BARCELONA—Bladder cancer is a “difficult malignancy.” That’s how Alan Sandler, Roche SVP of oncology product development, prefaced his comments about new data showing Tecentriq plus chemo outpaced chemo alone—but only just.
“It’s a very difficult tumor to treat,” Sandler said. And no one knows this better than Roche, which managed to hang onto its accelerated bladder cancer nod for solo Tecentriq despite a phase 3 shortfall.
So the fact that the IMvigor 130 trial came up positive at all—cutting the risk of disease progression or death by 18% in previously untreated patients with metastatic disease, regardless of PD-L1 biomarker status—was something to cheer about, Roche figures. After all, this is the first time a checkpoint inhibitor combo has managed to fend off bladder cancer in phase 3, Sandler said.
Enough to be encouraging, perhaps. Enough for approval? Roche will be talking to regulators. But one of ESMO’s experts, Ignacio Durán, M.D., of the Hospital Universitario Marques de Valdecilla-IDIVAL in Spain, isn’t sure the numbers will stand up. This level of improvement in progression-free survival may not be enough for approval at this stage, Durán added.
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The 1,213-patient trial tested the Tecentriq-chemo combo and Tecentriq monotherapy against solo chemotherapy. After almost a year of follow-up, the combo patients had lived progression-free for 8.2 months, compared with chemo patients’ 6.3 months. The difference was statistically significant, checking the box for one of the trial’s two primary endpoints.
The other primary goal, overall survival for Tecentriq monotherapy versus chemo, isn’t yet ready for a final analysis, but Sandler called the trend “encouraging,” particularly for the group who tested positive for the PD-L1 biomarker. At the interim analysis mark, solo Tecentriq patients had lived a median 15.7 months after therapy compared with 13.1 months among the chemo patients.
Durán dug into the data to highlight stats he considered most promising: The number of complete responses, in which a patient’s tumors shrink to invisibility, or nearly so, was two times as high for the Tecentriq combo. FIfty-six patients taking the combo, or 13%, turned up a complete response, compared with 27 (7%) for chemo alone, the study showed.
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The trial will continue and definite overall survival numbers are yet to come. At an interim look, the study showed Tecentriq-plus-chemo patients lived 16 months compared with 13.4 months in the chemo-only arm. The hazard ratio indicated a reduction in the risk of death of 18%, but at this point, that’s an indicator, not a mature stat.
“Overall survival data continue to mature," Sandler said. "Actually, it was pretty close to being positive, just missed out. ... We look forward to seeing the data on overall survival when it matures."
The IMvigor study's also looking at Tecentriq monotherapy survival, though Roche hasn't been able to dig much into those numbers yet. If any data on overall survival prove to be positive—not a given, particularly with Tecentriq’s previous failure to prolong patients’ lives in a phase 3 trial—that would be a vindication for Roche and perhaps grounds for a full bladder cancer approval, rather than the conditional one it now bears.
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If overall survival bears out for the combo specifically? Gold-standard confirmation that the duo really does work better than this narrow positive suggests.
And if Roche is able to parlay the IMvigor 130 data into a new chemo-combo indication, that would give it a new lead in the immune-oncology market. Five of six drugs in the class boast a bladder cancer nod, and sales in that indication fall far short of the numbers in other cancers.
In the meantime, Roche will be looking to capitalize on its bladder cancer edge with four other phase 3 tests for Tecentriq, both alone and in combination with other medicines. The trials span early to advanced bladder cancer.