Gilotrif approved as treatment for advanced lung cancers driven by EGFR mutation


Elizabeth whittington blog image
Gilotrif, also known as afatinib, is now approved to treat patients with metastatic non-small cell lung cancer (NSCLC) that have an EGFR gene mutation. The drug was approved quickly by the Food and Drug Administration under the agency's priority review program because of the aggressive nature of NSCLC, and the fact that there are few treatment options for patients with this type of cancer.

[FDA: FDA approves new treatment for a type of late-stage lung cancer]

NSCLC is the most common type of lung cancer, but EGFR mutation-positive lung cancers account for about 10 percent, which still means that thousands of patients may potentially benefit from the new drug.

In addition to the drug approval, the FDA also approved a diagnostic test that identifies lung cancers with the EGFR mutation. The practice of approving therapies with a specific diagnostic test is something we may be seeing more of in the future. Tarceva (erlotinib), a lung cancer drug that also targets the EGFR mutation, was approved in May to treat patients with newly diagnosed NSCLC, along with a separate EGFR test. (Tarceva was previously approved for second-line NSCLC and as maintenance therapy.)

"Companion diagnostics are a fundamental element of personalized treatment for cancer and other diseases," said Tadd Lazarus, chief medical officer of Qiagen, the company that developed Gilotrif's companion diagnostic test, in response to an email question. "Diagnostics such as therascreen EGFR can identify patients who are most likely to respond to treatment and avoid ineffective, expensive and potentially harmful medical care."

Lazarus added that "Within the next five to 10 years, all new oncology drugs will have a companion diagnostic," according to a report from Tufts University in Boston.

The drug, which is taken orally, was approved based on a large-scale phase 3 clinical study called LUX Lung-3, which compared Gilotrif with (Alimta) pemetrexed and cisplatin. Of the 345 participants, those who received Gilotrif delayed cancer growth a median of 4.2 months (11.1 months versus 6.9 months). In a group of participants who had the most common types of EGFR mutations, such as exon 19 deletion, the delay in progression was nearly double with Gilotrif (13.6 versus 6.9 months). Reports also show that quality of life was better in the investigational arm.

A benefit in overall survival was not seen, but participants in the chemotherapy arm may have received another EGFR-targeted therapy after their disease progressed. Results were announced last year at the annual meeting of the American Society of Clinical Oncology (ASCO) [CURE: Afatinib Helps Delay Lung Cancer Progression].

Studies do suggest that Gilotrif blocks the EGFR pathway for a longer period of time than Tarceva. The drug also inhibits the HER2 pathway, a mutation that is sometimes seen in breast and gastric cancers. The next step may be to compare Gilotrif with the other EGFR-targeted therapies, Tarceva and Iressa (gefitinib). The LUX-Lung 7 trial will compare Gilotrif to Iressa.

Side effects of Gilotrif include diarrhea, skin issues, inflammation in the mouth, throat or lung, and liver toxicity.

For more information on EGFR mutation-positive lung cancer, Cancer.Net (ASCO's patient website) explains the importance of testing for the EGFR mutation and what it means for treatment options.

Afatinib is also being examined in head and neck cancers, gliomas and other solid tumors.


Do you talk to your doctor about cost of care?


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Cost is one of those "difficult conversations" between a patient and a physician, right up there with end-of-life discussions. Does that surprise you?

An article posted online from the Journal of the American Medical Association addresses the issue of medical cost in "First, Do No (Financial) Harm."

"... seemingly simple decisions that physicians make about testing could directly lead to thousands of dollars in out-of-pocket costs," the authors write, noting that physicians shouldn't assume that high medical costs are a known and unavoidable fact of life for all patients. The article encourages physicians to optimize care for individual patients in regards to cost, a strategy used commonly to treat cancer. The article is geared toward a general medical audience, not specifically cancer, so the examples it provides may not apply. However, the overall theme is that physicians should have a financial conversation with their patients, including if patients are worried about cost and are understanding the financial ramifications of screening and treatment.

"Too often physicians choose less than ideal options for their particular patients not due to a lack of caring, but rather a lack of knowing. This includes not prescribing generic or other insurance-covered drugs when appropriate. Lack of awareness about the opportunities to provide higher-value care should no longer be an allowable excuse."

While the article is geared toward physicians having that financial conversation with their patients, this should also encourage patients to initiate the discussion. Asking for lower cost treatment alternatives, generics or making sure their doctor works within their insurance plan are conversations that patients shouldn't be ashamed to have with their physicians.

At the annual meeting of the American Society of Clinical Oncology this year, a study examined how likely insured patients were to talk to their physician about treatment cost. Nearly half of the 119 patients surveyed expressed a desire to discuss the issue, but only 21 percent had actually done so. Of that 21 percent, half felt the discussion helped lower their treatment costs.

In another study of women with breast cancer, 94 percent believed cost should be discussed between patient and physician, but only 14 percent reported ever having the discussion.

"To provide truly patient-centered care, physicians can live up to the mantra of 'First, do no harm' by not only caring for their patients' health, but also for their financial well-being," the authors conclude.

Do you discuss cost with your physician? And does cost affect your treatment decisions?

