Neratinib’s Approval is a Win for Puma, but not for Patients

Karuna JaggarBy Karuna Jaggar, Executive Director

Last week the FDA approved neratinib as a so-called “extended therapy” for early-stage HER2-positive (HER2+) breast cancer to be used after the standard of care, which includes surgery and treatment for a year with trastuzumab (brand name Herceptin). Despite the fact that neratinib comes with additional side effects and women treated with the drug have not been shown to live longer, Puma Biotechnology, Inc. is reportedly planning to sell the drug (brand name Nerlynx) for $10,500 a month.

Rather than marking a breakthrough in breast cancer treatment, the approval of neratinib marks an eroding of FDA standards. Puma received accelerated approval for neratinib based largely on a single phase III clinical trial, which showed that women with early stage HER2+ breast cancer were slightly less likely to experience a recurrence of their disease. But this minimal reduction came at a cost of high rates of severe diarrhea.

The ExteNET trial, which was the basis for the FDA’s approval, randomized 2,840 women to receive either neratinib or a placebo after receiving the standard of care (surgery plus a year of trastuzumab) for early-stage HER2+ breast cancer. Researchers hoped to lower the risk of disease returning after standard treatment and were able to show a minor improvement in  the length of time before a recurrence (what the researchers term “invasive disease-free survival”) by giving neratinib to patients who had completed treatment. More than nine in ten patients in the ExteNET trial, regardless whether they received the experimental treatment, did not have a breast cancer recurrence after two years: 91.6% of patients were free of disease after two years on the placebo group, compared to 93.9% on the neratinib group.

Neratinib’s ability to slightly reduce the risk of recurrence by half in just a month is not the same as showing that women live longer with treatment. A so-called “surrogate endpoint” like invasive disease free survival that is not clinically significant may be useful in guiding the development of experimental treatments, but it cannot replace the outcome that patients and doctors ultimately care about: women actually living longer, or at least living better with fewer side effects.

Meanwhile, 40% of patients taking neratinib experienced grade 3 diarrhea, which led 17% of patients to stop taking the experimental drug. Grade 3 diarrhea can require treatment in a hospital or clinic. With such severe side effects, and no demonstrated overall survival benefit, it is hard to justify adding neratinib to treatment protocols for a group of patients who are just as likely to do well with the existing standard of care. Survival rates for early stage HER2+ breast cancer patients are fairly high with current treatments, with 84% of patients with mostly node-positive disease living 10 years after treatment.

Often described as “controversial,” neratinib’s approval was viewed as a long shot by many journalists covering biotechnology who predicted that Puma’s request would not be approved by the FDA. After following fewer than 3,000 women for just two years, the drug has been shown to have a small possible benefit through a surrogate endpoint and comes with known toxicity. Neratinib’s approval is a win for Puma, but not for patients.

Desperately needed breakthroughs in treatment are all too rare. The last one for breast cancer was nearly twenty years ago in 1998, when the Food and Drug Administration (FDA) approved trastuzumab for use in women with metastatic HER2+ breast cancer. Several years later, the FDA also approved the use of trastuzumab for early-stage HER2+ breast cancer. Despite the risk of heart problems associated with the drug, trastuzumab can help reduce the risk of recurrence and death for the 20-30% of women diagnosed with this aggressive subtype of breast cancer.

Unfortunately, trastuzumab doesn’t always work for all patients, and some HER2+ breast tumors are either inherently resistant or develop resistance to trastuzumab. Researchers have attempted to overcome this barrier by combining treatments in an effort to block multiple pathways and prevent resistance through drugs like neratinib.

This landmark approval of a targeted therapy for a specific (HER2) cancer-related molecular marker sparked a lot of excitement that we are on the cusp of a new era of targeted life-saving therapies. But the reality is, subsequent drugs developed to treat breast cancer have not been shown to clearly benefit patients by extending overall survival or improving quality of life. And yet companies are selling these add-on treatments for well over $100,000/year.

At Breast Cancer Action, we believe the best way to ensure more truly breakthrough treatments is to incentivize innovative research by preserving approval standards. If drug companies know their treatments must do one of the following three things in order to get approved, they’ll focus on developing treatments that:

  • Help patients live longer (improving overall survival)
  • Help patients live better (reducing side effects and lowering toxicity)
  • Help people access treatment (lowering costs)

Too often, the FDA puts speed before safety and efficacy, allowing companies to sell drugs that have not been proven to do just one of these things to benefit patients. In recent years, a majority of cancer drugs have been approved by the FDA based on surrogate endpoints and follow up studies in subsequent years have shown that half of these do not help patients live longer.

With the approval of neratinib, the FDA has once again approved an experimental drug that has not been shown to lengthen or improve breast cancer patients’ lives—either by helping them live longer or live better, with fewer side effects. The decline of standards at the FDA over the last decade is alarming and means that thousands of cancer patients each year are exposed to expensive, toxic treatments that don’t actually help them live longer.

After two decades of waiting for the next breast cancer breakthrough, many of us in the breast cancer community are frustrated and fatigued. And the reality is we haven’t actually gotten a breakthrough by lowering approval standards. Instead of letting drug companies profit from our desperation, let’s call on the FDA to uphold high standards of safety and efficacy that incentivize true innovation.

This entry was posted in Articles, BCA News.

