Tag Archives: PF-02341066

Taking the leap into clinical trials

I was initially diagnosed with non small cell lung cancer in April of 2005. My tumor was large (5 centimeters); a poor prognosticator. However, it had not spread beyond my lungs and I was staged at IB. One week after diagnosis I had the lower lobe of my left lung removed. As I was recovering from surgery my new oncologist introduced himself; Dr. Tom Lynch. I had no idea back then, but I was incredibly fortunate to have Tom select me as a patient. The reason behind his coming to me rather than the other way around? As a young (age 45) non smoking woman, I fit the profile of someone who might be EGFR+ and Tom was an early innovator in the investigation and treatment of EGFR+ patients.

I tested negative for an EGFR mutation but in the process acquired arguably one of the best oncologists in the world; someone who was always forward thinking and cutting edge in his approach to treatment. In fact, I was offered a chance to enroll in my first clinical trial soon after surgery. Because of the size of my tumor, adjuvant chemo was indicated and a trial that would include the addition of avastin was proposed. I was having a difficult time even being convinced to have chemotherapy (Tom was adamant) and I couldn’t wrap my head around the possibility of also being a medical research subject. As it turned out I would not have been a good candidate anyway–I am a bit of a bleeder and I was coughing up blood for weeks post lobectomy (there is a small but significant increased risk of serious pulmonary hemorrhage secondary to avastin).

Fast forward to September of 2008, two months after I’d been restaged to IV and advised that I likely only had three to four months to live. At my scan review after two months of tarceva–tried as a last ditch effort even though I was EGFR-, there was nothing but bad news from the radiologist. However Tom shared that a sample of my biopsy had been submitted for further genetic screening and had come back positive for an EML4-ALK translocation (another example of how ahead of the pack he was—the ALK mutation had been identified as a driver in NSCLC only months prior to that).

As we discussed the significance of this finding we also reviewed my options going forward. The way Tom saw it, there were four possible scenarios. I could stay on tarceva, return to traditional chemotherapy, do nothing (that option only underscored how serious my situation was) or attempt to enroll in a phase I clinical trial that targeted ALK mutations such as the one that was driving my cancer.

Would you believe me if I said I never hesitated but instead leapt at the opportunity to be in a clinical trial? Why now but not back in 2005?

This is why.

This image of my scan says it all. The upper lobe of my left lung was now almost completely clouded with consolidated ground glass tumors which had spread to my right upper lobe. And I had been told that I might have three to four months to live two months ago. The math was easy—I had almost run out of time and out of the four options I’d been provided with, only one seemed to offer a glimmer of hope.

And glimmer is the operative word. There was no precedent for me back then—no reason to believe that this trial might actually prove effective. All Tom could offer me was the fact that I had been preceded by one other participant at MGH. ALK+ like me but so debilitated by disease that they were confined to a wheelchair. Their initial response had been extremely encouraging, to the point where the wheelchair was temporarily abandoned. But then they had died, in part due to the toxic effects of the trial drug on their liver.

So this is what I knew. One before me with a promising response who had succumbed both to disease and to the toxic effects of therapy. That the experimental therapy could in fact prove fatal to me as well. But that my cancer would certainly kill me if I did nothing. An easy choice, after all.

And so, on October 1 of 2008 I had my lead in dose of the drug that would eventually be known as Xalkori.

 

Xalkori Launch

We take the stage

Alright Miss Duff. Enough procrastination. Time to write about the Xalkori launch.

From the evening of October 25th through Thursday morning on the 27th, David and I were guests of Pfizer at the Copley Square Marriott in Boston. We were in attendance for the patient portion of the Xalkori launch.

After registering on Tuesday, I located the ballroom where Alice (Dr. Shaw) was scheduled to speak. An interactive display had been installed in the foyer with patient photos and videos, and as I was checking those out I ran into the speaker herself. There was time for a quick hug before she took the stage and I slipped into a seat at the back of the room.

Alice recounted a brief history of the PF-02341066 trial to an audience of about 350 Pfizer employees; the majority of whom were pharmaceutical reps. She was joined onstage by Robert Martensen, an author and physician, who happens to have ALK+ NSLC  and who began taking Xalkori last summer. Of special note, the histology of Dr. Martensen’s lung cancer is squamous, so here is a splendid example of the old exception to the rule theory.

