The conference, chaired by Thomas J. Lynch, MD, director of the Yale Cancer Center and physician-in-chief at the Smilow Cancer Hospital in New Haven, Connecticut, consisted of three panel discussions with a “medical crossfire” format: (1) the role of antibodies and maintenance therapy for patients with advanced disease; (2) the role of EGFR- and ALK-targeted therapies in non-small cell lung cancer (NSCLC); and (3) the implications of ongoing clinical trials investigating the role of immune-based therapies in lung cancer.
Lynch is among the inaugural class of oncology specialists honored as one of the “Giants of Cancer Care,” a new awards program that the Intellisphere® Oncology Specialty Group launched last year. He has conducted dozens of studies focused on personalized cancer therapies, including codirecting one of the research teams that delineated the role of EGFR mutations in treatment response to the targeted therapy gefitinib among patients with NSCLC (N Engl J Med. 2004;350:2129-2139).
“A fundamental shift in the treatment of lung cancer has occurred in the past five to 10 years, from a one-size-fits-all approach to the emergence of therapy that is personalized based on the histologic and molecular characteristics of the tumor,” said Lynch, setting the stage for the program’s panel discussion focused on treatment of patients with NSCLC whose tumors harbor EGFR mutations or ALK translocations.
“While the advances in new targeted therapies offer the possibility of improved outcomes to patients, they complicate the decision-making process that community oncologists face each time they consider treatment options for their patients,” said Lynch. These decisions involve such questions as which patients should be tested, when they should be tested, which test to order, the costs of these tests, and how to handle a patient with more than one mutation.
EGFR—10 Years LaterThe panel discussion that focused on personalized therapy, noted faculty member Balazs Halmos, MD, proved “especially momentous,” occurring about the time of the 10th anniversary of the discovery of the EGFR mutation’s impact on treatment outcomes for patients with that aberration.
As part of his presentation, Halmos, section chief of Thoracic Oncology at New York-Presbyterian Hospital/Columbia University Medical Center in New York City, described studies demonstrating the benefits of the tyrosine kinase inhibitors (TKIs) gefitinib, erlotinib, and afatinib in the frontline setting for patients with EGFRmutated NSCLC, as powerful examples of how molecular profiling has transformed treatment options in lung cancer.
One of the big questions physicians face when presented with a patient who is newly diagnosed with metastatic lung cancer, said Halmos, is whether to wait to get the results of molecular testing. Ideally, the turnaround time for such testing should be 2 weeks or less, he continued, but this must be balanced against the need to treat highly symptomatic patients. He noted that practitioners may be reassured by research findings showing that patients initially treated with chemotherapy can successfully be transferred to TKI therapy should testing results warrant.
Halmos also mentioned a resource he finds very useful in keeping up with research developments in the complex arena of genomic profiling: the My Cancer Genome website (www.mycancergenome .org), which is managed and updated regularly with new research results by the Vanderbilt-Ingram Cancer Center based in Nashville, Tennessee.
Therapies for ALK-Positive PatientsALK gene rearrangements present another personalized therapy target, and crizotinib has been found to be a beneficial treatment for patients with ALK-positive NSCLC. When crizotinib resistance occurs—and depending on the type of progression—patients will require either additional localized therapy or a switch to something different, such as one of the promising second-generation ALK-inhibitors, for example, ceritinib (LDK378) or alectinib, said Gregory J. Riely, MD, PhD, a medical oncologist at Memorial Sloan Kettering Cancer Center in New York City. In identifying his most important takeaway point, however, Riely stressed the importance of therapeutic restraint in this setting: “Managing acquired resistance sometimes means holding back on changing treatments,” he said.
What are some of the clinical cues for the practicing doctor for determining when ALK testing is warranted? Sarah B. Goldberg, MD, MPH, an assistant professor at the Yale School of Medicine, explained that these indications are similar in some ways to those found in patients whose tumors have EGFR mutations—patients tend to be younger, never-smokers or light former smokers, with histologic observation of signet ring cells. “All that being said, I still test all of my patients,” Goldberg continued, “because the phenotypes are not that clear-cut,” and these tip-offs do not confer a definitive correlation.
For patients with ALK-positive tumors who are receiving crizotinib therapy, some of the more common adverse events that clinicians should be aware of include minor “light-dark” vision changes, fatigue, and gastrointestinal toxicity, said Goldberg. Overall, however, she said that she finds the drug to be very well tolerated, and when warranted, a dose reduction often helps, though it is not typically necessary.
Opportunities AheadLooking ahead, the panel members cited the need to go beyond EGFR- and ALK-targeted therapies and identify other tumor drivers as a research priority, along with directing patients to the appropriate clinical studies to tap the growing potential in this area.
Pointing to remarkable remissions that are being achieved with therapies available right now in the clinic, Halmos urged researchers and practitioners to “aim very high.”
“This is a time when we should be very optimistic about what lung cancer care should be in the coming years,” said Halmos, adding that based on his own calculations, in the United States alone, some 50,000 patients have been able to celebrate an additional anniversary in the 10 years since Lynch and colleagues elucidated the EGFR mutation.