[The PointBreak Trial: Boiling results down to four key point]

The PointBreak Trial: Boiling results down to four key points.

September 8th, 2012 - by Dr. Jack West

http://blog.lungevity.org/2012/09/08/pointbreak/

This year at the 2012 Chicago Multidisciplinary Symposium in Thoracic Oncology that’s just ending, one bit of new information was the presentation of the long-awaited PointBreak study. Specifically, the trial pitted Alimta (pemetrexed)-based first line and maintenance chemo against the well-established standard first line and maintenance therapy regimen. It randomized 939 first line advanced non-squamous NSCLC patients either 4 cycles of the “Patel regimen” of carboplatin/Alimta/Avastin (bevacizumab) followed by maintenance Alimta/Avastin (as studied in the early study, led by Dr. Jyoti Patel, that piloted the combination) or 4 cycles of the “Sandler regimen” from the ECOG 4599 trial that established the superior survival for this strategy over chemo alone, of carbo/Taxol (paclitaxel)/Avastin followed by maintenance Avastin.

The primary objective of the trial was to demonstrate significant superiority in terms of overall survival (OS) for the Patel regimen with Alimta compared with the Sandler regimen with Taxol. While the trial failed in that regard, it did provide what I would consider to be four valuable conclusions.

1) Patients did marginally better on the Patel regimen while they were receiving first line therapy. I don’t want to overstate it, because the differences are truly minimal, but as you can see from the curves below, the progression-free survival (PFS) is a little better for the Alimta-based regimen. Admittedly, however, with a median PFS difference of two weeks (6.0 vs. 5.6 months, hazard ratio 0.83) and really no difference in objective response rate (34% vs. 33%), I wouldn’t go so far as to call this a clinically significant difference.

2) Overall survival was completely overlapping between the two regimens. As shown in the figure below, the OS curves for the two arms travel together and just cross over each other multiple times. One may beat the other numerically at a single point in time, but the only trend is that they really travel together.

3) Despite the widely held perspective that the Alimta-based chemo combination is especially well-tolerated, the side effect profiles of the two regimens also didn’t demonstrate a clear winner. In my mind, even without showing a significant survival difference, I would say that the Alimta arm could have demonstrated some superiority for showing equivalent efficacy with notably lower side effects. That didn’t happen. As expected, there was more neuropathy and hair loss with Taxol, but the Alimta arm showed a little more of a drop in blood counts with Alimta. Overall, even the side effect profiles appeared more similar than different and failed to declare a “secondary winner”

4) You can make the argument that the Alimta/Avastin combination was superior to Avastin alone in the maintenance therapy component of the trial. In keeping with the results from the AVAPERL trial that revealed significantly superior PFS (and OS not reported out yet) for maintenance Alimta/Avastin vs. Avastin alone after first line cisplatin/Alimta/Avastin, both PFS and OS are longer (by 1.7 and 2.0 months, respectively) when restricting our review of results only to the 63% of patients who went on to maintenance therapy (the others dropping off because of progression, prohibitive side effects, or other complications), as shown in the figures below. This was a pre-specified question that the investigators wanted to address, though it wasn’t the main question of the trial. In real life, when we’re making recommendations about what treatment to start with, we can’t know which patients will do well through first line chemo and which ones won’t.

Despite the difference in efficacy of maintenance therapy, at the end of the day, there wasn’t a significant difference in overall survival when you add in the patients who dropped off before maintenance. And then, there is an equalizing effect from post-trial subsequent therapies, though less than 2/3 of patients received further therapy, when these are patients we’d have really generally hoped and expected should have received further treatment (in trial after trial, we consistently see fewer patients received with second line and later systemic therapy than oncologists believe they’re treating). Patients assigned to the Alimta arm were significantly more likely to get Taxotere (docetaxel) afterward, and patients assigned to the Taxol arm were significantly more likely to get Alimta afterward (as you’d expect).