It was interesting to hear the dialogue between two doctors; one of whom was also the patient. At the conclusion of their presentation, we had a ‘practice’ session, and I was able to meet the other ten patients whom I would be joining for our portion of the program the following morning. All of them, (except for myself) were current participants in phases II and III of the crizotinib (Xalkori) trial and had enjoyed positive results that ranged from stable to a whopping 100% response.

On Wednesday morning the eleven of us, plus our caregivers, made a rather dramatic appearance onstage as we lined up behind a white scrim which was then dropped at our feet (the reveal!). After we were individually introduced by the moderators (hello Jonathan and Chris), our families retired to the audience.

It was a moving experience, as each patient took turns describing the impact Xalkori had made on their lives.  I found it rather an amazing vantage point as well; looking out over the sea of faces in the audience, many of whom were wiping away tears.

Each patient was given a chance to answer some prepared questions. When it was my turn, I commented that it wasn’t exactly fair that the moderators were the only ones with teleprompters, given the fact that most of us on stage had done some really hard drugs.  I also asked the audience to take a good look at the eleven hale and hearty individuals (patients) in front of them and to remember that we each had stage IV lung cancer. Given the ravages of the disease as well as the difficult side effects of most traditional treatments, our current state of health was perhaps the most amazing thing of all. Not only had Xalkori given us more time, it was quality time.

After the session concluded, we had the chance to meet some of the people behind the development of crizotinb, including Keith Wilner, Pfizer’s Senior Director of Clinical Research, and then perhaps the biggest rock star of all,  Dr. Jingrong Jean Cui, the scientist who invented crizotinib.

Dr. J. Jean Cui with some of her biggest fans

Jean is the epitome of intelligence, diligence, humility (!) and creativity. She shared with us a tantalizing glimpse of just what lay behind the synthesis of a complex molecule that would become Xalkori.

And this is it: Xalkori

Pfizer thoughtfully arranged a luncheon for the patients and their families, and we were joined by several key members of the team involved in development to market phases of PF-02341066/crizotinib/Xalkori. Possibly not your usual cafeteria chatter.

I had overheard that there would be a tribute to my friend Kevin Brumett, who was one of the very first people in the world to go on what was then know as PF-02341066. Kevin passed away in May of 2009, just a week after marrying his sweetheart, Stephanie Fellingham. With his boundless optimism, energy and generosity, Kevin touched the lives of many. In January of 2009, he had been invited to speak at the Pfizer laboratories in La Jolla, an experience he found profoundly moving. It was only fitting to close the Xalkori launch with a tribute to this exceptionally brave young man who eagerly went down what was then an unproven path.

There was time for a short and much needed break; I felt emotionally tapped out at this point. Then we crowded into buses with the pharmaceutical reps to join in a team building exercise at yet another venue. It was actually a great chance to get to talk to more people, and the product of the exercise was some lovely murals for The Lung Cancer Alliance of Massachusetts.

When finsished, we moved upstairs for dinner, and once again I enjoyed having the chance to converse with members of the crowd. An unsolicited plug for Pfizer here; I was truly impressed by both the sincerity and level of commitment exhibited by their employees. Just a really great group of people.

Just when I thought this day couldn’t be any more meaningful, Dr. Tom Lynch, my original oncologist and now Director of the Yale Cancer Center, walked up to our table. After a few moments to catch up, he took the podium, and knocked the socks off a crowd that on the third and final day of the Xalkori launch, was by all rights exhausted. Tom possesses the uncommon combination of brilliance and a real knack for performance; he is a phenomenal speaker. And his enthusiasm is absolutely infectious. And, of course, I couldn’t help but be pleased that he included the before and after image of my lungs (pre and post crizotinb/Xalkori; nice to see them on the big screen!).

The evening concluded with a moving presentation by Diane Legg and Rich Monopoli, friends and associates of mine as well as co-chairs of the Massachusetts Lung Cancer Alliance. What a day!!

Before I sign off, I would like to say how pleased I was to have people come up and introduce themselves and to say that they read my blog; I am honored. It was also wonderful to be reunited with those I’ve had the pleasure of meeting before; both filming in Meredith and on my trip to the facility in Connecticut. In closing, thank you, Pfizer, for making us feel so welcome and please, keep up all of the good work. You will never know how much it means to our friends, families, and those of us with lung cancer.

