Precision Medicine and Immunotherapy Highlighted at ASCO 2018

August 2018 Vol 11, Special Issue - Conference Highlights ASCO
Wayne Kuznar

Chicago, IL—Interest in personalizing medicine in oncology is growing, so the American Society of Clinical Oncology (ASCO) titled its theme for the 2018 presidential address at the annual meeting, "Delivering Discoveries: Expanding the Reach of Precision Medicine."

Overall, 2515 abstracts were selected for presentation at the meeting. More than 39,000 attendees heard sessions highlighting the emerging role of precision medicine—in research as well as in the day-to-day care of patients.

ASCO President Bruce E. Johnson, MD, FASCO, Chief Clinical Research Officer, Dana-Farber Cancer Institute, Boston, delivered the presidential address on innovation in personalized medicine, highlighting how new discoveries in precision medicine, including immunotherapies, are transforming cancer care.

The theme of immunotherapy is directly connected with personalized medicine, as new targeted therapies and different types of immunotherapies are advancing the personalization of cancer treatment, with the most recent advance of immunotherapy—chimeric antigen receptor (CAR) T-cell therapy—named by ASCO as "the 2018 advance of the year."

Dr Johnson highlighted one area that especially demonstrates the revolution in cancer therapy and best demonstrates the success of precision medicine in lung cancer, namely, targeted therapy or immunotherapy, which has focused on personalizing the treatment of patients.

"Today, nearly half of all patients presenting with lung cancer can now be initially treated with targeted agents or immunotherapy rather than chemotherapy—half of all patients with advanced lung cancer, about 70,000 a year," Dr Johnson said, noting that knowing the precise type of lung cancer ensures better results based on the patient's unique and genomic characteristics, especially in non–small-cell lung cancer (NSCLC).

The success of precision medicine in lung cancer has resulted in the identification of more oncogenes, or biomarkers, which led to the development of many effective targeted therapies, as well as the "coming of age" of immunotherapy, "which is playing a pivotal role in the treatment of many patients with lung cancer," said Dr Johnson.

Dr Johnson reminded attendees that at the ASCO 2000 meeting, investigators from a cooperative group delivered data from a study comparing 4 chemotherapy regimens for NSCLC, and the published manuscript 2 years later had no mention of the cancer histology or how many patients were smokers.

"Contrast it to today: whether a patient smokes is now one of the most important pieces of information in their patient history. This is because patients who don't smoke are more likely to have genomic changes that can be targeted by existing treatments, and patients who do smoke are more likely to respond to immunotherapy."

In all, 4 EGFR tyrosine kinase inhibitors (TKIs) are now approved by the US Food and Drug Administration (FDA) and around the world for patients with lung cancer associated with EGFR mutations. EGFR TKIs are part of the initial treatment for approximately 15% of patients with NSCLC in the United States, and their outcomes are much better than patients who receive chemotherapy.

"Patients with these EGFR mutations are likely to live for 2.5 years from their diagnosis of metastatic lung cancer, while those without the mutation treated with chemotherapy survive for less than half the time, about a year," Dr Johnson said.

"The testing for mutations in the EGFR receptor in patients with advanced nonsquamous NSCLC now takes place around the world and is a part of routine care for more than 85,000 patients in the United States," he said.

The next oncogenic driver in lung cancer to be successfully targeted was ALK rearrangement, initially with crizotinib (Xalkori) as the main treatment, but now with newer agents recently also approved by the FDA for this specific subtype. A 2013 clinical trial comparing the outcomes of patients with ALK-positive NSCLC who received crizotinib or single-agent chemotherapy showed a 2-fold prolonged progression-free survival among the patients who received crizotinib versus chemotherapy.

"Among those patients with ALK-positive NSCLC who respond to the targeted agent crizotinib, and now other ALK-directed agents, there are patients whose responses now go on for years and have a dramatic impact on their lives," Dr Johnson said.
Discoveries in immunotherapy have been turned into significant treatment advances for patients with cancer. The class of drug directed against PD-1/PD-L1, also known as checkpoint inhibitors, are now being used worldwide as anticancer agents, with significant improvements in survival and patient quality of life.

Although the pioneering work with checkpoint inhibitors took place in melanoma, these agents have proved active in patients with lung cancer and other types of cancer, such as bladder cancer.

In 2018, almost 50% of patients with NSCLC can be treated with targeted therapy or immunotherapy as the initial agent.
More recently, CAR T-cell therapies, also known as gene therapies, have been successful in inducing durable responses in patients with hematologic ma­lignancies, including leukemias and lymphomas, and now the technology has been shown to do the same in multiple myeloma.

At ASCO 2018, recent results with CAR T-cell therapies for the treatment of patients with multiple myeloma and for relapsed or refractory non-Hodgkin lymphoma were featured, with an overall response rate of 81% obtained in multiple myeloma.

Other topics discussed in this issue include examples of precision medicine in targeted therapies, immunotherapies, and genomic markers, including the emergence of pembrolizumab (Keytruda) as standard up-front therapy for NSCLC; data on the use of the immunotherapy combination of niraparib (Zejula) plus pembrolizumab for the treatment of NSCLC ; promising phase 1 results from a study of a RET inhibitor for the treatment of cancers with RET alterations; and an immunotherapy combination for the treatment of triple-negative breast cancer and ovarian cancer.

An article on the IMPACT clinical trial provides further evidence that targeted therapy works, demonstrating that selecting a targeted therapy based on patients' tumor molecular analysis independently predicted longer overall survival compared with nonmatched therapy across a diverse set of tumor types.

Dr Johnson concluded with a call to action to attendees: "Given my personal encounter with prostate cancer, I now have personal insights into the anxiety faced by many of our patients about the return of their cancer. I want to remind you, as we do our work and see our patients, we must be mindful of the roles we can play beyond selecting the appropriate therapy for our patients and see to the psychological needs of our patients as well."

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