The European Multidisciplinary Cancer Congress (EMCC), took place September 23–27 in Stockholm, brought together the European oncology community in a joint effort between the European Society for Medical Oncology (ESMO), the European Cancer Organisation (ECCO), and the European Society for Therapeutic Radiology and Oncology (ESTRO).
The multidisciplinary nature of the meeting is highlighted by the tagline of the congress—“Integrating basic and translational science, surgery, radiotherapy, medical oncology and care”—and, indeed, the meeting has emphasized the integration of these components and their important roles in driving cancer research toward providing better patient treatment and care. As clinical practice is becoming increasingly interdisciplinary with patients being treated in multidisciplinary teams, a multifaceted meeting such as this one is important for the continued dialogue, education, and communication among cancer clinicians and researchers.
The EMCC had 285 sessions and over 2,000 presentations from 707 experts in the field, with over 16,000 attendees from around the world.
A call to drive better personalized care deliverables for patients
The opening session of the EMCC emphasized that the field of oncology should continue to strive torward streamlined and personalized patient care. José Baselga, MD, PhD, the associate director and chair in hematology/oncology at the Massachusetts General Hospital Cancer Center gave a presentation, “New World of Cancer: Personalized Medicine for All Patients” that urged the cancer community to see molecular targeting of cancer as a new era. Dr. Baselga pointed out that he believes that classic approaches to cancer therapy such as radiation therapy and chemotherapy have achieved a plateau in terms of patient response. In this “classic therapy” era, only an empirical approach to clinical trial design was possible, where patient populations were unselected and large-scale trials were necessary in order to see any treatment benefit. These types of trials led to a high failure rate and minimal benefits. “The system can no longer tolerate an incremental benefit,” he stated as he transitioned to a discussion of what he calls the “new era of molecular targeting of cancer.”
As researchers and clinicians are beginning to understand the wiring of cancer and the underlying molecular causes, Baselga stated, “we are getting into an era of the right drug for the right tumor.” He went on to highlight that identifying the right molecular targets can result in the creation of specific molecules that act on these targets, and said, “chemistry is on our side, to design new treatments.” Dr. Baselga cited early success stories of targeted therapies that have resulted in dramatic patient benefits, including gefitinib (Iressa) and erlotinib (Tarceva), two selective inhibitors of EGFR for lung cancer, crizotinib (Xalkori) for lung cancer patients, which inhibits ALK in patients that harbor the EML4-ALK fusion; and vemurafenib (Zelboraf), the BRAF inhibitor that has recently been approved for metastatic melanoma.
“We will have an incremental number of genetic mutations identified in tumors and we will have an increased number of therapies to treat these tumors,” Baselga said, highlighting his optimism in the collaboration of bench-scientists and clinicians to develop new treatments, in conjunction with the increasing understanding of cancer mutations from patient tumor data.
“We have to realize that this is a watershed moment in cancer history. We have to make sure we match each drug with each individual tumor and we have to change the way we test these new drugs,” said Dr. Baselga.
Looking forward, Dr. Baselga spoke about the need for better, streamlined, and throughput methods to test these new agents for efficacy in a rational way that will provide meaningful data. After isolating compounds that have the potential to be efficacious, the ability to identify patients that will benefit is crucial. Baselga stated, “We have to embark on a comprehensive genetic characterization of tumors: chrosomomsal alterations, epigenetics, mutations, and proteomics.”
While the challenging tasks of platform and clinical validation, archiving quality specimens, improving turnaround time and informatics approaches, and looking for novel mutations is daunting, it is “far less than treating patients with expensive drugs that may not work unless they are targeted for the patient.” In this sense, the field has progressed significantly over the last decade, with the mutational landscapes for lung and breast cancers providing a categorization of subclassifications of these disease that facilitate tailored therapy treatments.
