Analyst Notes: Can new targeted treatments transform the treatment of colorectal cancer?

Checkpoint inhibitors continue their march into multiple areas of oncology, and are now approved as treatments for colorectal cancer (CRC). But while Keytruda (pembrolizumab; Merck & Co.) and Opdivo (nivolumab; Bristol-Myers Squibb) represent the most recent additions to the CRC treatment armamentarium, do key opinion leaders (KOLs) believe they'll make an impact? KOLs interviewed by FirstWord for a new report titled Colorectal Cancer: KOL Insight speak out on this issue, along with providing insights on new treatments in development and how the CRC treatment landscape could evolve in the future.

KOLs believe that the current stable of CRC treatment options are generally satisfactory, but traditional treatments, such as Avastin, Erbitux and other targeted therapies, are likely to be bumped down the treatment paradigm as treatment approaches become more personalised. As gene mapping increasingly becomes a part of the CRC diagnostic process, these therapies could be moved to lower lines in favour of more targeted therapies for better defined patient populations.

"I think that the most important change coming in the next five years is going to be personalisation of the treatment, so biomarkers that allow us to identify different treatments for different patients, not everything for everyone." - European Key Opinion Leader

As the newest market entrants, checkpoint inhibitors present an exciting treatment option for select cancer patients, but KOLs reflect that they're unlikely to significantly impact prescribing habits. A key driver of this belief is the limited labels granted to products like Keytruda and Opdivo, inasmuch they're only intended for use in patients with specific gene mutations, such as microsatellite instability high (MSI-H) metastatic CRC or patients with the mismatch repair (MMR) deficiency. Because these mutations are only observed in approximately 15 percent to 20 percent of CRC patients, the market impact of these drugs is likely to be muted until more data is provided.

"It's a relatively small subset of patients, because this MSI-H, at least the stage 2 patients, have a much better prognosis. It's a small subset of patients, at least in colon cancer." - US Key Opinion Leader

From a treatment guidelines perspective, data on left side versus right side tumours could usher in significant changes in the treatment algorithm for CRC, suggest KOLs. Data presented at the ASCO annual meeting suggests that patients with tumours that originate on the right side have lower rates of both treatment response and overall survival. Furthermore, patients with right-sided tumours have a better response to Avastin (anti-VEGF) compared to Erbitux (anti-EFGR), while the opposite was true for patients with left-sided tumours. Understanding where the tumour originates can thus be used to guide future treatment decisions.

"To be fair, it's not yet actually made a big difference, but it should. Particularly there are more data that have shown it's a prognostic effect, but they've demonstrated that there's a predictive effect of anti-EGFR therapies as well based on the right and left sidedness of the tumours." - European Key Opinion Leader

In the wake of the first Avastin biosimilar approval in the US, where Amgen received FDA clearancel for Mvasi (bevacizumab-awwb) in September 2017, KOLs seem to be warming toward bevacizumab biosimilars. With over a dozen additional Avastin biosimilars in development, KOLs are cautiously optimistic, but urge caution when using Avastin biosimilars when the CRC indication is awarded by indication extrapolation.

"I'm OK with extrapolation because Amgen has shown its product to have no clinically meaningful difference in terms of efficacy and safety in non-small-cell lung cancer. But I'd prefer efficacy of bevacizumab biosimilar be demonstrated in colorectal cancer than in lung cancer." - US Key Opinion Leader

KOLs are moderately excited about the therapies currently in development, but were unclear about which pipeline therapies could emerge as a market leader. KOLs also suggest that drugs currently under development would no longer be approved by simply being as good as currently available treatments, instead having to prove superior efficacy and/or safety.

For companies operating in the CRC market in Europe and the US, Colorectal Cancer: KOL Insight is a must read. The report provides actionable insights and commentary on some of the most critical issues in the CRC market, and provides perspectives on pipeline therapies and their potential in a rapidly increasing market. The report also discusses how treatment paradigms could change in CRC. For more information, please click here.

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