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Mantras of the Cancer Revolution

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Here’s an inspiring and hopeful talk about finding cancer treatments.

Targeted therapies are revolutionizing the way cancer is treated. One of the leaders of this revolution is Dr. Ross Camidge, Director, Thoracic Oncology Clinical Program at University of Colorado Hospital. He recently gave a talk to Colorado State University’s biotech students, using examples of his lung cancer research to inspire the students to careers in biomedical science.

CSU Career Center’s BioTech Connect: Ross Camidge

RECAP — Mantras of the Cancer Revolution:

The revolution in cancer treatment happened when the effectiveness of crizotinib for ALK+ lung cancer was discovered. “The whole drug development industry in cancer changed overnight. It wasn’t about finding one drug that was going to work a little bit in everybody. It was about findiing a drug that worked amazingly well in a small number of people.”

Camidge stated the following “mantras of the cancer revolution”:

1. One size does not fit all
(personalize cancer treatment based on each individual’s cancer)

2. Don’t walk away from a good thing
(if the targeted drug is working, stay on it as long as possible)

3. If the cancer moves, follow it
(if the cancer moves into brain, make a drug to treat the brain)

4. Question everything

Disclosure: Dr. Camidge is my clinical trial oncologist. I feel incredibly blessed to have him leading my lung cancer team.

What Is an “Off Label” Cancer Drug?

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Sometimes the term “off label” comes up in discussions of cancer drugs.  What does “off label” mean?

All prescription drugs sold in the USA have been approved for use by the U.S. Food and Drug Administration (FDA).  After a drug is approved by the FDA, it sometimes is used for different purposes or in different populations.  That is “off label” use of a drug.  As WebMD explains, it’s perfectly legal. Per the National Cancer Institute’s definition, off label is “the legal use of a prescription drug to treat a disease or condition for which the drug has not been approved by the U.S. Food and Drug Administration.”

Consumer Reports states off label drug prescription is actually very common.  More than one in five outpatient prescriptions today are written off label.  For instance, Neurontin (also known as gabapentin) was originally approved to treat seizures.  It is now also used to treat nerve pain and neuropathy – an off label use.  However, one trusts that one’s doctor will only prescribe a drug with good evidence that drug is useful for the patient’s disease or condition.

Two types of off label use occur. The first type is when a drug is used to treat the approved disease, but used in a manner different than stated in the FDA approval.  For instance, use of the antidepressant Zoloft is off label in children (Zoloft is FDA approved for adults only); taking a drug in a larger dose or on a different schedule than that approved by the FDA is also off label. The second type of off label use is when a drug is used to treat a condition or disease different than that for which the drug was originally approved.

Cancer drugs are sometimes used off label to treat metastatic patients who have exhausted traditional treatment options, but only if evidence indicates the drug might be effective against the patient’s particular cancer situation.  For example, crizotinib (Xalkori) was approved by the FDA only for non small cell lung cancer (NSCLC) patients whose tumors tested positive for the ALK translocation (a type of mutation in a specific gene called ALK).  In addition, the approval stated the patient’s ALK-positive (ALK+) status had to be determined by a specific molecular test.  Prescribing Xalkori for patients who test ALK+ using a different type of test (genomic profiling) is an off label use, because the patients weren’t tested with the specific test named in the FDA approval.  This is not a big deal, because research indicates both tests identify ALK+ tissue with high accuracy.

Xalkori is also legally prescribed for a different disease: ROS1+ lung cancer in patients (like me). ROS1 is a different tumor mutation than ALK, but has a similar structure–technically, ROS1+ NSCLC is a different disease than ALK+ NSCLC. This is an off-label use, because Xalkori has not been approved for treating ROS1+ lung cancer.  Xalkori for ROS1+ lung cancer has been in clinical trials for over two years, with a goal of someday obtaining FDA approval (this is the clinical trial in which I am enrolled). Strong evidence from this clinical trial indicates Xalkori has a high response rate in ROS1+ lung cancer patients, so oncologists are now prescribing Xalkori for this use even though it’s not approved by the FDA for that purpose.

