Nice try.
Headline: The floodgates have been opened for upfront targeted systemic treatment options for non-small cell lung cancer (NSCLC).
The Study: The phase 3 IMpower150 trial enrolled patients with chemo-naive metastatic NSCLC with any or no PD-L1 expression, and it ended up being no expression in about half. Even EGFR- and/or ALK-aberrations (n=162) were allowed (kind of...you’ll see in a minute) if they failed at least one first-line TKI. All patients were assigned to carbo/taxol x 4-6 cycles plus one of three randomized therapies to continue until disease progression: [1] atezolizumab (aka Tecentriq), [2] bevacizumab (aka Avastin), or [3] atezo + bev. To match the number of arms, there were three primary endpoints: [1] progression free survival (PFS) for those with EGFR-/ALK-wildtype (WT) disease (n=1040), [2] PFS for those with WT disease and high gene expression of effector T cells (Teff, n=445), and [3] overall (OS) among those with WT disease. The tricky(est) part was that they had a finite p-value with a lot to spend it on. So this first report is strictly on comparisons between arms 2 and 3, the additions of atezo versus atezo + bev, and strictly among the populations as above. The big reveal: among the <700 patients analyzed, the addition of atezo to carbo/taxol/bev “significantly” improved PFS from 7 → 8 months (7 → 11 months among the few with high Teff), and it improved OS from 15 → 19 months.
Bottom Line: Golf clap for Genentech trying to create a new and...what’s the word we’re looking for, not improved...oh yeah, “convoluted” upfront systemic therapy option for NSCLC that includes not only chemo but also atezolizumab and bevacizumab. Truly nice try, but single agent inhibition of the PD-1 axis will probably do the trick. | Socinski, N Engl J Med 2018
The Study: The phase 3 IMpower150 trial enrolled patients with chemo-naive metastatic NSCLC with any or no PD-L1 expression, and it ended up being no expression in about half. Even EGFR- and/or ALK-aberrations (n=162) were allowed (kind of...you’ll see in a minute) if they failed at least one first-line TKI. All patients were assigned to carbo/taxol x 4-6 cycles plus one of three randomized therapies to continue until disease progression: [1] atezolizumab (aka Tecentriq), [2] bevacizumab (aka Avastin), or [3] atezo + bev. To match the number of arms, there were three primary endpoints: [1] progression free survival (PFS) for those with EGFR-/ALK-wildtype (WT) disease (n=1040), [2] PFS for those with WT disease and high gene expression of effector T cells (Teff, n=445), and [3] overall (OS) among those with WT disease. The tricky(est) part was that they had a finite p-value with a lot to spend it on. So this first report is strictly on comparisons between arms 2 and 3, the additions of atezo versus atezo + bev, and strictly among the populations as above. The big reveal: among the <700 patients analyzed, the addition of atezo to carbo/taxol/bev “significantly” improved PFS from 7 → 8 months (7 → 11 months among the few with high Teff), and it improved OS from 15 → 19 months.
Bottom Line: Golf clap for Genentech trying to create a new and...what’s the word we’re looking for, not improved...oh yeah, “convoluted” upfront systemic therapy option for NSCLC that includes not only chemo but also atezolizumab and bevacizumab. Truly nice try, but single agent inhibition of the PD-1 axis will probably do the trick. | Socinski, N Engl J Med 2018
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