Baselga pointed out that one highly important point that, thus far, has not been widespread due to high cost and the inability to obtain appropriate patient sampling, is the serial monitoring of tumors during therapy. Looking at the genetic makeup of a tumor prior to and post-treatment will greatly facilitate the knowledge about how tumor genetic factors influence treatment response and resistance. Baselga cited the new research on circulating tumor cells (CTCs), and said that by applying novel therapies earlier in disease “you can identify very early on when a patient responds, which can help clinicians modulate therapy.”
He highlighted a particular example of the use of technology to predict response that was subsequently presented at EMCC (Gamez et al. “FDG-PET/CT for Early Prediction of Response to Neoadjuvant Lapatinib, Trastuzumab, and Their Combination in HER2-positive Breast Cancer Patients: the Neo-ALTTO Study Results, abstract #5013).
Dr. Baselga ended by listing his vision of novel clinical trial design in the new molecular era: 1) smaller smarter clinical trials without the need for 1000+ , expensive trials, 2) the importance of combination treatments 3) applying novel targeted agents earlier in the course of disease, and 4) the study of resistance to therapies. “Over the course of the next ten years,” he said, “we need good biomarker programs and facilities, the sharing of data, attracting the best pool of physician scientists into our culture of teamwork, and we need creativity and willingness in our clinical trial design.”
A pragmatic assessment of today’s personalized molecular medicine
Following Dr. Baselga’s talk, Gordon B. Mills, MD, PhD and chairman of the department of systems biology at the M.D. Anderson Cancer Center addressed what the cancer community needs to be doing to deliver personalized medicine outside of the research environment. “We have to determine to work with medicine and industry in a better manner. Drugs coming out of the pipeline must be linked to the right patient,” he stated.
Professor Mills defined personalized medicine as “the right treatment for the right person at the right and first time,” in contrast to the current practice of “trial and error.” He asked the audience to think about whether they are educating patients and physicians enough and whether they are overpromising on what the current treatments and care can deliver.
In the view of Professor Mills, there are still only subpopulations of patients that experience the biomarker benefit, calling the current phase “stratified and precision medicine.” He stated that he agreed with Dr. Baselga that breast cancer is leading the way in this. “Breast cancer is now a series of different diseases, at least eight of them. But the problem is that some of these subpopulations are too small to have clinical trials that will show good enough data. Rather than distinct diseases, currently, there are still only subpopulations,” he asserted.
Emphasizing that despite the latest positive results with targeted agents, “every single patient on [vemurafenib] has recurred.” His goal was for the oncology community to aim for higher achievements.
Finally, Professor Mills outlined the current landscape of challenges he sees that need to be overcome. In terms of patients, these include the need to identify a patient’s genetic makeup to determine whether a treatment will succeed, the need to assess individualized dosing and toxicity limits, and the issue of intra-tumoral heterogeneity and the evolution of the tumor from primary to recurrent stages of cancer.
As far as technology challenges, filtering passenger vs driver mutations is necessary, and Mills also cited the need to find actionable aberrations, as there are still a limited number of drugs for all of the mutations identified in tumors. He highlighted the fact that most tumor suppressors are still recalcitrant to treatments and that the cost of treatments is continually on the rise.
The issue of the accrual of large amounts of sequencing information is such that database storage costs outweigh the costs of generating sequencing data, and said that this is something that needs to be addressed. “The $1000 genome is now the $100,000 analysis cost,” he said. Lastly, he pointed to the expanded number of parties that are involved in treatment development and implementation. He stated that the ethics of telling patients about germ-line mutations that are discovered during genomic sequencing needs to be discussed thoroughly, and mentioned the need for participation by the U.S. Food and Drug Administration in the education of patients and physicians and the issue of reimbursement for testing and sequencing.
The communication, education, and open dialogue about these issues going forward among the global oncology community and other key stakeholders, as well as about novel treatment paradigms and progress, will be highly important for oncologists to be fully entrenched in this promising molecular therapy era.