Even a drug that’s approved to treat a particular cancer can be used to treat that cancer in off-label ways. Examples are when a drug normally approved for first line treatment is used for maintenance, or when the dosing interval differs from the schedule called out in the FDA approval.  A friend who has metastatic lung cancer could not tolerate the standard combination chemotherapy for lung cancer because he couldn’t have a platinum drug.  He wanted to have Gemzar, a relatively well-tolerated chemo, off label as a single agent (Gemzar’s FDA approval says it must be used with a platinum drug). After consulting several different oncologists, all of whom wanted to put him on hospice, he found an oncologist willing to give him Gemzar off label as a single agent.  My friend was stable on Gemzar for over two years.

As genomic testing identifies more mutations in different types of cancer tumors, drugs that are FDA approved for one type of cancer – say, a BRAF inhibitor for melanoma– might be tried in a BRAF+ lung cancer patient.  Or, an oncologist might prescribe a cancer drug off label after a functional profiling assay indicates a drug approved for a different cancer is effective against a patient’s tumor tissue. Until FDA approval is given for the drug to be used in a different cancer, this is considered an off label use. However, it could also be a life-saving use for the patient.

“As a cancer patient, it’s always a good idea to ask your oncologist what evidence he has for using a drug off label to treat your cancer. Most oncologists will cite results from early research or a clinical trial. If they don’t have such evidence, ask LOTS of questions. You as the patient are ultimately the one assuming the risk of an off label drug.”

Assuming one has an up-to-date and responsible oncologist, a cancer patient’s primary concerns regarding an off label cancer drug are usually side effects, and whether their insurance will cover a non-approved use of that drug. Sometimes insurance companies will not cover a pricey drug used off label.  When oncologists started prescribing Xalkori for ROS1+ lung cancer outside of clinical trials, some insurance companies refused to cover the expensive drug (around US $10,000 per month) because it was not FDA approved for that type of cancer.  However, I’m hearing more ROS1+ LC patients say their insurance is covering Xalkori even without FDA approval. Insurance companies are learning to adapt to the changing molecular landscape of cancer, just as researchers, oncologists, regulators and professional organizations are.

The times they are a changin’.  Off label cancer drugs may be the new black.

Lung Cancer’s Highlights from 2013 and Predictions, Hopes for 2014 – The First LCSM Tweetchat of 2014

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This is a reblog from the #LCSM Chat blog (posted with permission). I changed the post to include links to the blog sites where comments about the chat should be posted.
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Lung Cancer’s Highlights from 2013 and Predictions, Hopes for 2014 – The First LCSM Tweetchat of 2014

By Dr. H. Jack West 

The end of a year is always a time for reflection on the past alongside hope for the future, so our upcoming lung cancer social media tweet chat on twitter (#LCSM on twitter) will focus on everyone’s thoughts of the most significant developments in lung cancer over the past year, along with predictions and hopes for the coming year.

Please join us Thursday, January 2nd at 8 PM Eastern, 5 PM Pacific on Twitter, using the hashtag #LCSM to follow and add to our one-hour chat with the global lung cancer community, where we’ll cover the following three questions:

1) What do you think were the biggest advances in lung cancer in 2013?

2) What do you predict as key changes in lung cancer in the upcoming year?

3) What is your leading possible hope/goal for the lung cancer world in 2014?

It should be a lively, upbeat discussion, so please join us Thursday, or share your thoughts on the #LCSM Chat blog or on Cancergrace.org before or after the live event. Hope to see you there!

December 19 #LCSM Chat: “Lung Cancer Screening – The Good, The Bad and the Indolent”

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[This is a reblog of a post on the #LCSM Chat website, shared with permission (it’s really easy to give myself permission to reblog something I wrote).]

The next #LCSM Chat will occur on December 19 at 5 PM Pacific Time (8 PM ET), and will be moderated by Janet Freeman-Daily. The theme will be “Lung Cancer Screening – The Good, The Bad and the Indolent.”

