- Adding Roche's checkpoint inhibitor Tecentriq to standard chemotherapy extended median overall survival in patients with small-cell lung cancer (SCLC) by two months compared to chemotherapy alone, according to updated study results released Tuesday at the World Conference on Lung Cancer in Toronto.
- While Tecentriq posted only a modest gain in survival, SCLC has seen fewer advances than the more common non-small cell type. Typically, median survival is only 10 months with etoposide and platinum chemotherapy, the current standard of care.
- Bristol-Myers Squibb recently won approval for its immunotherapy Opdivo in third-line SCLC. Tecentriq, however, looks to be out in front for potential use in previously untreated patients. Roche has previously said it would submit the Phase 3 data to health authorities for approval.
Keytruda (pembrolizumab) and Opdivo (nivolumab) have rapidly altered treatment in non-small cell lung cancer (NSCLC), which accounts for about 85% of all lung cancer cases.
SCLC, however, has proved more intractable. Bristol-Myers previously fell short of the main goal of a Phase 3 study for its other immunotherapy Yervoy (ipilimumab) in first-line treatment of small cell. And Keytruda failed to best historical controls in a single-arm Phase 2 trial.
That made Roche's success with its Phase 3 study IMpower-133 a first, giving the Swiss pharma a rare competitive advantage in immuno-oncology. Both Merck & Co., Bristol-Myers and AstraZeneca have other efforts underway, however, meaning Roche's window of opportunity is limited.
Select immunotherapy trials in small cell lung cancer
|Study drug||Comparator||Treatment line||# of pts.||Status|
|CheckMate-032||Opdivo||N/A||3rd||109||Approved Aug. 2018|
|IMpower-133||Tecentriq||Chemo||1st||403||PFS, OS hit in June|
|Keynote-604||Keytruda||Chemo||1st||430||Primary completion in Jan. 2019|
|CheckMate-451||Opdivo, Opdivo + Yervoy||Placebo||Maintenance after platinum chemo||940||Primary completion in Sept. 2018|
|CheckMate-331||Opdivo||Chemo||2nd||568||Primary completion in Aug. 2018|
|Caspian||Imfinzi + tremelimumab + chemo||Chemo||1st||984||Data expected in 2019|
SOURCE: Companies, clinicaltrials.gov
Overall survival results for Tecentriq (atezolizumab), therefore, will likely be used as a rough yardstick for future competitors — although comparing trials in immuno-oncology is particularly tricky.
One year after treatment, slightly more than half of patients given Tecentriq on top of chemotherapy in IMpower-133 were alive, compared to 38% in the just chemotherapy arm.
Tecentriq also didn't appear to increase treatment toxicity much, with similar rates of hematologic side effects and Grade 3 or 4 adverse events — a point in favor for any combination treatment that bolsters efficacy.
Interestingly, however, benefit didn't appear to correlate with a biomarker called tumor mutation burden. Roche and other drugmakers have explored TMB as an alternative means of determining which patients might benefit most from immunotherapy.
One possible explanation could be the myelosuppresive nature of the chemotherapy combo regimen, researchers wrote in a New England Journal of Medicine article published Tuesday.
Also at the lung cancer conference, Roche reported survival results Monday from its IMpower-132 study of a combo of Tecentriq and chemotherapy in first-line non-squamous NSCLC. Data showed a 54% reduction in the relative risk of death over chemotherapy alone.
The Swiss pharma recently had review of another Tecentriq combo pushed back three months by the Food and Drug Administration, however, delaying when it might be able to challenge Merck in first-line NSCLC.