This week Merck & Co.’s Keytruda pipped Bristol-Myers Squibb’s (BMS) Opdivo to the post for approval in SCCHN, after what proved to be a fiercely fought drug development race in the indication.1
The priority review designation for Keytruda in SCCHN was based on updated data from the phase Ib KEYNOTE-012 trial that was first presented at the European Cancer Congress in September 2015.2 To date, only a handful of companies have filed for approval based on Phase I data in SCCHN, and this confident move by Merck & Co. has paid off, securing the company first to market status in this indication. Meanwhile, BMS opted for a more conservative approach with Opdivo in SCCHN, waiting for data from the Phase III Checkmate-141 study before filing with the FDA and EMA in July 2016.3
Both Keytruda and Opdivo have shown great promise in clinical trials for previously treated recurrent or metastatic SCCHN (see “Data for Keytruda and Opdivo in SCCHN”), and are now also being trialed in numerous Phase III trials in the first-line setting in an array of combinations. Whether physicians will be comfortable prescribing Keytruda based on Phase I data is yet to be seen, however, historical evidence from malignant melanoma suggests that physicians will not regard the availability of only early-Phase data as a barrier to prescribing.4 Assuming future approval for Opdivo in SCCHN, the influence of physician experience and familiarity with both agents will have an interesting impact on their prescribing decisions. While Keytruda holds the first to market advantage, Opdivo has garnered wider uptake across multiple indications (see “Initial Approvals for Opdivo and Keytruda by Indication”) and may benefit from broader physician familiarity.
While experts are enthusiastic about the role of immunotherapies in SCCHN many feel that optimization of the agents will be necessary in order to enrich the patient population likely to respond, as well as to establish when and how best to combine these therapies with other treatment modalities, including surgery and radiotherapy. Most of the Phase III SCCHN trials of immune checkpoint inhibitors are currently evaluating the agents in the advanced recurrent or metastatic SCCHN settings and have been designed with planned subset analyses by PD-L1 expression, however in SCCHN like other tumor types, PD-L1 status has shown limited potential as a robust biomarker for response to these agents. Furthermore, SCCHN differs distinctly from other oncology indications with regards to symptom burden and quality of life issues due to the regional anatomy of the tumors, with treatment often impacting the basic functions of sight, speech, swallowing, hearing, and sense of smell. Developing better predictive biomarkers and optimum combinations with other immunomodulatory agents and treatment modalities could potentially add therapeutic benefit while maximizing SCCHN patient’s quality of life.
The approval of Keytruda for SCCHN is likely to be just the tip of the iceberg for the indication, with Opdivo’s approval expected by the end of 2016 and a promising pipeline of immune checkpoint inhibitors in development. The strengthened pipeline and interest from drug developers is likely to lead to increased market competition in SCCHN, and the high unmet need in this disease accompanied by an increased number of treatment options is likely to fuel future market growth.
Further insights and analysis of the clinical development of immunotherapies in SCCHN will be available in our 2016: SCCHN Disease, Landscape and Forecast content, which will publish in December 2016.
- Merck & Co., press release, August 8, 2016.
- Merck & Co., press release, April 13, 2016.
- BMS, press release, July 18, 2016.
- Decision Resources Group. Malignant Melanoma Disease Landscape and Forecast (2015).
- Merck & Co, press release, June 6, 2016.
- Ferris R, Further evaluations of Nivolumab versus investigator’s choice chemotherapy for recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN): CheckMate-141. American Society of Clinical Oncology Annual Conference. June 2016. Abstract No. 6009.