Discussion topics for #LCSM Chat:

T1: For patients who don’t fit “older heavy smoker” profile, should doctor order low-dose CT screening if patient requests it? #LCSM

T2: Some lung nodules are not cancer. When are you comfortable just watching a lung nodule instead of treating it? #LCSM

T3: A new blood test detects w/ 90% accuracy if lung nodule IS NOT cancer (but can’t tell for sure if it IS). Is this useful when combined with low-dose CT screening? #LCSM

Background

The National Lung Screening Trial found 15% to 20% fewer lung cancer deaths among participants who were screened for lung cancer by low-dose helical CT scans compared to those screened by chest x-ray. Participants included 53,454 current or former heavy smokers ages 55 to 74 between 2002 and 2004.

From this statistic, it would seem obvious that lung cancer screening for older patients who are or were heavy smokers would be a slam dunk. However, the screening does raise some concerns. For instance, some studies show 20% to 60% of screening CT scans of current and former smokers show abnormalities, most of which are not lung cancer. Lung biopsies and surgery do carry risk, yet the uncertainty over having lung nodules might cause considerable anxiety for the patient. How do we determine whether or not to biopsy such abnormalities?

A biopsy of a nodule found by screening could determine if the nodule is cancerous. However, according to the NCI, studies indicate some small lung cancer tumors are indolent – that is, they so slow growing that they never become life threatening. This situation, called overdiagnosis, might cause some patients to be subjected to challenging and potentially damaging lung cancer treatment when they have no symptoms and an extremely low risk of death from lung cancer. Are the risks associated with biopsies and cancer treatment ALWAYS less than the risk of lung cancer death?

Another issue: this new CT screening is recommended only for patient who fit a specific profile (generally, current or former heavy smokers ages 55 to 79).Never smokers and some smokers and former smokers don’t fit this profile, but might have other risk factors for lung cancer. If a patient who doesn’t fit the recommended profile requests a low-dose helical CT scan, and agrees to pay for it, should their doctor agree to order the scan?

A new blood test announced in October (by Bioinformatics for Integrated Diagnostics and the Institute for Systems Biology) can determine if a detected lung nodule is NOT cancerous with 90% accuracy. However, it can’t reliably detect whether a nodule IS lung cancer. Used in combination with CT screening, this blood test might help determine whether a lung nodule warrants a biopsy. Do doctors and patients feel comfortable using a blood test that can say if the patient does NOT have lung cancer, but can’t say if the patient DOES have it?

For those who wish to do more reading

The National Lung Screening Trial: Results are in

Overdiagnosis in Low-Dose Computed Tomography Screening for Lung Cancer

Harmless lung cancer? Many tumors not lethal

Can Lung Cancer be Clinically Insignificant? The Case for “Overdiagnosis” and “Overtreatment” of Lung Cancer

Blood Test Distinguishes Early Lung Cancer From Benign Nodules

A blood-based proteomic classifier for the molecular characterization of pulmonary nodules.

Blood Test to Define Probability of Lung Nodule Being Cancer? Could Help, but Potential to Backfire

National Lung Screening Trial: Questions and Answers

Finding Good Biomedical Science Articles

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Every day patients with cancer and other health issue turn to the Internet to learn about symptoms, causes, and treatments for their conditions. Consumers have many good options for consulting “Dr. Google.” Some websites (like mayoclinic.com) have outstanding credentials for providing medical information. Other sites like PubMed are good places to search for biomedical journal articles.

But not all online biomedical journal articles contain good science.

Science magazine–a premier, peer-reviewed science journal–recently conducted an experiment in which a correspondent submitted a biomedical research paper to open access journals for publication. Open access journals rely on author fees rather than subscriptions. The paper announced a new treatment for cancer derived from lichens. Its science and conclusions were clearly flawed, which should have been caught by each journal’s peer review process. Yet many of the journals published the flawed paper anyway.

This is why I stick to PubMed and journals of demonstrated quality as sources for biomedical articles. It isn’t a foolproof method for finding good science, but it’s better than just googling a topic. You simply can’t believe every headline or abstract you read.

