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McKesson-led Consortium to Establish Best Practices for Lung Cancer Molecular Testing, Treatment

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NEW YORK – After studying how some 12,000 lung cancer patients are receiving care across community practices, McKesson and its collaborators are hoping to establish best practices that can improve access to molecularly informed care.

McKesson, a provider of medical supplies, drugs, and health technology solutions, last month announced that a new consortium of oncology practices and drugmakers will conduct a three-part, five-year study to first identify the ways in which lung cancer patients in the community are currently receiving access to genomic testing, personalized treatments, and biomarker-informed drug trials, and then explore how to diminish the barriers they find. The goal of the MYLUNG (Molecularly Informed Lung Cancer Treatment in a Community Cancer Network) consortium is to translate the study findings into standardized testing and treatment algorithms across institutions and healthcare systems that bring precision cancer care to more patients. 

Non-small cell lung cancer is the current poster child for precision oncology. Due to the growing list of biomarker-guided therapy options, the National Comprehensive Cancer Network now recommends testing advanced and metastatic NSCLC patients for a broad panel of biomarkers to give them the best opportunity of receiving a drug based on a tumor alteration. The guidelines specifically recommend testing patients' tumors for alterations in EGFR, ALK, ROS1, BRAF, NTRK, and RET, and for PD-L1 expression. The NCCN also flags HER2 mutations and high MET amplification as emerging biomarkers. 

Amid increasing therapy options, genetic testing rates for certain tumor markers have increased because they are well known to the oncology community. For example, it has been a decade since Roche first released data from the EURTAC trial showing that erlotinib (Tarceva) nearly doubled progression-free survival in advanced NSCLC patients with certain EGFR-activating mutations compared to chemotherapy.

However, testing rates for genes that can guide treatment decisions for newly approved drugs, such as RET, are lagging, particularly in the community setting. In one survey released in 2016 by the nonprofit Friends of Cancer Research and the Deerfield Institute, 72 percent of 157 oncologists said they tested newly diagnosed NSCLC patients for EGFR mutations, but only 14 percent said they tested patients for RET rearrangements. Of the 36 community oncologists included in the survey, two thirds said they tested patients for EGFR mutations, while only three oncologists said they also offered testing for RET rearrangements. 

Drugs for RET-rearranged NSCLC — pralsetinib (Blueprint Medicines/Genentech's Gavreto) and selpercatinib (Eli Lilly's Retevmo) — came to market last year, which likely increased physician awareness of the need to test for this biomarker. Still, the testing trends identified in the 2016 survey still hold today, and the collaborators in MYLUNG see a lot of room for improvement. Currently, it can take up to a month from the time a lung cancer patient has a piece of tumor tissue resected at a cancer center to getting that sample to a lab for biomarker analysis and receiving the test report, estimated Robert Coleman, CSO at US Oncology Research, McKesson's network of investigators that specialize in Phase I-IV oncology trials.

In certain cases, doctors may get the molecular insights they need to make treatment decisions for patients in a few days if they order cell-free DNA testing, Coleman observed, adding that the MYLUNG consortium is trying to study what is and is not working within community practices and "come up with algorithms or patient flow opportunities that can be adapted as best practices at all kinds of differently resourced practices."

MYLUNG currently involves 10 community cancer practices; three drugmakers, Amgen, Eli Lilly, and Mirati Therapeutics; and three McKesson organizations, US Oncology Network, US Oncology Research, and the oncology data insights business Ontada. US Oncology Network includes 70 practices and nearly 1,400 oncologists who care for around 1.2 million patients in 25 states. US Oncology Research, meanwhile, comprises 60 sites that have conducted more than 1,600 clinical trials involving around 84,000 patients and played a role in the regulatory approval of more than 100 drugs.

In cancer care, an oft-cited statistic is that greater than 80 percent of newly diagnosed patients opt to be treated in the community setting. However, the practice closest to a patient's home may not have the resources to deliver timely, molecularly informed care, which often requires access to advanced diagnostics, genomics expertise, and clinical trials.

The consortium members will carry out three protocols within the study to get at some of the operational challenges hindering access. In the first protocol, researchers will draw on real-world data on 3,500 cancer patients within Ontada's iKnowMed electronic health records to identify standard practices when it comes to molecular testing in the community care setting. This will be a retrospective look within the US Oncology Network between 2018 and 2020 to assess what types of tests patients received, at what point in their cancer care tests were performed, and how the results informed their care.

