Earlier this week, the FDA approved the oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) Tarceva (erlotinib) for the approximately 10% of advanced NSCLC patients with an activating EGFR mutation in North America and Europe (approximately 30% in Asia).   While that's generally a good thing, and it's in keeping with the evidence very strongly supporting erlotinib or another EGFR TKI as the optimal systemic therapy for patients with an activating EGFR mutation, the indication was paired with a positive result on a specific mutation test marketed by Roche called cobas and used in the EURTAC trial of Tarceva vs. chemo that was conducted in Europe on patients with an activating EGFR mutation on the Roche test that was approved to be paired with the first line Tarceva indication.

I'm concerned that this development may well be detrimental for patients, even if it's a shrewd move for Roche.  Why? Because there is already a clear consensus that EGFR TKI therapy is the preferred treatment for patients with an activating EGFR mutation, and the evidence supporting it is so overwhelmingly compelling that it's uncommon to have erlotinib refused by payers as the treatment of choice in EGFR TKI-naive patients, even before the official FDA approval.  Moreover, over the past 9 years since activating EGFR mutations were first identified, a wide range of different tests to detect them have been used.  We know that the excellent responses with EGFR TKIs are seen primarily in patients with the more common exon 19 and exon 21 mutations, which are the ones specifically detected with the cobas test from Roche, but many other testing platforms can do this quite well and have been used for years and years now to identify patients who are great candidates for early EGFR TKI therapy.  

By linking the indication for first line Tarceva in EGFR mutation-positive patients with a positive result on the cobas test, Roche may well have enforced a monopoly on molecular testing, but there is no reason to think that their test is meaningfully better than many other options.  To me, this move seems as crass and transparently commercial at the expense of good science and care as seeking an FDA approval that erlotinib needs to be taken daily with a venti Starbucks latte if Starbucks had wrangled their way into a strategic partnership and got written into the EURTAC protocol.  My fear is that many people who have had EGFR mutation testing done by other reputable sources will now have their opportunity to receive first line Tarceva jeopardized based on the linked approval of the indication with the test.  Some people may require additional biopsies and incur treatment delays, increased risks, and added costs just because Roche finagled an opportunistic rider on the science.

I have long been critical about afatinib, the "irreversible pan-HER inhibitor" from Boehringer-Ingelheim (BI) that is poised as a next generation EGFR inhibitor but actually has no real evidence that it's more than a more toxic version of Tarceva or Iressa (gefitinib) as first line therapy for patients with an activating EGFR mutation and advanced NSCLC, with no clear added benefit.  However, the LUX Lung 3 trial was conducted to conform to FDA gamesmanship and obtain a first line approval, and we anticipate that BI will win that approval.  I have historically favored Tarceva because I see no evidence of greater benefit but worse side effects with afatinib, and unless mandated by payers, I don't think we should reward gamesmanship that is about marketing rather than science.  While I'd generally be happy to now have an official approval of Tarceva as first line therapy for people with advanced NSCLC and an activating EGFR mutation, this linking of the approval to a Roche test isn't clearly better than what we have now, and it may well be inferior in many ways to "multiplex platforms" for broader molecular testing we hope to see more of in the next few years that would allow us to test for many relevant driver mutations at one time, with one sample.  My sense is that this strategy by Roche is a commercially driven move that is a race to the bottom, bad for patients and for the science, and it represents a low point that underscores that when they purchased their partnership with Genentech, they diluted and sold away the soul and scientific credibility that the latter company had previously earned over time.