ViewPoints: New data indicate key role for biomarkers in immuno-oncology development race

With the annual meeting of the American Society of Clinical Oncology (ASCO) sharpening focus on experimental immuno-oncology therapies, a key topic of debate in Chicago this past weekend was the role of biomarkers in shaping the development of these products and their commercial futures.

Insight, Analysis & Opinion

Roche – positioned at the vanguard of personalised medicine – continues to discuss the role of PD-L1 expression "as a predictive or prognostic biomarker," remarked Bernstein analyst Tim Anderson in a note to investors on Monday.

Studies presented by the Swiss company at ASCO support this stance. Roche's PD-L1 inhibitor MPDL3280A demonstrated robust data in bladder cancer, with particularly impressive results among those patients expressing higher PD-L1. Similarly, Merck & Co.'s MK-3475, also known as pembrolizumab, showed much greater efficacy in those head and neck cancer patients with higher expression of PD-L1.

The study for MK-3475 only enrolled PD-L1-positive patients, and Merck's drug demonstrated an overall response rate of 20 percent (an improvement over available care). However, in those patients with particularly high levels of PD-L1 expression, the response rate for MK-3475 was 45 percent, described as "incredible" by ISI analyst Mark Schoenebaum.
However, with patients whose tumours do not express PD-L1 also benefiting from treatment with these therapies in some cases, it remains difficult to draw conclusive findings.

Presenting at ASCO – Padmanee Sharma, associate professor in the Department of Genitourinary Medical Oncology at The University of Texas – also pointed out that as immune responses change over time, it is possible that tumours initially not expressing PD-L1 may do at a later date. She argues that instead of focusing on PD-L1 expression, it could prove more effective to measure T-cell infiltration into tumours as a prognostic marker.

A notable risk of utilising PD-L1 expression too 'stringently' is obviously depriving a patient access to a potentially effective therapy. As JP Morgan's Richard Vosser notes "many physicians at ASCO have highlighted that the PD-L1 negative responses are as good as approved agents."

Anderson suggests, however, that in price-conscious markets – which could effectively mean any territories outside of the US – payers may potentially enforce the use of PD-L1 biomarkers "more aggressively," particularly as immuno-oncology therapies may set new benchmarks in terms of pricing.

A number of analysts have raised the issue in recent months that PD-L1 expression (or lack off) could reshape commercial expectations as market opportunities are resized, such as in the non-small-cell lung cancer segment; Schoenebaum cites Bristol-Myers Squibb's ASCO abstract for nivolumab monotherapy in PD-L1-negative patients, which demonstrated a 0 percent response rate.

Roche has suggested that although PD-L1-negative patients should not necessarily be excluded from treatment with a therapy based on biomarker status alone, physicians are likely to benefit from knowing whether a patient over expresses or not as this could play a pivotal role in shaping the aggressiveness of the treatment regimen. Similarly, combination therapies could benefit those patients who are PD-L1 negative, adds the company.

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