In the second protocol, researchers will prospectively follow the experiences of 1,000 NSCLC patients treated at 10 community practices with expertise in lung cancer care. This part of the study began enrolling patients in the second week of January, and the goal is to observe the care patients are receiving. "We're not going to question them. We're not doing any special procedures," Coleman said. "We're just looking to see what is the normal flow [of care] in 2021 for newly diagnosed lung cancer patients and how molecular testing is operationalized."

Makenzi Evangelist, physician lead for the study and an oncologist at New York Oncology Hematology, one of the 10 practices included in the second protocol, noted that tissue acquisition is among the top barriers that she has been able to overcome. A few years ago, she was having difficulty acquiring enough tissue from her lung cancer patients for biomarker testing, but then the thoracic surgeons she works with agreed to perform biopsy procedures that get at the tissue needed but are safe for patients and have a quick recovery time.

"I've seen that change personally for me … but I work in a large practice with multiple offices across different hospital systems, and it's not that way for all my colleagues," Evangelist said. "They still struggle with that barrier."

Within MYLUNG, the aim is to identify these sorts of challenges, figure out what some practices are doing right, and then implement that at other practices, she said. One of the best practices she hopes will come out of the study is that cancer centers and hospitals should reflex-test for certain biomarkers for NSCLC patients. Evangelist and Coleman both acknowledged there is variability among community practices when it comes to multi-gene testing and that many practices are still assessing tumor biomarkers piecemeal, focusing mainly on the older, more well-known genes, such as EGFR, ALK, and ROS1, but not necessarily testing for the newer genes like BRAF, RET, and NTRK. This approach also quickly exhausts patients' available tissue.

But there may be lessons from how biomarker testing is handled for patients with other types of cancers. As soon as a sample is received by the pathology department from a breast cancer patient, they're going to be checking it for estrogen, progesterone, and HER2 receptor status, Evangelist pointed out, adding, "How do we make that routine for our patients with lung cancer?"

The findings from the first and second protocols of the study will help inform the interventional strategies that researchers will study prospectively in the third protocol. There, the goal is to enroll up to 7,500 NSCLC patients from another 20 practices over five years and delve into ways of optimizing aspects of patient care that are slowing down or hindering access to molecular testing and treatment. In this part of the study, researchers may explore in separate protocols, for example, how best to engage tissue navigators to ensure patients have sufficient tissue for biomarker testing, when to refer patients to genetic counselors, and how to speed up return of test results. Based on the findings, the MYLUNG consortium will develop best practices for dissemination and adoption by practices.

Within the study, consortium members will also be tracking how molecular test results informed patients' care — whether based on the biomarkers identified they received a US Food and Drug Administration-approved therapy, an off-label drug, or enrolled in a clinical trial. Within the US Oncology Network, practices have access to decision support tools that inform oncologists of standard-of-care treatments that a patient may qualify for based on their biomarkers but also clinical trials they might match to.

In step with increasing FDA-approved precision oncology therapies for NSCLC, there are also numerous drug trials exploring novel biomarker-defined hypotheses. For example, there are now multiple clinical trials enrolling lung cancer patients with KRAS mutations, a target that until recently was considered undruggable. "But if you didn't do the testing, you wouldn't know about the mutation … and the patient would potentially never have the opportunity to benefit from that," Coleman said.

The drug developers that have joined the MYLUNG consortium — Amgen, Lilly, and Mirati — may end up being competitors in the KRAS inhibitor space. Amgen is ahead of the pack and submitted a new drug application with the FDA in December for sotorasib as a treatment for previously treated, locally advanced, or metastatic NSCLC with KRAS G12C mutations.

Mirati's adagrasib (MRTX849), a KRAS G12C inhibitor, is in clinical development, and its MRTX1133, a KRAS G12D inhibitor, is in preclinical development. Lilly, meanwhile, had some bad luck with its KRAS G12C inhibitor last year and had to end its first-generation program due to "unexpected toxicity."

"These are potential competitors," Coleman said. "But I give them credit for coming together under a common mission to help us sort out how to do [molecular testing] in the most efficient way possible."

More efficient testing workflows can help drugmakers get their precision oncology drugs to the patients most likely to benefit from them, but they can also benefit other players in the space. Coleman said these firms certainly realized this but joined MYLUNG regardless. "They are looking at the greater good," he said. "And that's notable."