Dr. Edward S. Kim
Q: What research presented at the Annual Meeting provided key data about drug activity across tumor types?
Dr. Kim: This year’s Meeting was incredible in terms of the amount of precision medicine and molecular data presented. It’s tough to digest all of that for a practicing physician. It renews a lot of optimism among oncologists and oncology health care professionals that we are making a significant step in a positive direction for patients, and that there are options available—perhaps not yet the standard of care, but certainly on clinical trials where you see benefit.
The headline is always immunotherapy. In lung cancer specifically, we are seeing biomarkers help define the population, and we are seeing the incredible activity of immunotherapy combined with chemotherapy for defining new treatment standards. We may be witnessing some new level-setting regarding what standard therapy looks like and how well it works.
Keynote-407 and Keynote-189 have defined new standards of care in lung cancer treatment (in combination with chemotherapy) regardless of PD-L1 marker status.1,2 IMpower131 showed some intriguing data on first-line treatment of advanced squamous non–small cell lung cancer (NSCLC) with atezolizumab plus chemotherapy.3 The benefit was across all PD-L1–expressing subgroups and was enriched in those with high PD-L1 expression. Keynote-042 was a very important trial that showed that when you enrich for PD-L1, you can achieve benefit with a single agent as opposed to cytotoxic chemotherapy.4 In this case, pembrolizumab was given as first-line therapy for patients with advanced/metastatic NSCLC who expressed PD-L1 ( ≥ 1% level). The trial is an indication of what we hope for with precision medicine: the ability to give less therapy without sacrificing clinical benefit.
Another trial looked at using entrectinib, a TRK, ROS1, and ALK inhibitor. The study found that entrectinib was active in several fusion-driven solid tumors. There was robust activity of tumors harboring NTRK, ROS1, or ALK gene fusions, regardless of the tumor type and in pediatric as well as adult tumors.5
The LOXO-292 data show promise for using the RET inhibitor for treating patients with cancer that have RET fusions, which includes NSCLC, papillary and other thyroid cancers, and a few other malignancies.6,7 It’s another example of a rare mutation, yet a drug that shows very good activity. Another abstract found that microsatellite instability-high (MSI-H) tumors are more likely to have Lynch syndrome.8
Q: What are the implications of these biomarker data for standard use of broader genomic testing?
Dr. Kim: At some point it will beg the question of whether we should be incorporating NTRK fusion or RET fusion into testing prior to initial treatment. It’s tough to do unless you are using a large genomic platform up front, and it’s a difficult decision for many institutions. The question is, if we keep adding one additional marker or two additional markers to a panel, is it going to be tough to continue to run these smaller panels? If you run a large panel, about 95% of the information is not going to be used clinically at this time, although it’s attractive for research because you get additional information.
But as more of these drugs targeting specific biomarkers are approved, we will have to decide how many more markers we need to measure to faithfully make treatment decisions. The NCI-MATCH (Molecular Analysis for Therapy Choice) and ASCO’s TAPUR (Targeted Agent and Profiling Utilization) trials will provide us information about the success of doing these broad genomic screenings.
Q: How can this information about tumor types and targeted drug therapy be applied in clinical practice?
Dr. Kim: We want to be careful about moving ahead and applying treatments before they are U.S. Food and Drug Administration (FDA)-indicated, because we don’t want to put ourselves, or our patients, in a reimbursement bind. Technically, if a treatment does not have an FDA indication, there’s a risk that it’s not reimbursable, and then someone is left holding a very large bill. I do think, however, that in the very near future we are going to have a new standard in patients with squamous NSCLC.
We feel that there are many more options out there to effectively treat patients with advanced cancer. Because of that, there is a benefit to exploring clinical trials like ASCO’s TAPUR study and the NCI-MATCH or any other of these larger, umbrella-type studies that have molecular therapies associated with them. We are seeing more biomarkers appear, and we are seeing benefit with existing drugs that can be matched to biomarkers. The importance of these studies is also to prevent practitioners from continuing to do something that they shouldn’t. A lot of these genomic markers are being run, prompting some physicians who see a marker on a report to think that he or she can get this drug that’s approved in a different indication and give it to patients in the hopes it might work.
But as much as there is a promise of targeted therapy or precision medicine, we also must know when it is not the right time to use it with certain markers and with certain drugs. We still have immunotherapy trials that fail in certain areas, and we see targeted therapy fail in certain situations. That’s an important message and should make us stop overtreating the patient and stop putting resources into efforts that obviously don’t work.
Q: What did you hear from attendees at the Annual Meeting about this issue?
Dr. Kim: I heard that there was certainly an avalanche of molecular data presented—and again, much of it was positive and optimistic. I also heard concern in regard to organizing individual health care systems, clinics, processes, and methodologies in order to conduct or implement precision medicine. That is a struggle for some places. They see a new marker and get optimistic, but then have questions, such as, ‘Am I going to have to order a big panel on everyone?’ and ‘How can I get this for my patients?’
Operational feasibility can be just as stressful as trying to understand all the genomic data. Patients are going to come in asking about it because it’s on the news and it’s exciting. You can have all the greatest therapies and biomarkers, but if your infrastructure in general is not built for the practice of precision medicine, then it’s going to be a struggle.
Many health care professionals will return to their practices after the ASCO Annual Meeting and ask their pathologists and their laboratory people regarding genomic medicine: ‘Can we do this?’ ‘How can we do this?’ and ‘What do we need to do this?’ That’s equally challenging. It happens in the academic setting as well because many academic centers don’t have the equipment or their processes are dated. The ultimate challenge is not only keeping up with the rapidly changing data, but also the operational feasibility of implementing precision medicine into the respective communities.
–Kathy Holliman, MEd