Thinking about a “drug vacation” from crizotinib? Read this first!

Original post is on The ROS1ders website

I’m Janet Freeman-Daily, a cofounder of The ROS1ders.  I’m writing this post in response to some of the comments we’ve seen recently in our private Facebook group “ROS1 Positive (ROS1+) Cancer.”

Many of our members who have ROS1+ cancers take the targeted therapy crizotinib (Xalkori), a tyrosine kinase inhibitor (TKI).  It was approved by the US FDA for ALK+ non-small cell lung cancer (NSCLC) in 2011, and for ROS1+ NSCLC in 2016.

Many ALK+ and ROS1+ NSCLC patients have had long-term stability or no evidence of disease (NED) on crizotinib, and are tolerating it well. Some of these patients suggested they might “take a vacation” from crizotinib for a while, as some people do with chemo. They think this could help them avoid developing resistance to crizotinib (which could allow them to stay on the drug longer), and that they can start taking the drug again later if the cancer returns. Their oncologist might even agree with this idea.  But …

PLEASE — If crizotinib (Xalkori) is working for you and you can tolerate it, consult a ROS1 expert before stopping treatment!  

If your doctor tells you should stop taking crizotinib for a medical reason (like a severe side effect or toxicity), or temporarily during surgery or radiation, you should follow their advice. But don’t stop taking crizotinib just because you want a drug vacation.

ROS1+ cancer is a rare disease. Oncologists who have seen no or few ROS1 patients usually haven’t followed the fast-moving research into this disease.

Dr. Ross Camidge and Dr Robert Doebeleare among a handful of doctors who have treated dozens of ROS1+ and ALK+ patients with crizotinib. Globally, they are considered experts in ROS1+ NSCLC.  Both have told me they think it’s a bad idea for patients to stop taking Xalkori just because they’re NED or stable on the drug. Below are the reasons they gave me.

  • Targeted therapies are not the same as chemo. TKIs inhibit the cancer, but do not kill it. For metastatic cancer patients, cancer cells likely remain in the blood, lymphatic system, or body (we just don’t have the means to detect them–that’s why we say “no evidence of disease” instead of “cancer free”).  If you stop treatment, you stop inhibiting those cancer cells, and any cancer that remains can resume growing—sometimes very fast. Those cells can continue to mutate. There is no guarantee that crizotinib will be effective against your cancer when you restart it after a “drug vacation.”
  • TKI flare is well documented for EGFR and ALK patients on TKIs like Xalkori.  What is TKI flare? Some patients (not all) on TKIs who stop taking the drug can see their cancer grow quickly after just a week or two. When they restart the drug, it doesn’t always work again.
  • We don’t have much evidence of what may happen if NED patients stop taking their TKI, except for one study.  In the study,  EGFR+ NSCLC patients who had no evidence of disease on Tarceva (a TKI like Xalkori) stopped taking their cancer drug. All saw their cancer return within a year.
  • While chronic myeloid leukemia (CML) patients on a TKI (Gleevec) have been able to stop taking their TKI, their blood cancer is not as aggressive and deadly as lung cancer.

Each patient has the right to make up their own mind about their treatment,  In my case, I have had no evidence of disease on crizotinib for 6 years. When I asked about stopping crizotinib, Dr. Camidge has told me that he does not want me to stop taking my cancer drug. I’m going with his expert opinion.

Crizotinib (Xalkori) approved for ROS1-positive NSCLC!

The anticancer pill I take in my clinical trial, Xalkori (generic name crizotinib), was approved today by the FDA for my type of lung cancer: ROS1-positive non-small cell lung cancer.  I’m one of the 50 patients whose results were included in the clinical trial data.

In addition to being happy that I found an effective treatment for my lung cancer–I’ve had No Evidence of Disease for 36 months and counting–I feel proud to be part of the research that is making new cancer treatments available for more patients.

Precision medicine, targeted therapies, and clinical trials are awesome.

