Foster Rosenblatt

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Foster|Rosenblatt Oncology Center of Excellence

PD-L1 Inhibitors – How many patients may eventually benefit from them?

Immunotherapy is the treatment of a disease with therapeutics that stimulate the immune response and this is not a new concept in cancer therapy. Recent attention has been focused on a class of therapeutics know as PD-L1 Inhibitors. Tumor cells have the ability to confuse the immune system by turning off the attack process of immune cells, specifically T-cells. PD-L1 inhibitors block a tumor cell’s ability to turn off the T-cell response allowing the immune system response to function as intended.

As of September 2016 there are 317 clinical trials ongoing related to PD-L1 inhibitors in various tumor types, with 61 of them in the Phase III setting. A decade down the road how will these studies play out and what might be the potential barriers to patient access for those regimens where evidence supports their use?

Using NSCLC as an example, based on the OncoEdge® oncology patient forecast model there are an estimated 55,000 PD-L1 positive patients in the US and another 68,000 in the EU5. Of these, there are 53,000 treatment candidates in the first line setting and 34,000 treatment candidates in the 2nd line setting.

Prior to the availability of the PD-L1 inhibitors Keytruda® (pembrolizumab, Merck) and Opdivo® (nivolumab, BMS) most NSCLC patients with EGFR or ALK receptor negative disease received first line platinum doublet chemotherapy which is available at a relatively low cost due to the multi-source availability of the drugs in the regimens. With the recent launches of Keytruda and Opdivo for the second line treatment of NSCLC the cost of therapy is increasing, and as these therapeutics potentially move into the first line setting it remains to be seen whether government and private payers will be able to accommodate the relatively high cost of therapy.

Combinations of immunotherapy checkpoint inhibitors (anti-PD-L1 and anti-CTLA4 therapeutics) and/or checkpoint inhibitors with chemotherapy will further increase the direct cost of drug therapy, and as such many countries around the world may struggle with how to pay for treatment costs. Increased focus on cost and value emerged as a major theme during the ASCO 2016 meeting and strategies are being implemented to address it.

Health system changes may be required to effectively optimize the use of PD-L1 therapies. PD-L1 inhibitors tend to be given over a longer duration than chemotherapy and as such the chair time requirements to administer them may eventually become a barrier to treatment in some countries. Assessment of the current and potential future infusion chair capacity would be a valuable exercise. Additionally, for those tumors that require the identification of high PD-L1 expressers, systemic changes may be required to accommodate testing and clearly identify the subset of patients that will benefit from treatment.

Finally, if the recent clinical trial results with Keytruda in NSCLC are a model for the requirement for testing PD-L1 status in order to support the use of an anti-PD-L1 therapeutic the cost of diagnosing the various types of cancer where PD-L1 inhibitors are effective will inevitably rise. Pharmaceutical and Biotech companies with PD-L1 inhibitors in their pipeline should ensure they are prepared to offer detailed recommendations to public and private insurers to support the overall cost and value of therapy.