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Pivotal Phase III Study Shows Roche’s Tecentriq Helped People With Early Lung Cancer Live Longer Without Their Disease Returning

(Roche) Mar 22, 2021 - Roche today announced that the Phase III IMpower010 study evaluating Tecentriq® (atezolizumab), compared with best supportive care (BSC), met its primary endpoint of disease-free survival (DFS) at the interim analysis. Tecentriq showed a statistically significant improvement in DFS as adjuvant therapy following surgery and chemotherapy in all randomised Stage II-IIIA populations with non-small cell lung cancer (NSCLC). The magnitude of DFS benefit was particularly pronounced in the PD-L1-positive population.

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H. Jack West, MD (Posted: March 22, 2021)

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This is the first of likely several trials of adjuvant/neoadjuvant immunotherapy that will prove to be positive based on a surrogate endpoint, but here we have learned that it's especially favorable in those with PD-L1 positive cancers (which is the positive spin on "it was decidedly unimpressive in patients with PD-L1 negative cancers"), and with it reaching statistical significance for DFS on an interim analysis and no reported OS results, I suspect that we'll be left debating 1) whether statistical significance should imply clinical significance, 2) whether a DFS benefit that I'm going to predict is far less impressive than the HR of 0.17 seen for DFS on ADAURA should lead to a change in practice without seeing an improvement in OS, and 3) whether we should exclude patients who have PD-L1 <1% who (for the sake of argument I'll predict) show no meaningful improvement in DFS, let alone OS, with adjuvant atezolizumab.

On top of this, we'll have room to debate whether FDA's shift to a mindset of providing the most liberal path to approval that can possibly be justified, not really filtering for clinically significant benefit, and then abrogating any responsibility for difficult judgment on appropriate use in practice to rank and file clinicians who won't have time or ability to focus on careful assessment of the data beyond being detailed by pharma reps. Also, we'll need to factor in not only the very significant financial cost of prolonged immunotherapy but the real risk of chronic, even permanent, treatment-induced toxicities from immunotherapy in patients who have a significant chance of already being cured from the treatments they'd have already received.

I suspect that the results of this trial will compare unfavorably to the magnitude of benefit in terms of DFS that we saw with adjuvant osimertinib in the ADAURA trial, and this will lead to refinement of our question of how much we should focus on DFS and other surrogate endpoints like pathologic complete response rates as sufficient to change our practice, especially when "statistical significance" does not necessarily imply clinical significance.

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Tomasz M. Beer, MD, FACP

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