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Edit 2016-03-11 2 PM to add:

Some people have asked what this approval means to my participation in the clinical trial.

The short answer:
Nothing has changed for me. I’m still in the clinical trial, and I still get my drug free (but have to pay for my travel).

The long answer:

Last April, Xalkori for ROS1+ NSCLC received “breakthrough” FDA designation, which is one type of accelerated FDA approval. The accelerated approval process allows the FDA to grant approval before a Phase 3 clinical trial is completed, but still requires a Phase 3 trial to be completed eventually. So my clinical trial must continue until the Phase 3 trial is complete, or the FDA will pull its approval of Xalkori for ROS1 NSCLC.

Xalkori originally received breakthrough designation for ALK+ NSCLC, and was granted FDA approval through the accelerated process in August 2011 (the fastest drug approval to date). The Xalkori for ALK+ NSCLC phase 3 clinical trial still continues over four years later. So I suspect my clinical trial will be continuing for some time.

However, even if I left the clinical trial, Xalkori is already covered by most insurance plans, and today’s FDA approval means pretty much all plans will cover it. However, the copays vary considerably.  Some plans cover it as a pharmacy benefit with a substantial out of pocket expense.  Others cover it as a medical expense, with a standard deductible.  I haven’t checked to see how (or if) my plan covers it.

I plan to stay in the clinical trial at the University of Colorado for the forseeable future.  I like having regular access to some of the top experts in the world on ROS1 cancer and molecular testing for precision medicine.  My writing income goes to fund their Lung Cancer Colorado Fund for lung cancer research.  I also participate in their research as a patient advocate on the NCI-sponsored CU lung cancer SPORE (Specialized Program for Research Excellence) and get to learn about cutting-edge cancer research, which satisfies the geek in me. Besides, I’ve grown fond of several people I’ve come to know at CU.  It’s become a second home of sorts.

So, yeah, this approval does not change my treatment. But hopefully it will make the treatment more available to more patients ASAP.

My drug is a breakthrough!

Woohoo!  My clinical trial drug may get FDA approval soon!   It’s about time.

The clinical trial in which I participate has been running for over three years.  I take Xalkori (crizotinib) for my ROS1-positive non-small cell lung cancer.  Early phase clinical trial results  announced last year show around 72% of patients experienced measurable shrinkage of their tumors, and another 12% achieved stability.  This is remarkable, considering most chemos have a response rate around 20%.

The average crizotinib response lasted about 17 months, with half of the patients still responding when the data was collected for the journal article.  I personally know at least four people (including me) who responses have lasted over two years (two of them are not on the trial).

Today Pfizer announced it had received US FDA “breakthrough” designation for Xalkori treatment of ROS1+ non-small cell lung cancer.  This means it is on the fast track for FDA approval for treatment of ROS1 NSCLC (after already being approved for treatment of a different lung cancer mutation).

My marvelous clinical trial drug may finally get FDA approval.   It’s sort of moot, in a way, because the evidence of its effectiveness is so outstanding that most US insurance companies are already paying for crizotinib treatment of ROS1 NSCLC.  But it is still cool.

Pfizer Receives U.S. FDA Breakthrough Therapy Designation For XALKORI® (crizotinib) For The Treatment Of Patients With ROS1-Positive Non-Small Cell Lung Cancer

Coincidentally, I have my clinical trial appointment today, and I’ll be talking with one of the lead investigators (my oncologist, Dr. Ross Camidge) about what this announcement means for those of us still on the trial.

Clinical Trial Check-In Number 18

Denver gifted me with a warm, bright day today — clear skies, 60 degrees, a hint of breeze — perfect for sitting on a sun-drenched bench and basking in the glow of another clean scan. I’m still No Evidence of Disease (NED) status. Woohoo!

You’d think I would have had enough radiation for one week, but that spring sunshine was simply irresistible after such a long winter.