Reports from ASCO, 2010

The annual meeting of ASCO (American Society of Clinical Oncologists) is this weekend, and Crizotinib is attracting some attention. Today the plenary session will include accumulated data from the PF-02341066 trial and already there are several online articles in which Crizotinib is discussed.

Medpage has a video interview with the PI (Principal Investigator) of the trial, Dr. Alice Shaw.  She is also my oncologist.

A reporter from Bloomberg Businessweek spoke to me some weeks ago, and today there is an online story about Crizotinib which mentions some of my own experience on trial.

And the Sunday New York Times featured an article in today’s paper that references two promising new cancer therapies; Crizotinib is one of them.

It’s really very exciting to witness and to have been fortunate enough to have participated in what I hope is merely the groundswell of a new era in cancer treatment. That this innovation should also be happening in lung cancer, the cancer that kills more people than all other cancers and which has been notoriously difficult to treat at all but the earliest stages, well, hallelujah.

Next steps

Where to start?  It’s been a busy week.  On Thursday I went to Boston for allergy testing. I sleep on a natural latex mattress and had been using a pillow out of the same material. Several mornings in a row I awakened with a lot of swelling around my eyes and cheeks. After spending the night at a friend’s home and waking up minus the swelling, I returned to my own bed only to have it happen again. I replaced the pillow with one that wasn’t latex and  voila, no more swelling. Because I am in and out of a hospital so much, there was a chance that I had developed an allergy to latex. A prick test (yes, that’s what they call it) came back negative and I am awaiting a blood test, but it seems unlikely that my facial edema was related to latex. A minor medical mystery.

On Saturday, we had a belated birthday party for Peter, who turned thirteen in April. Seven of his buddies spent twenty four hours at our house. The air was thick with adolescent testosterone. When they weren’t eating they were out in the woods using each other as target practice with a battery of air soft guns. They all had on protective gear and were instructed to not shoot each other in the face and/or point blank, and, for the most part, they complied.

The entire air soft concept took me awhile to warm to. Despite my own access to not only cap guns (remember the smell of a freshly detonated cap?) but twenty two rifles as a child, as an adult and a pacifist, I have a general policy against weapons of any sort. Not easily thwarted,  a then-three-year-old August would chew his toast into the shape of a gun. Gradually I acknowledged that an attraction to things that shoot was somewhat intrinsic, and rather than banning firearms, I did my best to stress respect for life while allowing for fantasy play. These new guns do take it to another level. However, the boys had a great time and we all survived.

Sunday afternoon we partook of a more gentile activity, as Peter had a music recital. It was lovely to listen to a wide range of ages and abilities on a variety of instruments, including Peter Duff on guitar.

I turned in early that night, exhausted from the boy party, a big boy party (remember Go Dog Go and “a dog party, a big dog party”; I cut my reading teeth on that book). Yesterday morning I left the house at six a.m. to follow that familiar path down the highway to Boston. All the trees are almost completely leafed out now, and everything is so green. There was also a lot of roadkill. I saw opossum, fisher cat, coyote, deer, as well as some mangled black fur of unknown origin. It is a sad rite of spring;  young animals unaware of the great danger that crossing a highway poses.

At my  appointment, Alice (Dr. Shaw) laid out my treatment options in more detail. My next scan is in three weeks, and will help us to assess how quickly the cancer is developing. At some point I will need to undergo another biopsy, in order to learn more about why I have become resistant to the 1066 as well as to determine what the most appropriate therapy might be. If the pleural effusion has gained in volume, some of the fluid could be removed and analyzed. The presence of the fluid makes it viable to remove ‘live’ cancerous cells that could then be cultured.  Clinically that would be a real advantage, but from a therapeutic perspective a pleural effusion can be difficult to manage, so I am hopeful that such a scenario is not an option.  In lieu of that, I would likely have a wedge resection via VATS, as a punch biopsy would not procure enough material.

