Merck details Keytruda's postsurgery lung cancer win, teeing up fight against Roche's Tecentriq

Merck has laid out the specific data for Keytruda in early-stage lung cancer, with signs of an upper hand against 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 results from the phase 3 Keynote-091 trial, also known as PEARLS, at a European Society for Medical Oncology (ESMO) plenary session Thursday.

Since Merck revealed the headline win in January, industry watchers have been banking their optimism on what looks like an advantage over Roche’s Tecentriq, which last October became the first immuno-oncology agent approved in the adjuvant NSCLC setting. Tecentriq’s nod, however, 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 with Fierce Pharma.

Given Tecentriq’s limitation, the key question is on how Keytruda fared in patient subgroups, especially in those with stage IB or PD-L1-negative disease. Previously, in the IMpower010 study, Tecentriq delivered a disease-free survival improvement of 19% in adjuvant NSCLC or 34% when stage IB and PD-L1-negative patients were excluded.

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

Specifically, in patients with stage IB disease, Keytruda pared down the risk of disease recurrence or death by 24% over placebo, according to the presentation at ESMO Plenary. And in PD-L1-negative patients, the number was 22%.

But in a surprising dataset that Merck had previously announced, Keytruda only showed an 18% disease-free survival benefit in patients with PD-L1 expression at 50% and above. The trial has therefore not met one of its dual primary endpoints at this point.

The Keytruda data is at odds with Tecentriq’s. In Tecentriq’s study, among stage II to IIIA patients, the Roche PD-L1 inhibitor only posted a 13% disease-free survival advantage in those with PD-L1 expression between 1% and 49%, meaning it was really the PD-L1-high patients who were driving the 34% benefit in PD-L1 all comers.

Baynes attributed the miss to a relatively low number of disease recurrence or death in the PD-L1-high group. At the data cut off, 117 events had occurred in 333 PD-L1-high patients. Merck is hopeful that with longer follow-up, the PD-L1-high data will become significant, he said.

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%. “We’re optimistic about showing [a survival benefit] in the long term, but clearly, it’s too early to make any kind of survival claim at this point,” Baynes said.

Postoperative NSCLC represents a large market. About one in two NSCLC diagnoses presents with operable tumors, and despite surgery, about one out of every two patients will recur, according to Baynes.

There has also been debate over whether immuno-oncology agents should be used before or after surgery. A few days ago, the FDA approved Bristol Myers Squibb’s Opdivo, used alongside platinum-doublet chemotherapy, for use in resectable NSCLC before surgery, in the neoadjuvant setting.

Baynes acknowledged the improved outcomes Opdivo showed as a neoadjuvant therapy, but he noted that neoadjuvant treatment is not common in NSCLC.

In the current paradigm, a patient diagnosed with early NSCLC is usually taken right to surgery under the care of a cardiothoracic surgeon, Baynes explained, whereas neoadjuvant therapy takes about two to three months before surgery. After surgery, the patient is transferred to a medical oncologist who’s likely more familiar with using drugs like PD-1 inhibitors.

“It will require quite a lot of education and changing of practice to really make this an important addition,” Baynes said of using immunotherapy in neoadjuvant NSCLC.

Merck is also evaluating the neoadjuvant use of Keytruda. The phase 3 Keynote-671 trial explores the neoadjuvant combination of Keytruda and chemo, followed by adjuvant Keytruda in stage II to IIIB NSCLC. BMS has a very similar study dubbed CheckMate-77T for Opdivo.