NTRK1: a new oncogene and target in lung cancer

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A new driving mutation in lung cancer called NTRK1 has been found by researchers from University of Colorado and Dana-Farber Cancer Institute. It joins the family of driving mutations like EGFR, ALK, ROS1, and RET. What’s particularly interesting for this mutation is that an exisiting drug appears to target it (in preclinical studies). Note the linked article does NOT say the mutation is specific to NSCLC.

I’m hopeful we’ll have an approved FDA treatment for this mutation more quickly than usual (though I’m not holding my breath).

NTRK1: a new oncogene and target in lung cancer
http://www.coloradocancerblogs.org/ntrk1-a-new-oncogene-and-target-in-lung- cancer/

The Basics of PD-1

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Several clinical trials for lung cancer (as well as other cancers) are pursuing therapies based on the PD-1 pathway of the immune system. These trials can usually be found on clinicaltrials.gov by searching with keywords such as PD-1, PDL-1, or PD-L1. Sometimes these therapies are referred to as anti-PD-1 or anti-PD-L1.

PD-1 (PD stands for Programmed Death) is part of an immune system “checkpoint” pathway that, among other functions, helps turn tumor suppression on or off. PD-1 is actually a protein expressed on the surface of certain cells in our immune system; it is NOT a mutation, but rather something inherent in everyone’s immune system. The cells of interest in these trials are activated T cells, but PD-1 is expressed on other types of cells, too. The PD-1 protein is a receptor, which means another molecule can bind to it.

PD-L1 is a protein of the surface of some (but not all) tumor cells. It is a ligand of PD-1 (hence the “L” in its name), which means it binds to the PD-1 protein. When PD-L1 binds to PD-1, it tells the immune system to ignore the tumor cells. PD-1 has one other known ligand (surprisingly named PDL-2).

PD-1 and PD-L1 therapies aim to blockade the PD-1 pathway so the immune system can better attack cancer tumors. The drugs used are designer molecules that bind to part of the PD-1 pathway and block its activity. Some drugs bind to PDL-1 so it can’t bind to PD-1. Other drugs bind to PD-1 to prevent ligands from binding to it. Both approaches aim for the same effect: keep the PD-1 pathway from telling the immune system to ignore tumor cells.

Not everyone responds to PD-1 pathway therapies. Early trial results show lung cancer patients had response rates on the order of 10% to 18%. Researchers are studying whether biomarkers — proteins such as PD-L1 on the surface of immune system or tumor cells — might indicate which patients will respond well to PD-1 therapies. That is why some trials (but not all) require a biopsy for testing before accepting the patient into the trial.

Since part of the immune response for suppressing tumors involves inflammation, participants in trials based on the PD-1 pathway often find their tumors will grow somewhat when they first start the therapy. A few lung cancer trial patients experienced serious or fatal pneumonitis, a lung inflammation.

PD-1 therapies are promising enough that at least four drug companies (Bristol-Myers Squibb, Roche/Genentech, Medimmune and Merck) are pursuing them in lung cancer trials. Because they modify the immune system, the hope is that these drugs will continue working longer than targeted therapies do.

Please let me know if you find this sort of article helpful.

Edited 2013-09-12 12:53 PM PDT to add information.

Moves in the Cancer Endgame

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My dad taught me to play chess when I was small. I learned the game fast, and could soon beat other kids older than me. However, when I faced an opponent who was much more skilled than I, my attention eventually wandered. I lost the endgame because I’d lost patience.

A chess game transitions to the endgame when few pieces are left on the board. Whatever strategy positioned pieces prior to the endgame becomes irrelevant. The pawns, which initially were the least powerful pieces, become important.

Recently I was playing a much more highly-rated player online (thank you, Nancy Kress) and realized something in my attitude had changed: I had developed patience for the endgame. Even though I had been outmaneuvered and did not possess enough pieces to win, I kept looking for my next move. I wanted to keep the game going as long as possible.

Metastatic lung cancer is a tough opponent, and the odds favor it winning. Several powerful treatments didn’t finish it off. I haven’t many therapy pieces left. But I keep searching for my next move, even if it can’t give me victory. Clinical trials are now my best pieces in the cancer endgame. I want to keep playing — and living — as long as I can.

