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HER2 as a New Target in NSCLC


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HER2 as a New Target in NSCLC: Common Enough, Effective Enough to be Paid For?

August 17th, 2013 - by Dr. Jack West

A new report published in the Journal of Clinical Oncology reports that HER2/neu (HER2) mutations are seen in 1.7% of patients with non-small cell lung cancer and that HER2 inhibitors may be an effective treatment, at least transiently, for many of these patients. But is this enough to make HER2 mutations a practical target? How are we going to address a growing list of very uncommon and relatively understudied potential targets? What if insurers are unwilling to pay for them?

To dig a little deeper in the paper, it comes from multiple centers in France, Switzerland and Spain, collaborating to test 3800 patients with NSCLC, early or later stage. Altogether, 65 patients, or 1.7%, were found to have a HER2 mutation (mutation in the HER2 gene, as opposed to the potentially more common but perhaps less relevant finding of over-expression of the HER2 protein). Interestingly, this group was comprised entirely of patients with adenocarcinomas and was disproportionately women (45:20, 69%) and never-smokers (52%). In all but one case, HER2 was the only “driver” mutation identified, so patients didn’t also have an EGFR mutation, ALK rearrangement, etc.

Within that group of 65 patients, 33 had stage IV disease, and 16 of them received at least one HER2 inhibitor therapy along with standard chemotherapy, and a few received more than one over several lines of treatment. Altogether, 22 different cases of anti-HER2 therapy were given to stage IV patients, and partial responses (PRs) were seen to 11 of them, for a PR rate of 50%, with 7 showing stable disease (SD, 32%) and progressive disease (PD) in 4 cases (18%). In most cases, particularly with Herceptin (trastuzumab), this treatment was given along with standard chemotherapy.The median duration of progression-free survival (PFS) in patients receiving first-line anti-HER2 therapy was 5.1 months.

Taking a step back, we need to ask what this really means. While seeing responses to anti-HER2 therapy in patients with a HER2 mutation is very promising, it’s worth noting that in most cases this was given with chemotherapy, and the response rate to chemotherapy is 20-35% in most trials. Moreover, the median PFS of 5.1 months isn’t remarkably promising compared to the PFS of other targeted therapies like EGFR TKIs for people with an EGFR mutation or XALKORI (crizotinib) for those with an ALK rearrangement, in whom we expect to see a median PFS of 9-13 months, and we routinely see a median PFS of 3-5 months with standard chemotherapy.

So once the smoke clears and we recognize that these results are not in and of themselves especially remarkable, we’re left with the question of whether HER2 testing should be commonplace or standard, and whether anti-HER2 therapies like Herceptin should be regularly administered to the 1-2% of patients who are found to have a HER2 mutation. As exciting as the concept of more targets and targeted therapies is, I think many (most?) insurers will be disinclined to pay for testing or for the treatments that may have some modest benefit but are not well studied and are clearly not yet considered a standard of care. Even if covered to some degree, I can envision insurers saying that for such an unproven therapy, a patient may be responsible for a significant fraction of the cost.

What do these results mean to you? If not covered, do you think these results are promising enough to pay for the testing or the anti-HER2 therapies like Herceptin, which can amount to many thousands of dollars per month? Or would you want to see further testing done to establish a clear benefit before HER2 becomes a more established treatment and routinely covered for the minority of patients who have a HER2 mutation?

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