Immunotherapy investigation in melanoma is not a new trend in oncology as the indication received its first ever approval in early 2011 for Yervoy (BMS), anti-CTLA-4 monoclonal antibody, in unresectable or metastatic disease. Following this, a handful of immune checkpoint inhibitors have been approved till date as monotherapy or in combination with Yervoy such as Opdivo (nivolumab; BMS), Keytruda (pembrolizumab; Merck), Tecentriq (atezolizumab; Roche) and others. Key findings from this area are always much eagerly awaited at the various oncology medical conferences as it is the deadliest form of skin cancer and millions of people succumb to this disease globally each year. This time too, melanoma was under spotlight at ESMO 2021 annual meeting where biopharmaceutical like Merck, BMS, Alkermes, Targovax and others presented their crucial findings from their clinical trials.
As checkpoint inhibitors such as Yervoy, Opdivo, Keytruda have already been approved as the adjuvant therapy in melanoma after surgery to reduce the risk of stage III melanoma recurrence, there are only a few companies that talk about the stage II melanoma patients post-surgery. Taking this population into account, Merck presented the results from its pivotal Keynote-716 study, at ESMO 2021, which enrolled the patients with high-risk stage II melanoma (LBA3)
The first results from the study showed a statistically significant and clinically meaningful improvement in recurrence-free survival (RFS), the trial’s primary endpoint, compared to placebo in patients with resected high-risk stage II melanoma. At the first interim analysis, Keytruda reduced the risk of disease recurrence or death by 35% compared to placebo. Median RFS was not reached for either group and after a follow-up of 14.4 months, 11.1% of patients on Keytruda had recurrence or died compared with 16.8% of patients on placebo, with fewer distant recurrences with Keytruda. The safety profile of the drug was also consistent with previously reported studies in patients with solid tumors, with grade 3 or 4 TRAEs being observed in 16.1% versus 4.3% of patients, in the Keytruda versus the comparator arm, respectively.
Expert Opinion: “Patients diagnosed with stage IIB and IIC melanoma have a high risk of recurrence after complete resection and similar five-year survival outcomes as those with stage IIIA and IIIB disease, but because there are no systemic treatment options available, the standard of care is observation. The encouraging results from KEYNOTE-716 show that adjuvant treatment with pembrolizumab was associated with a significant reduction in disease recurrence or death versus placebo for patients with resected high-risk stage II melanoma and, if approved, may offer these patients a new treatment option.”
- Expert Opinion
INSIGHTS: As Keytruda, Opdivo and Yervoy are already approved as the adjuvant treatment for stage III disease post-surgery, Merck decided to investigate its blockbuster drug in stage IIb/IIc patients who have poorer prognostic factors just like stage III patients, and where the current treatment guidelines recommend simple observation for stage II melanoma. Based on its significant clinical benefit, the US FDA also accepted and granted priority review to a biologics license application (BLA) for Keytruda in the segment and assigned a Prescription Drug User Fee Act (PDUFA) goal date of December 4, 2021. It was also well stated by the company that KEYNOTE-716 is the first phase III study to evaluate adjuvant therapy solely for stage IIB and IIC melanoma—an area with a high unmet need. Besides melanoma, it has been observed that PD-1/L1 agents are increasingly chasing the perioperative cancer settings for their next phase of growth. The recent approvals of Keytruda in early stage triple-negative breast cancer and a go-ahead signal given by the US FDA for the adjuvant treatment of patients with renal cell carcinoma (RCC) following nephrectomy (Keynote-564) suggests that Merck still yearns to have Keytruda as the global product of the year before its patent expiration in various advanced and early staged cancers. Delveinsight is quite sure that the product, if approved, for stage IIb/IIc melanoma might generate a good market size globally and pose itself as a tough competition to BMS, as the asset inhibits recurrence in early stages.