Stay tuned for more on this subject. CURE is producing a supplement on the cost of cancer care later this year, which will include tips and resources to help manage the financial burden of cancer.


Are you biased when it comes to lung cancer?


Elizabeth whittington blog image
After having a close family member diagnosed with lung cancer, I feel that no one deserves cancer – especially one that carries the stigma of lung cancer. Which is why I was surprised that, after taking The Lung Cancer Project test, it showed I still had a negative bias against lung cancer, more so than another cancer type. Even with new treatments and potentially better screening, I had seen firsthand how dreadful the disease could be.

The Lung Cancer Project tests people's subconscious perceptions or hidden biases of breast and lung cancers. It also poses the question of whether these perceptions and biases influence treatment decisions.


The Lung Cancer Project is a research study that examines the "social psychology" of lung cancer through an Implicit Association test. The test gives the user rapid-fire tasks of associating images and words with either lung cancer or breast cancer. If you subconsciously relate a certain image or word, such as "hopeless," to lung cancer, you will probably complete the task faster than when the word is associated with breast cancer. The test takes about 10 minutes to complete, and gives you your results at the end.

The rapid tasks in the survey make it easier for any slight hesitation to be picked up, which will then be calculated into the final score at the end. Of the 1778 responses, researchers found that on average, participants responded faster when lung cancer and a negative word were associated than with breast cancer.

Joan Schiller, a lung cancer specialist at University of Texas Southwestern Medical Center in Dallas, explained the purpose behind the study: "The idea was to quantify and improve upon what we've felt in the past ... that lung cancer patients suffer from guilt, stigma and shame. There hasn't been a way to quantify it or prove that it's been an issue," she says. "This project has led to a benchmark to measure it."

With the results of the study, which were published at the annual meeting of the American Society of Clinical Oncology in early June (Poster #8017), Schiller and others hope to be able to measure progress in the coming years about people's perception of lung cancer. She also hopes that it will be the first step in learning why a majority of individuals diagnosed with advanced lung cancer never receive treatment. Is it due to the perception that treatment is futile? Or that they deserved the disease? Guilt?

The project is the result of a partnership with Genentech, a pharmaceutical company that manufacturers a lung cancer treatment, Project Implicit and various non-profit lung cancer organizations, including the Lung Cancer Alliance and the National Lung Cancer Partnership.

Schiller has been instrumental in promoting lung cancer awareness and research in her role of lung cancer researcher, but also as president and founder of the National Lung Cancer Partnership. "When I went into the field, there weren't a lot of people going into lung cancer for exactly the same reason – it wasn't popular because of the lack of treatments, research and funding."

Take the test and ponder your results. The full results can be viewed in the following infographic.


Median survival of one month – whoop de doo


When I first started reading studies, I remember reading one in particular and everyone was really excited about the fact that it offered an increase of four months of median survival time.

That didn't seem like a lot to me, until I understood what it meant.

Median survival means that there were some patients who lived much longer on the drug, and some who lived a much shorter time on the drug. To be more specific, four months of median survival time means that half of the patients on the treatment died before four months, but also that half of the patients lived beyond four months; some may have lived much longer than four months. Looking at the actual study can illustrate this effect.

Also, unless you have the whole study in front of you, what you don't know is how sick the patients were who took the drug, and that's important. New drugs are often given to patients who have no more options for the obvious reason that they are not going to give an experimental drug to a patient who could get some response from a drug that has shown efficacy.

Another aspect you have to take into account is the patient. What we are learning is that in each group of patients who take a drug, there may be one or two who respond very well. For some reason unknown to anyone, one or two patients may have a great reaction to the drug and their cancer may go into remission or reduce in size.

When these cases are thrown in with the others, it skews the results, but it also makes news and sometimes results in the study being stopped early so the drug can be given to more patients who have one or two similarities that indicate they may respond to the drug.

Right now researchers are trying to find those small pools of patients who respond to certain drugs and single them out. It's the reason that many patients now get a cocktail of chemotherapy drugs instead of just one. They may have one drug that covers all dividing cells and then one that only targets a particular protein known to help that one kind of cancer grow. It gets very complicated.

So, when you hear of a drug showing a median of three months of extended life, look at the surrounding information in the study. Did one patient live a year? Did one have a remarkable response that calls for further investigation?

You may remember the big noise around Avastin when the powers that be wanted to remove it from metastatic breast cancer use. Well there is a subset of women for whom Avastin works wonders. They didn't want it removed for obvious reasons. But there are very few of them.

And as my friend Suzanne Lindley says, even if it is only six months you get, that's half a year and two seasons to watch a 4-year-old begin to notice new things in her life and have new memories. Six months is a lot of live when you are facing not having it.


From ASCO: Updates in HER2-positive breast cancers


Debu Tripathy blog image
Debu Tripathy, MD, editor-in-chief of CURE, discusses preliminary studies on combining Herceptin (trastuzumab) with existing drugs to treat HER2-positive breast cancer. These highlighted studies were presented at the 2013 American Society of Clinical Oncology's annual meeting in Chicago.