So what does it all mean, at the end of the day? Over the past few years, many lung cancer experts (including this one) have tended to favor carbo/Alimta/Avastin over the established ECOG 4599 trial regimen because we felt it was extremely likely to be at least as good if not significantly better than the carbo/Taxol/Avastin regimen. Indeed, it was just as good, but the PointBreak trial disabuses us of the notion that it might be significantly better, even with the advantage of giving what truly appears to be a more effective maintenance therapy with the Alimta/Avastin combination. At the same time, many of us who treat lung cancer patients every time might have estimated that there would be significant advantage in terms of side effects for the Alimta regimen compared with the Taxol regimen. The actual evidence doesn’t support that conclusion either.

With the dust settling now, I’d say that the PointBreak trial leaves us with the idea that it’s appropriate to continue to do exactly what you’ve been inclined to do. Some people will value the Alimta regimen because of the much lower risk of neuropathy and hair loss, while others will favor Taxol as being well established, considerably less expensive, and achieving results completely comparable to the carbo/Alimta/Avastin regimen overall. You can make a good argument that for patients who get as far as the maintenance portion, patients are better served by the Alimta/Avastin combination than Avastin alone, and that remains my preference, though we can also look forward to getting a more direct test of maintenance therapy strategies from the ongoing important ECOG 5508 trial.

I think a leading question now is whether insurers will use the results to justify refusing to pay for the more expensive Patel regimen when the evidence indicates that patients can experience the same survival with the less expensive Sandler regimen. We’ll have to see how our pre-authorizations change in the next few months.

Do these results lead you to feel comfortable with either regimen, or do you clearly favor one? If you had to pay more to receive the Alimta-based regimen, would you accept a significant co-payment to cover the difference?

[Celebrating 6 Years of LIFE]

Celebrating 6 Years of LIFE

September 7th, 2012 - by admin

by Lois Green

http://blog.lungevity.org/2012/09/07/ce ... s-of-life/

I am a runner and I diagnosed with lung cancer in 2006.

I didn’t have any risk factors. I was relatively young and healthy and by sheer luck at a company health fair I was encouraged to see a specialist for my asthma. The rest is history.

The year that followed my lung surgery was EPIC!!! The support from my friends, family and colleagues was OVER THE TOP! The letters I received are treasures etched in my heart forever. I ran my next marathon 9 months after surgery with my daughter Tara at my side through every mile. We raised $20,000 for LLS. That was incredible!

But not everyone is as lucky as I was to have found their lung cancer in its earliest stage, or have the support from friends and family during their cancer experience.

Lung cancer impacts one in 14 Americans and kills more than breast, prostate, colorectal and pancreatic cancers combined.

Currently, only 16% of people diagnosed with lung cancer survive 5 years post-diagnosis, a percentage significantly lower than that for each of these other cancers.

While colon, breast, and prostate cancer all have reliable early detection tests, lung cancer does not.

About 55% of all new lung cancer diagnoses are among people who have never smoked. I was one of them.

Lung cancer claims approximately 160,000 lives per year.

Less than $2,000 of Federal research dollars are spent for every lung cancer death, compared with $25,000 for breast cancer and $12,000 for prostate cancer.

The media focuses on a variety of cancers, but often overlook lung cancer because of the stigma associated with the disease. Many people think that smokers should know better and expect related health problems when they smoke. As a nation we don’t give enough attention to lung cancer treatment and prevention.

And the public should know that never smokers get lung cancer too. Anyone with lungs can get it, like me.

Earlier this year I attended a friends dinner party where I was among several doctors and their spouses. We had finished dinner so I excused myself from the table to indulge in the variety of desserts only to discover on my return that I was the topic of conversation for being a lung cancer survivor and a runner. The doctor sitting next to me turned and said “You’re a lung cancer survivor? That is amazing because when most people are diagnosed with lung cancer it is already too late.” That moment raises an emotion in me, and I am reminded of how lucky I am.