Cancer taught me patience for the endgame. Maybe someone else will learn from how I played.

Celebrating World Lung Cancer Day

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Today I celebrate World Lung Cancer Day.

Lung cancer claims more lives than any other cancer. According to the American Cancer Society, each year, more people die of lung cancer than of colon, breast, and prostate cancers combined. Yet the survival rate and funding dollars per death are lower for lung cancer than for those cancers (and almost all other cancers). The CDC lists lung cancer (not breast cancer) as the leading cause of cancer death among women.

Lung cancer deserves more research funding. Anyone who has lungs can get lung cancer. About 60% of newly-diagnosed lung cancer patients are non-smokers or never smokers, and lung cancer in never-smokers ranks among the top 10 fatal cancers in the USA. And, regardless of one’s habits or behaviors, NO ONE deserves to die of lung cancer.

Already more metastatic lung cancer patients like me are living longer thanks to targeted therapies, maintenance chemo, and changes in standard of care. Lung cancer statistics will continue to improve as more patients start to benefit from upcoming early detection methods (like CT screenings and biomarker testing), improvements in treatment options, and an increased national focus on lung cancer research.

Here’s hoping for more successful treatment options for all lung cancer patients, and a cure in my lifetime — which means SOON.

LUNGevity announces its 2013 Research Awards

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I received the information below in a news release email from LUNGevity today. It’s encouraging to see the research undertaken for lung cancer patients, especially research related to the KRAS mutation (for which few therapies currently exist), lung cancer resistant to radiation therapy, and acquired resistance to targeted therapies (like Tarceva).

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LUNGevity is proud to announce our 2013 Research Awards!

New LUNGevity awards are enabling promising research into managing lung cancer treatment more effectively, as well as preventing the disease in high-risk populations.

Six exceptional researchers have received 2013 LUNGevity Lung Cancer Research Awards. They join a community of brilliant LUNGevity-funded scientists across the country who are working to help people with lung cancer live longer and better.

 

2013 Career Development Awards for Translational Research were made to the following researchers.

Timothy Burns, MD, PhD, University of Pittsburgh Cancer Institute, is working on targeted therapy for non-small cell lung cancer (NSCLC) patients with mutations in a gene called KRAS, using a new class of drugs.

David Kozono, MD, PhD, Dana-Farber Cancer Institute, will identify which genetic types of lung cancer are the most resistant to radiation, and which of these may be best treated with a combination of radiation and bortezomib, a drug already FDA-approved for another type of cancer.

Meredith Tennis, PhD, University of Colorado Denver, will identify biomarkers that signal whether a patient is likely to benefit from iloprost and pioglitazone, two drugs that have demonstrated promise in reducing NSCLC risk, and whether they work in a clinical trial setting.

 

2013 Targeted Therapeutics Awards for Translational Research were made to the following researchers.

Balazs Halmos, MD, Columbia University Medical Center, is working on a way to increase the effectiveness of radiation and chemotherapy that could also lead to personalized NSCLC treatments, especially for the third of all lung cancer patients with locally advanced lung cancer.

Lecia V. Sequist, MD, Massachusetts General Hospital, will develop models that explain how NSCLC patients can acquire drug resistance to targeted therapies after a period of initial successful treatment, leading to the development of new treatments to help patient overcome the drug resistance.

Frank J. Slack, PhD, Yale University, is studying the KRAS-variant, a recently discovered KRAS mutation found in over 20% of NSCLC patients, which has been shown to predict a patient’s response to cancer treatment. His research aims to confirm the role of the KRAS-variant to direct cancer therapy for lung cancer patients and as a potential future target for therapy.

 

The work of these talented researchers will help ensure continued progress in fighting lung cancer. Special thanks to Genentech and our other donors for their support of the LUNGevity Scientific Research Awards Program. Read more about these exciting projects. In addition to these awards, LUNGevity will announce funding for awards through its Early Detection Awards Program later this year. Please stay tuned!