Roche’s Tecentriq looks on track to become the first immunotherapy to be approved for the perioperative treatment of non-small cell lung cancer, data from the adjuvant study Impower-010 just unveiled at the virtual Asco meeting suggest.
But the victory will be tempered by the fact that the disease-free survival (DFS) advantage seen in all-comers was clearly driven by patients expressing PD-L1. “The benefit ... seems to be in those patients who do have PD-L1 expression, and not in those who do not,” said Impower-010’s lead author, Dr Heather Wakelee of Stanford University School of Medicine.
The result will shape Roche’s filing strategy, the precise details of which remain confidential, and the available market. When Impower-010 was toplined positive in March the Swiss group said it would “submit these data to regulatory authorities as soon as possible”.
And there is further nuance to the result, beyond the question of patients’ PD-L1 positivity. Impower-010 has a sequential analysis, enrolling stage IB-IIIA NSCLC patients in the adjuvant setting, but initially analysing DFS only in the stage II-IIIA population – first in PD-L1 ≥1% expressers, and then in all randomised subjects.
It was these two analyses that the Asco data relate to, explained Dr Wakelee on an embargoed press call before the Impower-010 data were formally unveiled today. And, in PD-L1 expressers, the two-year DFS rate was 74.6% for Tecentriq versus 61.0% for best supportive care.
The median value has not yet been reached, but the overall risk of disease recurrence was reduced by 34% with Tecentriq, with a statistically significant p value of 0.004.
Tecentriq also showed a 21% benefit irrespective of PD-L1 expression in the stage II-IIIA population, and with p=0.02 this too crossed the boundary for statistical significance. However, “the vast majority of benefit seemed to be in those patients who did have expression of PD-L1 on their tumours”, said Dr Wakelee.
She will present the results specifically in PD-L1-negative patients at Asco on Sunday June 6, but the strong hint is that there is no difference in DFS here between Tecentriq and best supportive care.
Should Tecentriq in this setting be approved only in PD-L1 expressers, diagnosing patients’ PD-L1 status could imply an additional burden to therapy, though genetic and biomarker analyses are now commonplace. More important for Roche is that it would cut the available market, possibly by a half.
And whether the stage IB population is in play is a separate question. Only 121 of Impower-010’s 1,005-strong population had stage IB disease, and in general these patients “tend to do better”, said Dr Wakelee.
The next analysis in the Impower-010 hierarchy will look at DFS in all-comers, including the IB patients, followed by overall survival in all-comers. At present the 12-month DFS rate in all-comers is running at 71.4% versus 63.6%, and is not yet sufficiently mature for a formal analysis.
Still, even a slice of the adjuvant NSCLC market would give Tecentriq an important head-start on its anti-PD-(L)1 competition. Adjuvant/neoadjuvant settings are becoming key for immunotherapies, and Keytruda and Opdivo have struck blows this year with wins in adjuvant renal cancer and adjuvant bladder cancer respectively.
Success has been harder to come by for Tecentriq, which failed in neoadjuvant triple-negative breast cancer and adjuvant urothelial carcinoma before registering a positive result in the perioperative TNBC Impassion-031 trial, albeit on pathological complete response, likely not an approvable endpoint.
At least there is little doubt on this score in Impower-010: DFS is precisely the endpoint on which Astrazeneca’s Tagrisso gained its adjuvant use label in EGFR-positive NSCLC last December.
This story has been corrected to reflect the fact that the stage II-IIIA all-comers analysis was statistically significant.