I had a PET-CT scan as well as a brain MRI and lab work yesterday, and had my once-every-eight-weeks visit with my clinical trial oncologist Dr. Camidge at University of Colorado this afternoon. Today I started cycle 19 on the drug Xalkori. Each cycle is 4 weeks, so I’ve been on this drug trial for 76 weeks now, which is almost 17 months.

I’ve been NED for nearly 15 months on Xalkori. According to interim results published about this clinical trial last year, only myself and one other person achieved NED on this trial. It’s possible I don’t have many cancer cells available to mutate and develop resistance to the drug. My particular flavor of lung cancer (ROS1-driven NSCLC) hasn’t been studied very long — the first article about it was published in January 2012 — so little data exists to know what will happen in my case. Xalkori may continue to suppress my cancer for years. It’s cool to hear my doctors say they have no idea of how long I might have left, and know they’re being honest with me. I’m an outlier for those gloomy stage IV lung cancer statistics.

I feel so fortunate to be blessed with more time to enjoy family and the miracle of life. I aim to make good use of it.

Speaking of making good use of my time … should I mention I have to work on tax returns after I fly home? Nah.

The Side-Effects Samba

Treating side effects of cancer treatment is at times an intricate dance.

Aggressive, long-term cancer treatment can leave one with lingering side effects. Two side effects I live with are peripheral neuropathy and hot flashes. Both are pesky during the day, but are even more bothersome if they decide to flare up during the night and rob me of sleep. When I don’t get a solid eight hours of sleep, my chemobrain (another pesky side effect) gets noticeably worse.

When I started cancer treatment, I took Ambien to help me sleep — without it, I was awake many hours each night. But Ambien suddenly stopped working for me about a year after I started using it. After a relatively sleepless month, my oncologist recommended I take gabapentin about an hour before bedtime to reduce nerve pain from neuropathy, calm my hot flashes, and make me sleepy. I took 300 mg of gabapentin at bedtime and slept well most nights, even though the drug left me groggy for a few hours every morning.

A couple of weeks after starting gabapentin, I started taking Xalkori as part of a clinical trial. A known side effect of Xalkori is edema. If edema occurs with Xalkori, it usually isn’t severe until the patient has been on the drug for several months. Lucky me — my legs blew up like balloons after just a few weeks. The edema and resulting joint pain were severe enough that I asked my trial oncologist about reducing my Xalkori dose. After weighing my options, I decided to stay on the full dose of Xalkori in hopes it would maintain my No Evidence of Disease status longer. I managed the edema somewhat with compression hose, a diuretic, and exercise.

My mental fuzziness seemed to increase gradually over the months, so I had another discussion with the oncologist about managing side effects. I decided to try melatonin at night to help me sleep, and reduce the gabapentin to 100 mg at bedtime. My sleep was unaffected, and I seemed a bit more alert in the morning, although the neuropathy in my feet started to increase.

About a month after this meds change, my edema decreased. I asked my oncologist if the reduced edema might be related to lowering my gabapentin dose, and he said yes. This was the first time I’d heard that gabapentin might cause edema. I reread the gabapentin drug insert, and there it was in the common side effects: “swelling in your hands or feet.”

So, if I completely eliminate the gabapentin, my mental clarity might increase and the edema might lessen or even disappear, but the neuropathy (which was beginning to interfere with my walking) and the sleep problems might increase. Do I dance left, or do I dance right?

Two weeks ago, I chose to stop taking gabapentin. As I’d hoped, the edema has gone down; it’s not completely gone, but I can skip the compression hose and diuretics some days without my legs becoming uncomfortably puffy by evening, and the joint pain has eased. Surprisingly, my neuropathic foot pain is a bit better. However, the nighttime hot flashes came back with a vengeance, and I haven’t had a good night’s sleep since. Ironically, the lack of quality sleep makes me even more groggy during the day.

It’s all a dance. Now if someone could just tell me what step comes next ….