11 Responses to Neratinib’s Approval is a Win for Puma, but not for Patients

  • Laurie Davis says:

    I am taking Neratinib… I was diagnosed early stage had chemo, Then the Herceptin. A double mastectomy and multiple surgeries for reconstruction. Are you telling me that this medication is doing nothing for me? What about the blood/brain barrier block that I have been reading about.. This article is upsetting. My sister passed away from Breast cancer à few years ago. I have the side effects of the diarrhea and the extreme fatigue!!!!!!! And à few more side effects. Am I taking this medication for nothing? I had such high hopes for Neratinib, I am praying this article is not true. I have had pnemonia 6 time’s during my treatment and had double pneumonia 2 weeks ago and I have a fear I will get à reoccurrence in my lungs. I pray to God this medication works.

    • Kira Jones says:

      Thanks for taking the time to post a comment, Laurie. Through our free Information & Resource service, we provide unbiased information about breast cancer to anyone who needs it. Given the nature of your comment and the questions you posed, I’d encourage you to email our Resource Liaison Zoë Christopher at or give her a call at 415.243.9301, ext. 10. She can address your questions.

  • loretta says:

    Thank you for this article. These are my sentiments exactly. I am a desperate her2 pos patient who just completed what I was told I needed, and as I am about to finish herceptin I was told I needed this new drug.
    I am at their mercy , as I want to live , but I am leaning towards a definite no for this drug .
    It saddens me immensely, as they know we are in a position not to refuse anything that may help. Bless you

  • Laura towney says:

    Neratinib cleared my breast cancer in operable tumour in my right arm and extensive and aggressive subcutaneous skin mets in one month from the start of treatment. This drug gave me a miracle as I was bed ridden in severe pain and within such a short time I was again and resuming my life again. I also experienced no side effects at all

  • Jennifer says:

    It is a troubling article for me as well. I’m 43 had chemo, double mastectomy, radiation and was told by 2 Oncologists this could benefit me bc it passes through the brain, unlike herceptin and the data for someone who also is brca 2 positive supports the 3% additional recurrence protection.
    I feel this article about the cost with an unknown hidden agenda.

  • M.B. says:

    My mom had a breast cancer, had her surgery, chemotherapies, and started to feel herself again after everything. However, after the surgery and chemotherapy, she started taking Neratinib and she couldn’t eat anything, couldn’t move from her bed, and had diarrhea ALL THE TIME! It was even worse than before her surgery and when she was on chemotherapy. She was feeling so weak and horrible! She was loosing a lot of weight and was worried about her health and kidneys, because she was drinking a lot of water but that water did not go anywhere. She had to stop taking Neratinib because the side effects were so bad that there was really no point of going through all that bad stuff for supposedly around 2% higher chances of survival than without taking it. Is it really worth it if you feel like crap for one year and can’t do anything, go anywhere, and have to be “tied” to your bed the whole time? I just hope there will be something less toxic and a lot more helpful than Neratinib, because this “medicine” is horrible!

  • C.P. says:

    I am taking Nerlynx following Herceptin, Perjeta, Carboplatin, Taxotere. I was told I was patient #2 following FDA approval. Your article doesn’t give all the facts as certain subgroups get more benefit from Nerlyx than others. For example, hormone positive patients get more benefit than hormone negative.

    I have a teenager at home still and want to do everything I can to be there to guide him in to adulthood. Even though i had grade 3 diarrhea during chemo, my diarrhea and other side effects have been completely manageable on Nerlynx.

    Prior to starting Nerlynx, my tumor markers were rising. Since taking it, they have stabilized. For me, taking it has been the right decision, despite its cost. It is my life we are talking about here.

  • Jessica says:

    Who wrote the article!? They make is sound bad. Touch on the positive aspects instead. They have antidiahreal meds. I’m thankful for this drug & that this multifaceted drug (it has antibacterial, antimalarial, actions that have been lying dormant in our bodies for years that have been overlooked and take on other symptoms, that mask cancers ect. I’m very blessed it has been brought to the market. I’ve been asking for an antimalarial for 5 yrs. it takes cancer to get it, something so simple is made complicated because it needs a trial and studies. lol up The chemical compound for Neratinib & you see it has a quinolone property, also look up quinolone definition, then look up protease inhibitor and anti-malarials. Anti-malarials have protease inhibitors/ block the energy pathway for “supposed cancer”, which is really parasitic pathway being inhibited. Parasitic infections are so overlooked because we are not a third work country which is so wrong. We have various transmissions of a parasitic infection, mosquitoes, cats, dogs, food, unhygienic, raw meat, fish, soil, fruit and vegetables. They hijack our system create a sack like protection amniotic sac, (cancer cell) which acts like a cancer cell protecting it self, it’s resistant to treatments/antibiotics/chemo because it’s a parasitic infection. Similar to the way that you cant use an Anti-fungal as an antibiotic different animal and mechanism. I prayed for this drug Neratinib. Thank you god for listening to my prayers. I found so many articles and did so much research over the 5 years.

  • I have just finished herceptin for her2 positive breast cancer. Mine was early and no nodes were positive so I think I will decide not to take it. My oncologist said the decision was mine. I’ve often had trouble with diarrhea and the side effects of diarrhea don’t sound good


    I’m not going to definatly take this med, it really hurts your liver too, for a 3%? not worth it i’m not gonna be intoxicated

  • Liz says:

    I’m curious how the author feels now that a couple years have passed. I’m on the fence. I’m lobular her2 and ER+. I this far have refused AI and nerlynx. Had enuf. Maybe after I get rid of the emotional spiritual physical and mental bankruptcies I’ll give it a try. Just been too much. I was diagnosed stage 3a lobular Classic.

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