As I mentioned before, a HSP-90 inhibitor might be the next logical step.  HSP-90 is an acronym for Heat Shock Protein 90.  In healthy cells, HSP-90 acts in part as a chaperone that shields proteins from destruction. In cancerous cells, a number of proteins can be over expressed and inhibition of HSP-90 may induce apoptosis (cell death) through inhibition of growth signaling pathways. A phase II trial for HSP-90 is now enrolling patients with ALK mutations at MGH.

Alimta remains a fallback possibility and we will be keeping our eyes on a couple of ALK inhibitors in the pipeline (in addition to Ariad, Novartis has one in development).  My fingers are crossed.

In a couple of weeks, ASCO will have it’s annual meeting and this year the PF-02341066 trial results will be presented in a plenary session.  I am interested in seeing the newly published data, including the actual number of participants who, like myself, have relapsed.  I am also happy that the resulting exposure and publicity will make so many more oncologists and patients aware that people with NSCLC should be tested for mutations. It really is the dawning of a new era in cancer treatment.

The (positive) power of the media

L1010275At dusk the past two days, the moon has risen just over the lake, turning the water a shimmery silver.  When I have awakened in the middle of the night , it has been to a world transformed:  moonlight has bleached most everything a bluish white except for what it cannot reach, and that is in deep shadow.

This morning the ground was covered in hoar frost, and the lakes we passed on the way to Pete’s bus stop had the sluggish appearance of mercury.  Frosty vapor rose from the surface; it was simply exquisite.  When I returned home I grabbed my camera and snapped this shot of the leaves rimmed in frost.

Yesterday I drove to Boston for my trial date.  Everything except for the commute is now an abbreviated version of its former self.  My labs and my visit with Dr. Shaw take place in the thoracic oncology wing, and I visit infusion only to be dosed and to pick up a month’s worth of PF-02341066.  All of this is indicative of progress, but it also means less interaction with Marguerite, Sarah and Jose (and no Irene!).  I miss our more extended visits, but each brief reunion feels as if I am greeting dear friends–which is the direction in which these relationships have developed.

Alice still devotes as much time to our appointments as before; she is an extraordinary doctor in this regard.  Yesterday we reviewed the scans I had done almost two weeks hence.  I had been just a wee bit anxious, as it had been necessary to take a four day holiday from the drug, and I had not done that before.  My lungs looked great; everything is stable.  I am hugely relieved.

There is more good news.  ABC was in the house, filming a patient for a report that will air later in the week.  This gentleman had been watching television on June 2nd when the segment on personalized medicine was shown:  he is a young, never-smoker with advanced NSCLC that had not been responding to previous treatments.  Like me, he did not have the EGFR mutation.  When he heard my story and saw the image of my lungs, he was struck by the similarities to his own situation.  Although he lives some distance from Boston, he contacted Dr. Shaw and had his tumor tested for the ALK mutation.  The test was positive, and he started almost immediately on the PF-002341066 trial.  He too has had a fantastic response, and yesterday I had the pleasure of meeting him.  He looks fabulous and he said he feels great as well.

I have also been in close contact with another young, never-smoker who is enrolled in the Korean cohort of the trial.  She also was tested for the ALK-mutation after her sister saw the ABC report and contacted Dr. Shaw.  She too has had a very postive response.

This is all so exciting to me on several levels.  First, any good news from others in this battle is cause for celebration.  Secondly, to actually witness the positive impact of a newscast in which I was a participant.  All too often news is bad news, and we forget that media plays a very important role in the dissemination of information.  And it generally has a ripple effect:  after this new story airs on ABC World News, even more people will become aware of what could potentially be a life-saving treatment for them.

Finally, there is the even bigger picture.  Because I had (and a number of others as well) a positive response to PF-02341066 so early in the trial, there was always the possibility that it was a fluke.  As the trial continues, and a greater number of participants have positive responses, it is looking more like a trend.  I really believe that we are on the leading edge of some big breakthroughs in the study and treatment of lung cancer. November is Lung Cancer Awareness Month, and one of messages that advocates are trying to get across is the need for more funding to be earmarked for lung cancer research.  As one of a growing number of individuals who has personally benefitted from innovative research, I can testify to the validity of this call.  Let’s hope that the individuals and the organizations who can make this happen are listening.

