 2 different approaches to first-line treatment, pitting the simpler 2-drug combination of bendamustine plus rituximab against the more complex standard treatment approach of rituximab plus the 4-drug regimen of CHOP (cyclophosphamide, hydroxydaunorubicin, vincristine [Oncovin], and prednisone).

Earlier results from this study, reported in 2009, suggested that the 2-drug combination was the better choice for first-line treatment, but there were no data then on overall survival; indolent lymphoma is a "long and slow disease," the researchers noted at the time.

Bendamustine is a decades-old drug, but it was given a new lease on life in 2008 when it was approved (as Treanda, Cephalon) by the US Food and Drug Administration (FDA) for first-line use in chronic lymphocytic leukemia (CLL). However, the dose used in indolent lymphoma is lower than that used for CLL.

The remaining plenary presentation features anaplastic oligodendroglioma, the rare primary central nervous system tumor. It will feature long-term follow-up results from a phase 3 trial (EORTC 26951) of adjuvant therapy with the 3-drug chemotherapy regimen of procarbazine, lomustine, and vincristine (Abstract 2).

Early results from this study, presented at the ASCO annual meeting in 2005, indicated that the addition of chemotherapy improves outcomes, compared with radiotherapy alone, but no overall survival data were available at that time.

New Drugs to Watch For

New cancer drugs that oncology market observers have highlighted as being of particular interest will make their debut at the meeting.

A new targeted immunotherapy (BMS-936558) is a fully human monoclonal antibody that targets PD-1 (programmed death-1), a coinhibitory receptor that negatively regulates T-cell activation. Several poster presentations will report on early phase 1 studies in kidney cancer (Abstracts TPS2614 and TPS2613) and NSCLC (Abstract TPS2615), and an oral presentation will report results in melanoma (Abstracts 8507 and 8582).

Afatinib (Boehringer Ingelheim), an ErbB family blocker, has activity against the epidermal growth-factor receptor (EGFR/ErbB1). Results will be presented from phase 3 trials in head and neck squamous cell carcinoma (Abstract TPS5598) in HER2-overexpressing metastatic breast cancer (Abstract TPS649), and in lung cancer (Abstracts 7557 and 7558). The big news will come from LUX-Lung 3, the pivotal trial in patients with NSCLC who are harboring an EGFR mutation (Abstract LBA7500). This is the largest phase 3 trial to date in EGFR-positive patients, and the first to use pemetrexed/cisplatin as a comparator in this patient population, according to a company press release.

Regorafenib (Bayer), an oral multikinase inhibitor, showed a survival benefit in metastatic colorectal cancer in the phase 3 trial known as CORRECT, which was reported earlier this year. Details will be presented at this meeting (Abstract 3502); these data have just been filed with the FDA for approval of this indication, Bayer announced recently. New data on this drug from a phase 3 trial in gastrointestinal stromal tumors (GIST) will also be presented (Abstract LBA10008).

Omacetaxine mepesuccinate (Teva Pharmaceutical Industries) is a first-in-class protein synthesis inhibitor for chronic myeloid leukemia. It is being investigated in patients who have previously been treated with 1 or more tyrosine inhibitor, including imatinib, dasatinib, and nilotinib (Abstracts 6513, 6596, 6604). Another novel product, blinatumomab (Amgen), has shown a high response rate in patients with relapsed or refractory acute lymphoblastic leukemia (Abstract 6550).

Late-Stage Cancer

Some rather surprising news coming out of the meeting concerns a lack of treatment for patients with late-stage cancer. A review of nearly 800,000 patients with late-stage cancer from the National Cancer Database from 2000 to 2008 found that 20% of these patients did not receive any anticancer treatment (Abstract 6065).

Unprecedented Activity in Prostate Cancer

Some of the news from the meeting was reported at a presscast held last week. Among the data highlighted there were those for abiraterone (Zytiga) in high-risk prostate cancer (Abstract 4521); results in clearing the tumor were unprecedented when the drug was used before surgery. Pharmaceutical analysis in response to this news indicated that this use could potentially double the market for the drug.

Data on 2 other novel agents that have shown unprecedented activity in prostate cancer with bone metastases will be presented. The resolution of bone scans after treatment with cabozantinib (under development by Exelixis) made headlines last year; further data on this activity will be presented this year (Abstracts 4513 and 4566). Cabozantinib, an inhibitor of MET and VEGFR2, has shown activity in several other cancer types, including breast, kidney, liver, and melanoma, and in a phase 3 trial in medullary thyroid carcinoma (Abstract 5508).

More data, including final overall survival results, will be presented for the novel radiopharmaceutical radium-223 chloride (Alpharadin, Bayer) (Abstracts LBA4512 and 4551), which has been proposed as a new standard of care for patients with castration-resistant prostate cancer with bone metastases.

A new approach to the treatment of prostate cancer is being tested with the first-in-the class agent enzalutamide (Medivation/Astellas), which acts as an androgen-receptor signaling inhibitor. Data from the AFFIRM trial will be presented (Abstract 4519).

Progress in Melanoma Continues

Progress in the melanoma field has dominated the news coming out of the annual meeting for the past 2 years, and there continues to be news in this field. The benefit of a combination of 2 experimental therapies — the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib (both under development by GlaxoSmithKline) — was highlighted at the presscast, but new results will show how each of these drugs performs alone (Abstract 8510).

Adverse Effects of Chemotherapy

Adverse effects from cancer treatment can sometimes stop patients from continuing with therapy, so new approaches to deal with adverse effects are always welcome. A study showing that the antipsychotic drug olanzapine reduces breakthrough nausea and vomiting induced by chemotherapy was discussed at the presscast (Abstract 9064).

Another complication in cancer patients, diarrhea associated with Clostridium difficile,has been shown to respond more quickly to the new antibiotic fidaxomicin (Dificid), approved in the United States a year ago, than to oral vancomycin. Symptom resolution was seen 2 days earlier (Abstract 9067).

Awareness of the long-term adverse effects of some commonly used chemotherapies is low among primary care physicians, according to a new survey (Abstract 6008). This is rather worrying, cancer experts noted at the presscast, because there are now 12 million cancer survivors in the United States, and once the cancer is in remission, the care of these patients passes from the oncologist back to the family doctor.


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