Sunny with a Tinge of Dark

This morning, after I checked a few posts and messages in an online cancer forum, hubby Gerry and I made a Costco run.  Our conversation en route was pleasant enough, but I found myself feeling increasingly grouchy.  Today was a crispy, brilliantly sunny day in Western Washington. Why was I leaning towards dark?

When I started talking to Gerry about conversations on the cancer forum, I realized why. A friend in my ROS1 lung cancer trial who has been on Xalkori for a year longer than me and whose cancer is slower growing than mine, told me his last scan showed a possible progression.

He was calm and composed about this.  Both he and I had been told the effectiveness of Xalkori against our ROS1 cancers won’t last forever, that we’ll eventually develop resistance to the drug.  We both were given contingency plans for treatment once progression showed up.  This wasn’t an earth-shaking, end-of-life event.

But yet, it was a noteworthy event for me.  Those hypothetical discussions had just become real.

I’ve had clean scans for ten months.  I usually feel good (I’m used to overlooking both the temporary and permanent side effects of treatment). I’m exercising and gradually regaining some of the muscle mass I lost in cancer treatment.  I’m writing again.  I’m going out with friends.  I’m even planning some vacation travel for next year.  Most days, I don’t think of myself as a cancer patient.  I can sometimes even blog about my cancer without the gut-wrenching realization “I have CANCER” sneaking into my awareness.  Life is … NORMAL (for unusual definitions of “normal”).

But normal will not last. Cancer survivor reality raised its ugly head. Someone among the thirty-some members of my ROS1 clinical trial — someone I know personally — probably has progressed.  We ROS1ers are NOT invincible.  Xalkori will NOT last forever.  This time next year, I might be dealing once again with radiation, chemo, or a new trial drug. My grouchiness was similar to that caused by scanxiety: I had to face the reality that my cancer will likely come back.

Once I identified the source of my fears, the momentary darkness passed, and life went on.

We bought a nice bottle of Bailey’s Irish Cream at Costco.

Why I’m in a Clinical Trial

The fact that I’m alive is a modern-day medical miracle. And I owe it to clinical trials.

In early 2011, I was in good physical shape, slightly overweight, eating healthy and exercising regularly. After I tolerated a nagging, slight cough for a few months without any relief from antibiotics, my doctor ordered a chest x-ray. Before I’d left the lab, she ordered a CT scan. Before I arrived home from the clinic, she called: the radiologist saw a mass in my lung. Two days later, a Friday, I saw a pulmonologist who performed a biopsy. He called me Tuesday evening, May 10, 2011, with the news: at age 55, as a never smoker, I had lung cancer.

Scans and tests over two weeks rendered a diagnosis of stage IIIA non-small-cell adenocarcinoma complicated by obstructive pneumonia. I was not a candidate for surgery, but the oncologist considered me curable. My tumor didn’t have either the EGFR or ALK mutations.  After ten days in the hospital and weeks of IV antibiotics, I recovered enough to get radiation therapy and low-dose chemotherapy, followed by one full dose of chemo (my side effects were too severe to allow me to have more chemo). I finished first-line treatment in early August 2011.

My post-treatment CT scan in late September 2011 showed the lymph nodes were almost completely clean, and the tumor had shrunk by over 90%. I thought I had a great chance at a cure. In the next two weeks, I underwent several tests to determine if I was healthy enough to have the lung removed. One of the tests was a PET scan, which found a hot spot on my right front collarbone. A few days, later two lymph nodes were removed in an open biopsy and found to be more of the same cancer. I was now stage IV–metastatic lung cancer. No lung surgery for me. The radiation oncologist advised waiting rather than radiating because I’d had a large volume of lung zapped already.  My oncologist also advised waiting a few months before starting a new chemo to give my body time to recover.