Humble Pie

Yesterday there was an article in the Boston Globe about a young man (high school) who suffered a major spinal cord injury while playing football. He is in rehab learning how to use his upper body again and hoping against hope that he will regain use of his legs as well. His attitude and courage amazed me, and made me feel a bit sheepish about ANY whining I have done about my current convalescence. Piece of cake compared to what this kid is facing and he’s got his whole life ahead of him. That’s the thing: when you start taking yourself too seriously, it is never hard to find another’s situation to put it all in perspective.

On that note, I have returned to household chores such as doing the laundry and cleaning up a bit: last night I cooked dinner and this morning I drove Pete to school. Feels so great to get back into the everyday routines. I also went for a short spin on the exercise bike yesterday. It was kind of trippy, as my ankle has a long way to go before it is flexible, but I’m glad I did it.

The disruption of my regular routines has messed up my sleeping patterns as well. Sleep is one of those things that I am generally very good at; getting somewhat prone and being warm are usually my only two requirements. I am waking up a lot in the middle of the night now and unable to go back to sleep. There are positives to this though. It is a very creative time, as long as I can remember all those great ideas in the morning. And last night I saw a shooting star–a rare treat.

Jemesii helped me tweak my blog a little. I have added the Pfizer video to the mast head, just right of ABOUT, and also provided a link to the ABC interview. Unlike a book, a blog reads sort of backwards, and you have to work a bit to access the early chapters. I wanted the videos to be easy to retrieve as I believe they are both very effective illustrations of the efficacy of the trial. The loose format of a blog is very conducive to the way I work, but ultimately I would like to organize certain “chapters”. For instance, once I have finished recounting the events directly before and after my diagnosis in 2005, I will make it easy for someone to read those in consecutive order. And so on and so on!

In the meantime, I need to mention that several weeks ago I quietly observed a very important anniversary. As of October 1st, it has been one year since I took the lead in dose of PF-02341066. One year of effectiveness and counting. As remarkable as my initial response was, I believe this is even more amazing. In a field in which the extension of a cancer patient’s life by weeks or months is considered beneficial, a year is HUGE. Earlier this year I sent a thank you note to the CEO of Pfizer (to which he graciously responded) and I have just mailed another to him–in recognition of this milestone. I sincerely hope stories such as mine soon will become commonplace, and that cancer really could be a chronic condition rather than a death sentence. Next, perhaps a cure.

And now for a little visual distraction.  These photos are of some antique microscope slides.  I have always loved microscopes, and I found these old slides vastly superior in presentation to the sloppily prepared slides of my youth.  I am attracted to the shapes (got a thing for circles), colors, and all the graphical elements.  And then there is the subject matter.L1010224L1010226.. They are almost like little poems:  Foot of Spider 4, Tongue: Sphinx Moth 3.

The “Now you see it, now you don’t” scan

Before I move on, I thought we’d take one last, long view of the before and after CT scans of my lungs. The scan on top was taken on September 16th of 2008 two weeks prior to starting the PF-02341066 trial. The lower scan was taken seven weeks after my lead-in dose (taken one week before starting regular doses) on November 19th.

beforeandafterlinneacancerslice1beforeandafterlinneacancerslice2 I had been receiving scans every three months for three years at the time of the September 2008 scan.  They had gone from questionable to progressively worse. “Interval increase in size and number of multiple bilateral pulmonary nodules is consistent with progression of metastatic disease”, read a report from August of 2007.

In stark contrast, the radiology report from November 19th of 2008 read: “Marked interval improvement of bilateral pulmonary lesions, with near complete resolution.  Small remaining lesions, left lower lung septal thickening, and left pleural effusion as above.”

I should point out that radiologist’s reports are, by necessity, very conservative in their wording.  Keeping this in mind, “near complete resolution” practically gushed with enthusiasm.

The scan from September illustrates clearly how far the cancer had advanced. The remaining upper lobe of my left lung was literally clouded with malignant nodules.  My right lung also shows a diffuse haziness indicating the spread of disease.  I had once again developed a hacking cough and increasing shortness of breath, and it was no longer possible to engage in many of the activities I had previously.  I was losing ground in my battle with cancer and it seemed inevitable that I would have to concede defeat.

But that was before PF-02341066.  Now I could literally and figuratively breathe again.  I was yet at war, but at long last I had a victory.