Avastin fails to provide benefit for patients with newly diagnosed glioblastoma


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A disappointing showing of a phase 3 study found that Avastin (bevacizumab) in newly diagnosed glioblastoma did not prolong survival. The study was presented as one of the headlining studies in the Plenary session at the annual meeting on Sunday.

Glioblastoma is an aggressive, hard-to-treat brain tumor that affects about 10,000 people at year in the U.S. Average survival for this type of brain tumor is fewer than 18 months, and is treated with a variety of radiation, surgery and chemotherapy, including temozolomide.

Avastin was granted accelerated approval for treatment of recurrent glioblastoma in 2009 due to promising phase 2 studies that showed the drug delayed disease progression. This makes sense because the tumor is highly vascular, sending out proteins to encourage blood vessel growth to the tumor to help grow--a process called angiogenesis. Avastin, which blocks the pathway involving this protein, called vascular endothelial growth factor, would be a logical choice to treat newly diagnosed glioblastoma. The thought was the earlier you treat this tumor with an anti-angiogenic therapy, the less lethal it would be.

With that in mind, the drug is sometimes used to treat newly diagnosed patients in the hopes that the same effect seen in recurrent glioblastoma would apply to this patient population.

Unfortunately, that's not the case. This latest large-scale phase 3 study, which was to confirm the effectiveness of Avastin and possibly improve survival, actually found that the drug conveyed no benefit. Survival was 16.1 months in the placebo arm and 15.7 months in the Avastin arm. Progression-free survival was 7.3 months and 10.7 months, respectively. Although the trend was toward Avastin, the difference could be just due to chance (not statistically significant.) Patients who were randomized to receive Avastin also had more side effects, including low platelet counts, which can contribute to bleeding problems, as well as blood clots and high blood pressure.

The study was designed to look for overall survival and progression-free survival at the same time, which was interesting (usually it's one or the other). The researchers required tumor tissue samples to provide molecular testing, which will be helpful in the long run, because they are looking for any sign that Avastin may work in a certain group of patients. They also recorded patient outcomes, symptom burden, quality of life and cognitive function.

How do these results compare to another phase 3 study in newly diagnosed glioblastoma patients? The AVAglio trial data released last year found that the addition of Avastin to temozolomide and radiation delayed progression-free survival, but no difference in overall survival has been seen yet. There are slight differences in the trial, so researchers are watching the two studies closely to gain additional insight and data on different subsets of patients.

Unfortunately, the past few phase 3 studies in brain cancer have all been disappointing, ranging from the Avastin trial to cilengitide to cediranib.

It's important to note that these results do not affect the use of Avastin in recurrent glioblastoma.


Nexavar halts thyroid cancer progression for five months


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Every year, about 60,000 Americans receive a diagnosis of thyroid cancer. The kinase inhibitor Nexavar (sorafenib), already approved for kidney and liver cancers, has been shown to keep thyroid cancer from progressing for five months, according to results of a phase 3 study presented at ASCO's annual meeting.

Although thyroid cancer is highly curable with surgery and radioactive iodine treatment, the disease becomes resistant to therapies in about 10 percent of patients, often metastasizing to the lymph nodes, lungs, bones and other sites. For nearly four decades, the only approved treatment for patients whose disease had progressed was doxorubicin, which was avoided because it was ineffective and highly toxic.

The multicenter, international DECISION trial included 417 participants with advanced differentiated thyroid cancer that had progressed within the prior 14 months on radioactive iodine. Participants were randomized to take Nexavar or a placebo. Those in the Nexavar group experienced greater tumor shrinkage (12 percent versus 0.5 percent), a higher rate of stable disease (42 percent versus 33 percent at six months), and a longer period of time to disease progression (10.8 versus 5.8 months).

Side effects were similar to those experienced by patients taking Nexavar for liver and kidney cancers: rash, fatigue, weight loss, hair loss, hypertension and diarrhea.

Of the four types of thyroid cancer (papillary, follicular, medullary and anaplastic), the vast majority (80 to 90 percent) of cases are papillary and follicular--the types Nexavar targets. Affecting more women than men, thyroid cancer is the fastest-increasing cancer in the U.S.


Small gain in ocular melanoma equals big news


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In a cancer that doesn't have many treatment options, any gains are considered a success.

Uveal melanoma, although rare, is the most common eye cancer in adults, affecting nearly 2500 individuals a year. While surgery and radiation are standard treatments, once the disease becomes metastatic it is almost impossible to treat successfully.

Researchers decided to test a MEK inhibitor, selumitinib, in this patient population. The thought was that because most of these tumors express a certain gene mutation it would respond to this particular targeted drug.

No standard treatments exist, which made a control group hard to create, says lead author. Instead of making it a placebo-based trial, researchers compared the MEK inhibitor with a temzolomide, a brain cancer drug that has been used to treat skin cancers.

Details of the clinical trial can be found at

You can find out more about ocular melanoma at the Ocular Melanoma Foundation You can read more about the study at ASCO.

Richard Carvajal
Richard D. Carvajal, MD, a medical oncologist at Memorial Sloan-Kettering Cancer Center describes the results of the selumetinib study. Photo by ©ASCO/Scott Morgan 2013


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