Merck & Co’s Keytruda and Bristol-Myers Squibb’s Opdivo might have been the first two immuno-oncology agents to reach the lung cancer market, but Roche’s atezolizumab looks to be close behind, and with strong early first-line data.
On Sunday at the European Cancer Congress in Vienna the Swiss group gave a first look at data for its project in first-line treatment of non-small cell lung cancer, presenting a 26% overall response rate for recently diagnosed patients and high expression of the immunological target. With final data in second and third-line treatment showing a nearly three-month survival benefit over docetaxel, Roche will be taking a persuasive case to regulators.
Opdivo has already received regulators’ backing for lung cancer treatment in Europe, and awaits a final sign-off within weeks; a US decision is due in early 2016. Keytruda will jump from the gates even sooner in the US, with a decision date by the end of this week.
Roche has yet to secure approval in any indication for atezolizumab. Bladder cancer was its early emphasis, but it is putting on an extensive programme in lung cancer, and all of its 2020 sales – $2.6bn – are attributed to this indication.
This is less than the $4.5bn forecast for Opdivo and $3.1bn for Keytruda, according to EvaluatePharma. Thus Roche is keen to show a competitive profile, and delivering strong first-line data to regulators and oncologists could perhaps improve its position when it launches.
The Roche data are also important since they suggest that blocking PD-L1 is no worse than blocking PD-1. Azetolizumab is an anti-PD-L1 MAb, while Opdivo and Keytruda both hit PD-1; AstraZeneca and Pfizer, which both have development-stage anti-PD-L1 assets, will have taken note.
Seeing the forest for the trees
The phase II Birch trial was a single-arm test of atezolizumab in first through third-line treatment as a monotherapy, a treatment protocol that might not be endorsed on a first pass by regulators.
Nevertheless, in first-line treatment atezolizumab showed efficacy, achieving a 26% overall response rate in those patients whose tumours have a high expression of the PD-L1 ligand that serves as a “switch” that turns off T cells’ immune response. In that subset of high PD-L1-expressing patients, in second line the response rate was 24% and in third line 27%.
Survival data are immature in this trial, although in the high-expressing population investigators measured a 14-month overall survival in first line patients and an 82% six-month survival rate. At six months the survival in second-line patients was 76%, and in third line 71%.
Roche’s presentation at ECC was the first peek at the Birch data it has offered to oncologists – the group had announced that it had met the primary endpoint of objective response rate in an August press release that described Birch as a pivotal trial.
Meanwhile, at Asco Roche had published some interim data from the Poplar trial of patients in second- and third-line use against docetaxel. ECC was an opportunity to release the primary overall survival analysis.
In all comers, the overall survival benefit for atezolizumab was 12.6 months to 9.7 months for docetaxel; the hazard ratio of 0.73 had a p value of 0.040, showing statistical significance, but not a high level. The population of high PD-L1-expressing patients had a greater survival benefit, exceeding 15 months.
This looks extremely similar to the findings from the Checkmate 057 trial of Opdivo, down to an equal hazard ratio of 0.73 for both. So said Dr Luis Paz-Ares, who presented those Opdivo data at Asco this year, in a discussion of the Poplar trial at the ECC – though he did point out that the BMS drug displayed a higher degree of statistical significance.
With a delay of about one year to make up versus Opdivo and Keytruda in lung cancer, it is no wonder that Roche is enthusiastic about its first-line data. A chance to strike first, or at least on an even footing, with atezolizumab’s rivals in early treatment could be what it needs to improve its competitive outlook.