- Roche's checkpoint inhibitor Tecentriq got approval Thursday from the Food and Drug Administration in the first-line setting to treat non-squamous non-small cell lung cancer in combination with Avastin and chemotherapy.
- The regulatory OK helps Tecentriq catch up to Merck & Co.'s Keytruda, which last May gained approval in combination with pemetrexed and carboplatin for the first-line treatment of metastatic non-squamous NSCLC regardless of PD-L1 expression. While a positive step for Roche's I/O ambitions, the label expansion doesn't include patients with EGFR or ALK mutations — a population that could have helped set Tecentriq apart from Keytruda and secure more market share.
- Roche also noted that it is working with the FDA "to better understand and characterize the potential effects" of anti-drug and neutralizing antibodies related to the therapy.
The FDA approval for Tecentriq (atezolizumab) extends the PD-L1-blocking antibody's use into the first-line setting for a majority of lung cancer patients. About 85% of lung cancer cases are NSCLC, and the approval covers patients regardless of PD-L1 expression level who do not have EGFR or ALK mutations.
Merck's Keytruda (pembrolizumab) first picked up an accelerated approval for a comparable indication more than a year and a half ago. Now, Roche can compete in that arena too with Tecentriq.
But in a game of catch-up for Roche, an approval that differentiated Tecentriq from Keytruda would have been helpful to significantly shake up market share.
Keytruda still stands alone as an approved single agent for patients with high PD-L1 expression levels in the first-line setting for metastatic NSCLC without EGFR or ALK mutations. The other main rival in NSCLC is Bristol-Myers Squibb's Opdivo (nivolumab), however that drug has faced challenges in locking down a first-line approval.
Keytruda's label advantages have translated into better market share and sales. Through the first nine months of 2018, Keytruda posted global net sales of $5.0 billion, while Opdivo netted $4.9 billion and Tecentriq was at $528 million.
Roche's approval was based on IMpower 150, a Phase 3 trial that tested a combination of Tecentriq, Avastin (bevacizumab) and chemotherapy against two other arms of Avastin plus chemotherapy and Tecentriq plus chemotherapy.
Patients taking the regimen with Tecentriq plus Avastin lived longer, with a median overall survival time of roughly 19 months instead of 15 months.
Some subgroup analyses suggested the pharma could have been eyeing a first-line approval regardless of EGFR or ALK mutations as well, which would have set the therapy apart from Keytruda.
In a New England Journal of Medicine article published in June, the study's authors found in an exploratory analysis that patients with these mutations showed a median progression-free survival time of roughly 10 months instead of 6 months on Avastin plus chemotherapy.
Yet, the approval excludes patients with these genomic tumor aberrations despite them being in the intent-to-treat population of the study.
"Maybe I'm missing something, but why is the new approval of carbo/pac/bev/atezolizumab for nonsquamous NSCLC specifically excluding EGFR and ALK when those were the [patients] we were most excited about benefiting in IMpower150?" Nathan Pennell, director of the Cleveland Clinic's lung cancer program, tweeted Thursday.
A further challenge and potential complication to watch for Roche will be on how its post-marketing commitments with the FDA materialize. The company stated it will focus on understanding and characterizing anti-drug antibodies and neutralizing antibodies related to Tecentriq.
Still, the label update is surely welcome for Roche given a recent delay. The company had to wait an additional three months for this approval after the FDA decided in September to hold off on a final decision to review a "major amendment" to the filing.