Roche ushers early lung cancer into immunotherapy era with Tecentriq FDA approval. Will doctors follow?

Roche’s Tecentriq has ushered in a new era, offering the first immunotherapy option for non-small cell lung cancer (NSCLC) patients right after tumor surgery. But doctors appear reluctant to use it for now, at least for some patients.

The FDA has greenlighted Tecentriq and platinum-based chemotherapy as post-surgery treatment for NSCLC with expression of the PD-L1 biomarker covering at least 1% of tumor cells. Friday’s approval inducts Tecentriq as the first PD-1/L1 inhibitor for the so-called adjuvant treatment of NSCLC to prevent cancer from returning and therefore potentially cure a patient.

Roche’s pharma chief, Bill Anderson, has previously pegged the size of the market for resectable NSCLC at $2 billion to $3 billion. However, despite the landmark nature of the FDA go-ahead, it’s uncertain how much share Tecentriq can carve out. Doctors have questioned its benefit in a patient subgroup and its ability to help patients live longer.

Tecentriq earned its new approval with data from the phase 3 IMpower010 trial. At an interim analysis, adding Tecentriq after surgery and adjuvant chemo cut the risk of disease recurrence or death by 34% in patients with stage 2 to 3A NSCLC whose tumors expressed PD-L1 at 1% or above, according to results unveiled at the American Society of Clinical Oncology's 2021 meeting.

The improvement was “practice-changing,” Charles Fuchs, M.D., head of oncology and hematology product development at Roche’s Genentech, said at the time. About half of NSCLC cases are diagnosed early with stage 1 to stage 3 disease, and about half of them still see their cancer come back after surgery, according to Roche.

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The trial did include PD-L1-negative patients, but Tecentriq didn’t show a benefit there. And data among patients with stage 1B disease were immature. So Roche filed the stage 2 to 3A, PD-L1-positive group with the FDA and landed a priority review in early August.

But additional data shared in September at the European Society of Medical Oncology's (ESMO's) 2021 event called into question Tecentriq’s use in patients with PD-L1 expression between 1% and 49%. The study wasn’t designed to evaluate that population, but a subgroup analysis showed that the Roche drug only pared down the risk of recurrence or death by 13% in those PD-L1-low patients. Even after removing EGFR- or ALK-positive patients—who arguably are more suited for targeted therapy—the reduction was not impressive, at 18%.

During a discussion at ESMO 2021, several panelists from European medical organizations voiced skepticism about Tecentriq’s adjuvant use in patients with PD-L1 below 50% as they noted that Tecentriq’s benefit appears to be mainly for the PD-L1-high group.

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Besides the biomarker limitation, Benjamin Besse, M.D., chair of the European Organization for Research and Treatment of Cancer (EORTC), also said he would like to see longer-term data. Tecentriq showed a benefit in stalling relapse, “but we need to cure more; we don’t need just to delay recurrence,” he said during a presentation about IMpower010.

The situation won’t be much different in the U.S., SVB Leerink analyst Daina Graybosch, Ph.D., said in a recent interview. “In the U.S., even it’s approved in greater than 1%, I got the feeling that there’ll be a lot of debate and docs won’t immediately use it in the 1% to 49% PD-L1,” she said. “They are just very looking forward to more data from basically better PD-1s.”

A survey Jefferies conducted ahead of Roche’s IMpower010 readout showed that 24 of 25 oncologists treating NSCLC in the U.S. said they wouldn’t consider using a PD-1/L1 therapy for adjuvant treatment of early NSCLC based only on the disease-free survival marker. They want to see the gold-standard life extension data.

A “world pre-eminent lung cancer expert” also suggested that most doctors would wait for the overall survival data unless the disease recurrence results turned out to be similarly striking to the 83% risk reduction AstraZeneca’s Tagrisso recently showed in EGFR-mutant disease, Jefferies analyst Peter Welford wrote in a March note. In an exploratory analysis of the PD-L1 50% or above group in IMpower010, Tecentriq reduced the risk of disease recurrence or death by 57% in stage 2 to 3A NSCLC.

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Even when doctors eventually start widely using PD-1/L1 inhibitors for adjuvant NSCLC, over a third of doctors Jefferies polled said they would reach for Merck’s Keytruda, while less than 10% chose Tecentriq.

Both Besse and Graybosch noted that Tecentriq’s PD-1/L1 rivals are expecting adjuvant NSCLC data soon. Most notably, Keytruda’s phase 3 KEYNOTE-091 trial, also known as PEARLS—which Merck’s running in collaboration with EORTC—will read out next year. The phase 3 ANVIL study by the National Cancer Institute could also report data for Bristol Myers Squibb’s Opdivo in the same setting around next year.

“We will have a massive number of new patients treated, so I think at the end we will decide probably not based on this one,” Besse said of IMpower010.