Merck details Keytruda’s post-surgery lung cancer win

USA – Merck has released specific data for Keytruda in early-stage lung cancer, indicating an advantage over Roche’s first-to-market Tecentriq.

Postsurgery use of Keytruda reduced the risk of disease recurrence or death by 24% over placebo in patients with stage IB to IIIA non-small cell lung cancer regardless of tumor PD-L1 expression status.

Merck presented the findings of the phase 3 Keynote-091 trial, also known as PEARLS, at a plenary session of the European Society for Medical Oncology (ESMO).

Since Merck announced the headline win in January, industry observers have been betting on what appears to be an advantage over Roche’s Tecentriq, which became the first immuno-oncology agent approved in the adjuvant NSCLC setting last October.

Tecentriq’s approval, on the other hand, was limited to stage II to IIIA disease with PD-L1 expression covering at least 1% of tumor cells.

“The take-home message is that [Keytruda] looks to be an important addition for pretty much all comers with non-small cell lung cancer who are undergoing surgical resection,” Roy Baynes, M.D., Ph.D., chief medical officer of Merck Research Laboratories, said in an interview.

Given the limitations of Tecentriq, the key question is how Keytruda performed in patient subgroups, particularly those with stage IB or PD-L1-negative disease.

Previously, in the IMpower010 study, Tecentriq improved disease-free survival by 19% in adjuvant NSCLC or 34% when stage IB and PD-L1-negative patients were excluded.

Keytruda’s performance

According to the presentation at the ESMO Plenary, Keytruda reduced the risk of disease recurrence or death in patients with stage IB disease by 24% compared to placebo. And in PD-L1-negative patients, the figure was 22%.

Keytruda’s performance in patient subgroups was described by Baynes as “broadly convergent,” though he cautioned against reading too much into the analyses given the small patient numbers in each group.

However, in a previously announced dataset, Keytruda only showed an 18% disease-free survival benefit in patients with PD-L1 expression of 50% or higher. As a result, the trial has not yet met one of its dual primary endpoints.

The data from Keytruda contradicts that of Tecentriq. In Tecentriq’s study, among stage II to IIIA patients, the Roche PD-L1 inhibitor only provided a 13% disease-free survival advantage in those with PD-L1 expression ranging from 1% to 49%.

What this data implies is that it was the PD-L1-high patients who drove the 34% benefit in PD-L1 all comers.

Baynes attributed the failure to a low rate of disease recurrence or death in the PD-L1-high group. At the time of the data cutoff, 117 events had occurred in 333 PD-L1-positive patients.

Merck believes that with a longer follow-up period, the PD-L1-high data will become significant. What’s more, Keytruda also showed a favorable trend that it could extend patients’ lives at the interim analysis by paring down the risk of death by 13%.

NSCLC market size

Postoperative NSCLC is a sizable market. According to Baynes, approximately one in every two NSCLC diagnoses has operable tumors, and despite surgery, approximately one in every two patients will recur.

There has also been discussion about whether immuno-oncology agents should be used prior to or after surgery.

Keytruda stops cancer cells from shutting down the body’s defense system. Cancer cells have a protein that binds to a receptor on T cells, which tricks them into not going on the attack.

The Keytruda monoclonal antibody binds to this receptor instead, foiling the cancer’s trick and allowing the immune system to fight the disease.

The FDA recently approved Bristol Myers Squibb’s Opdivo, which is used in conjunction with platinum-doublet chemotherapy, for use in resectable NSCLC before surgery, in the neoadjuvant setting.

Baynes acknowledged Opdivo’s improved outcomes as a neoadjuvant therapy, but he also noted that neoadjuvant treatment is uncommon in NSCLC.

Baynes explained that in the current paradigm, a patient diagnosed with early NSCLC is usually taken straight to surgery under the care of a cardiothoracic surgeon, whereas neoadjuvant therapy takes two to three months before surgery.

Following surgery, the patient is transferred to a medical oncologist who is more likely to be familiar with the use of drugs such as PD-1 inhibitors.

Merck is also investigating the use of Keytruda as a neoadjuvant. In the phase 3 Keynote-671 trial, patients with stage II to IIIB NSCLC are given a neoadjuvant combination of Keytruda and chemo, followed by adjuvant Keytruda.

BMS is conducting a similar study for Opdivo called CheckMate-77T.

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