On May 4, 2012, I attended the annual HOPE Summit for LUNGevity in Washington D.C. On arrival we meet with everyone we bonded with from last year and it is more exciting when we learned the attending lung cancer survivors has tripled in attendance this year! The HOPE Summit Agenda is always packed with fascinating people and events. The second morning of the summit I entered the conference room and “HOPEtastic” was everywhere. Survivors who have written books had brought copies to share. Keynote speakers shared their incredible stories, research doctors educated us on many topics, and media were there to video personal testimonies.

Randall Broad, Author and stage III lung cancer survivor reminded us all that “It’s An Extraordinary Life..Don’t Miss It”. There wasn’t a dry eye in the room when Randy told his story.

Jorge Gonzalez was 47 when he was diagnosed with stage III lung cancer on May 28, 2011. He was young, relatively healthy and a non smoker without risk factors. He is married with two daughters and treasures the time with his family. Jorge says, “The biggest fear I had when I was diagnosed was over my family. I didn’t know what to do so I made arrangements, I wanted to make sure things were taken care of incase I didn’t survive this.” But he did. “Everyday above ground is a good day.”

Then there was Sara Ratzenberger, who arrived in a wheel chair with an iv and nasal cannula for added oxygen. Nothing was going to stop this brave little girl, young lady, from attending the HOPE Summit. Sara came with every ounce of determination. She is stage 4, 1.5 year Survivor. When I see Sara on Facebook, she is pure Sunshine and lives every day to the fullest. Sara is pretty with blonde hair, blue hair (for LUNGevity) or sometimes very little hair. We all love Sara. When I am less motivated to run, I peek in on Sara and I have sudden purpose. Sara recently had a second thoracotomy.

I recall the tender moment after my surgery, when I could barely open my eyes. My Dad, (who was a smoker) came in my room alone and placed his hand on mine over the iv and said “I hope I didn’t do this to you”. “No Dad, you didn’t.”

People!! This is NOT a smoker’s disease. Lung cancer does not discriminate.

I cannot fathom a second thoracotomy. I had a pity party when my ICU nurse assisted me out of bed for my first walk on the metal walker. With lines/tubes extended from neck, my arm, my waste, and my back, I sobbed in those first steps until my nurse *Mary* said “Lois, you will run again”.

When HOPE Summit concluded our cup runneth over with friendship, renewed spirit and Hope.

I didn’t write a book. I wasn’t a keynote speaker. I didn’t arrive in a wheel chair. I never had chemotherapy or radiation. My dear friend who I worked with in the East Greenbush plant is going through chemo right now. I asked him to describe chemo to me. The list was long and he concluded with “Lois, I’m going to be a survivor like you.”

Our survival inspires others and gives other’s Hope too!

On November 4, 2012, I am running the New York City Marathon with my daughter Tara and my dear friend Jenny Lee. We are representing The LUNGevity Foundation.

LUNGevity is the largest lung cancer nonprofit funding research into early detection and effective treatments of the disease. Our fundraising commitment is $8,000. The President of LUNGevity, Andrea Ferris, personally invited me to their first entry in the NYC marathon.

Our mission is to raise awareness that LUNG CANCER IS THE NO. 1 CANCER KILLER and if it can happen to me, it can happen to anyone.

I’m not a loyal sports fan. I have my favorite teams, but when the event is near I always find myself routing for the under dog. This is how I feel about LUNGevity. I have been given the platform to raise the awareness NOW.. LUNGevity’s mission is to improve survival rates and promising research for early detection. That will save lives!

Will you join me in the fight against lung cancer? Every step is a step closer to a cure.

I believe in you…Thank you to my friends, family and supporters (and LUNGevity!) for believing in me.

Lung cancer didn’t just happen to me. I believe it happened for me -so that maybe I can make a difference against this disease and for others.

With LUNGevity, I have HOPE.

August 31, 2012, I celebrated LIFE and 6 years of being lung cancer free!

Please celebrate with me by showing your support of lung cancer research.

Please donate

http://events.lungevity.org/goto/teamgreen