I decided to learn more about treatment options during those few months. From my participation in the Inspire.com Lung Cancer Support Community, I’d learned about the Lung Cancer Mutation Consortium Protocol clinical trial, which tested for ten mutations in lung cancer tumors. I had lots of slides courtesy of my two new tumors; testing for more mutations sounded hopeful, and I liked the idea of contributing in some small way to the science looking for a lung cancer cure. I searched for the trial on clinicaltrials.gov and emailed its contact person at the University of Colorado in Denver. I couldn’t travel to Denver (my pulmonologist thought my hollow tumor might cause a collapsed lung if I flew), but UC accepted me into the trial and tested my tissue anyway.  A few weeks later I received a call from the head of the trial, Dr. Paul Bunn: I had none of the ten mutations.

In two months, a visible 3-inch tumor grew by my right collarbone in the area where the lymph nodes had been removed. I had a CT scan the day after Christmas, met with my oncologist to discuss treatment, and had a power port installed. After six rounds of chemo over five months, CT and brain MRI scans showed all my original tumors were gone, no new tumors had appeared, and the collarbone tumor had shrunk over 90%. We decided to go for a possible cure with more radiation.  Six weeks later, my Sep 2012 PET-CT scan showed the original tumors were gone and the collarbone tumor was dead. However, I had two new nodules suspicious for cancer, this time in my right lung. Twice now I’d recurred within two months after finishing treatment. What to do next?

Someone on the Inspire.com forum suggested that because I was a young, healthy, never smoker with adenocarcinoma, I fit the profile of patients who had new mutation called ROS1. The poster was in a ROS1 clinical trial in Boston, but the trial was also at University of Colorado. I asked my oncologist about ROS1 testing, but he hadn’t heard of it (the research had been published just nine months earlier). While visiting family in Denver, I arranged to meet with Dr. Bunn and learned UC now tested for new mutations, including ROS1 and RET, and that my tumor had a 10-20% chance of having one of them.  I agreed to let UC test my remaining slides.

I had a biopsy a week later. The pulmonologist said he got a good sampling of the larger nodule but couldn’t find any cancer cells. We decided to wait a month and do another CT scan to see if either nodule grew. The very next day, an email from Dr. Bunn told me I tested positive for ROS1. UC had an opening in a clinical trial that involved a pill called Xalkori, which targeted cells having the ROS1 mutation.  Since I didn’t have a biopsy confirming cancer, Dr. Bunn offered to hold a trial slot for me pending results of my next scan.

My October 2012 chest CT showed the smaller nodule grew nearly 50% in one month. I called UC the next morning and started the process to apply for the ROS1 clinical trial. They agreed to consider me without a biopsy. I scrambled to collect all my medical files and scan CDs. Five days later I flew to Denver for two weeks, hoping I’d pass the screening and be accepted into the trial. I took my first Xalkori pill November 5, 2012.

For the next sixty days, I flew to Denver every two weeks, departing Seattle on Monday and returning home Wednesday. I had blood and urine tests every visit, along with other tests (like EKGs and eye exams), and a clinic visit at whichI met with the doctor to review test results and discuss symptoms. I then flew home with two weeks worth of pills. The first PET-CT scan on New Years Eve showed my two lung nodules were gone and no new hot spots—my first clean scan in 20 months of lung cancer. The side effects I experienced were far easier than either chemo had been. I had my life back.

After the first scan, my visits to UC shifted to every four weeks; after ten drug cycles, they shifted to every eight weeks. Now at UC visits I have blood work, a PET-CT scan, a visit with my UC oncologist Dr. Ross Camidge, and a brain MRI every six months. I have blood work done at my home clinic in off months.

I am not cured–the Xalkori only suppresses my cancer. However, Dr. Camidge has a plan for treating my recurrences.  It’s an odd existence, living from scan to scan. I’ll be in treatment for the rest of my days. Yet I’m hopeful that if/when each clinical trial stops working, a better one will be waiting for me.  Maybe they’ll find a cure for me before I die.

And in the meantime, I’m living.