ASCO: Roche’s Tecentriq grabs I-O’s first win in post-surgery lung cancer, but it’s limitedand an FDA approval could be, too – FiercePharma

In early cancer thats amenable to surgery, a field viewed as the next battleground for PD-1/L1 immunotherapies, Roches Tecentriq has claimed the first post-operative win innon-small cell lung cancer. But the drugs role, at least in some patients, remains unclear.

Tecentriq slashed the risk of cancer recurrence or death after surgery by 34% in a studyslated for the virtual American Society of Clinical Oncology meeting next monthbut onlyin patients with stage II to IIIA disease whose tumors bore the PD-L1 biomarker.

Charles Fuchs, M.D., head of oncology andhematology product development at Roches Genentech, called the win a transformative step in helping patients with early-stage lung cancer.

Historically, improving a disease-free survival by 20% or 30% has been practice-changing and really meaningful when youre talking in a curative setting, Fuchs said in an interview.

But when all patients in the IMpower010 studyare counted, the number drops to 19%raising questions about how broad an FDA approval might be and whether doctors would actually use the drug for post-surgeryNSCLC.

Plus, the 34% recurrence reduction rate Tecentriq achieved in the carved-out subgroup was way lower than the 83% AstraZenecas small-molecule drug Tagrisso accomplished in patients with EGFR-mutated stage II to IIIA disease in its own phase 3 Adaura trial.

While Tagrisso targets a niche population, physicians are benchmarking their interest in Tecentriqs post-surgery adjuvant use against the EGFR inhibitor data right now, becausedata hasntyet shownwhether either drug can help patients live longer.

RELATED:Roche's Tecentriq is the first I-O drug to claim a post-surgery win in lung cancer. But will doctors use it?

Fuchs acknowledged the field is evolving but stressed that Tagrissos impressive showing was in a small subset of patients, whereas PD-L1-positive disease makes up 40% to 50% of all NSCLC cases. So he called Tecentriqs 34% improvement as clinically meaningful and practice-changing.

The next question centers onTecentriqs benefit for PD-L1-negative patients. When those trial subjects were counted, Tecentriqs reduction of disease recurrence dropped to 21%, which is still statistically significant. Butthe rate fell below the statistical significance bar to 19% once all randomized patients, including those with stage IB disease, were included.

Fuchs suggests that data from the stage IB patientswho made up 12% of the total trial populationare immature at the interim analysis because those patients are healthier;it takes longer for that group to accrue recurrence cases.

RELATED:AstraZeneca's blockbuster Tagrisso gets major boost with FDA OK for early lung cancer use

During Roches first-quarter earnings call a few weeks ago, Roches pharma chief Bill Anderson put the size of the market for resectable lung cancer at between $2 billion and $3 billion. But he also acknowledged the uncertainty of whether Tecentriq is for only PD-L1-positive patients or for all patients. He said he expectsmore mature disease-free survival data to answer that question.

Roche isnow talking to the FDA and the European Medicines Agency to see what we collectively think is in the best interest of patients in terms of a potential label for Tecentriqs NSCLC adjuvant use, Fuchs said.

As Roche awaits key life extension data from the IMpower010 trial, a recent survey by Jefferies analyst Peter Welford suggested that almost all physicians would rather wait until that data emerge to consider using a PD-1/L1 therapy in that group.

One reason for caution is the uncertainty of whether PD-1/L1 inhibitors will work in metastatic cancer patients who were treatedwith one of the drugs early on. Its possible that physicians might reserve PD-1/L1 for more advanced disease; Mercks PD-1 inhibitor Keytruda combined with chemo has become the standard of care for front-line treatment of metastatic disease because its proven to help patients live longer.

The question of sequential PD-1/L1 use needs to be addressed, Fuchs said, but he stressed the importance of advancing the landscape of cancer immunotherapy beyond the PD-1/L1s.

Meanwhile, other PD-1/L1 players are also targeting adjuvant NSCLC. These include Ketyrudas Keynote-091 trial, which is expected to deliver data later this year.

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ASCO: Roche's Tecentriq grabs I-O's first win in post-surgery lung cancer, but it's limitedand an FDA approval could be, too - FiercePharma