By BISHAL GYAWALI MD
Long list of news in lung cancer
September was an important month in oncology—especially for lung cancer. The World Conference in Lung Cancer (WCLC) 2018 gave us some important practice-changing results, also leading to four NEJM publications. The trial with most public health impact is unfortunately not published yet. It’s the NELSON trial that randomised more than 15000 asymptomatic people at high risk of lung cancer to either CT-based screening for lung cancer or to no screening and found a significant reduction in lung cancer mortality rates among the screened cohort compared with the control cohort. This reduction was more pronounced among women, although they constituted only 16% of the trial population. I am looking forward to reading the full publication and am particularly interested in knowing if there were any differences in all-cause mortality rates and the rates of overdiagnoses.
A new ALK-inhibitor on the block—brigatinib—has significantly improved PFS versus crizotinib when used as first-line therapy in ALK-positive non-small cell lung cancer (NSCLC) patients. However, I assume that it will be difficult for brigatinib to replace alectinib in this setting, since the latter has already been tested in two different RCTs and has more mature data.
With Keynote 407, pembrolizumab has entered into the treatment arsenal for squamous NSCLC by improving overall survival in combination with chemotherapy versus chemotherapy alone as a first-line regimen. However, when A B is compared with A, it is important to know whether A B is better than A followed by B. In this trial, 32% of patients who were in the control arm received a PD-1 inhibitor upon progression. Nivolumab is already approved as a second-line option in this setting after first-line chemo; so how much benefit in Keynote 407 is due to more than half of control arm patients not getting PD-1 inhibitor at all versus the benefit of combining pembrolizumab with chemo upfront is an important question.
A friend of mine has been living well with lung cancer for five years — working, running several miles a day, traveling, doing good stuff with his family, and generally enjoying the pleasures of everyday life. He knows the cancer will eventually kill him, but has been making the most of every remaining minute.
Then, a month ago, things suddenly turned dramatically south. Severe shortness of breath, constant coughing, sleeplessness, fatigue, loss of interest, anxiety. My friend figured the jig was finally up — that he was going terminal. We all felt sad in the face of this inevitability. In our different ways, we began the painful process of saying goodbye.
Then things seemed to get even worse. I accompanied my friend to visit his lung doctor — an amiable and thorough man who spent lots of time with us, took a good history, and did many tests.
About three years ago, a new member of our Lung Cancer Survivors Support Community posted a message: she was taking Tarceva and wanted to discuss with fellow members everything about that cancer drug.
She titled her post, TARCEVA DIVAS AND DUDES DISCUSSION & SUPPORT. She saw a need to create a community within a community, and beginning with that modest post, she did it. She didn’t ask permission. She didn’t wait for us, or another member, to organize and lead a top-down discussion about Tarceva.
The ongoing discussion string became the place for our members to go to talk about Tarceva and next-generation lung cancer treatments.
The member became known by some as the Tarceva Diva, and for the purposes of this story, that’s what I’ll call her. This story is not specifically about Tarceva, or even about lung cancer, but instead, it’s a celebration of an unsung hero who helped thousands of people.
There have been well over 8,000 posts in less than three years’ time–about 250 posts per month–in just that series of hundreds of “Divas and Dudes” discussion strings. That’s a constant, dedicated stream of treatment insights from-the-front-lines of people worldwide affected directly by lung cancer.
“WELCOME TO TARCEVALAND!!!” she’d proclaim to a new member, or “newbie.” She could insert humor into the discussions without making light of the seriousness of members’ illnesses. The activity in the Tarceva sub-community grew so quickly that the Tarceva Diva created another discussion topic, TARCEVA SIDE EFFECT BUSTERS, which created yet another resource for members.
Thursday I traversed the frozen surface of the pond for perhaps the last time this season. The ice is thinning quickly. I had on my rubber boots and stayed what I felt to be a safe distance from shore: should I break through, the water would not be over my head. I got some fantastic photos and considered the little adventure a success. However, over dinner that evening when I mentioned that I’d been on the pond earlier, David and Peter were furious. Peter wouldn’t calm down until I promised I wouldn’t go out again.
I have always considered fear the enemy; something to conquer and overcome and I’ve had a lot of practice. Being risk adverse and scrappy has been an asset now that I have lung cancer. As a participant in a phase I clinical trial, there is the potential for unforeseen and possibly life threatening side effects of treatment itself. Before you are given your first dose of an experimental drug, you must read through and sign consent forms which acknowledge this risk. It is something most healthy persons would never do. When you have a terminal illness, it is similar to coming to the edge of a ravine with a tiger on your trail. Between you and safety is a rickety bridge that may or may not support your weight. However, even chancy passage is an easy decision when the alternative is certain death.
Universal treatment standards will be the basis of future medical care. In oncology, a leading organization for the development of such guidelines is the National Comprehensive Cancer Network (NCCN). This national consortium of 21 National Cancer Institute designated cancer centers publishes state of the art recommendations. Modified continuously, these are internationally respected guidelines and cover more then 97% of cancers.
The 17th Annual NCCN Conference was held in Hollywood, Florida last month. Cancer guidelines were updated in several significant ways.
The general movement of the last 20 years has been to reduce the amount of surgery for breast cancer. The NCCN recommends that during breast saving surgery (lumpectomy) the surgeon test the first lymph node (“sentinel”). If there is no cancer in the first one or two nodes, then no more nodes need to be removed. The NCCN also stated, that if breast cancer patients have small cancers and normal blood tests, they do not need a bone scan, or CT scan.
In lung cancer patients, several procedures received new support. It is recommended that doctors use ultrasound-guided biopsy to sample lymph nodes in the middle of the chest (mediastinum) instead of surgery. The new guidelines also support the use of non-invasive surgery (Video Assisted Thorascopic Surgery, VATS) instead of open surgery to treat lung cancer. The use of VATS for lung cancer has increased more than 300% in recent years. The pathologic name for an increasingly common form of lung cancer was changed. Formally, called “bronchioalveolar”, it will now be called “adenocarcinoma in situ.” Finally, the NCCN emphasized the need for accurate genetic testing for “ALK”, before using the drug that targets this mutation, crizotinib.
Recently a patient with advanced lung cancer was admitted to a local hospital. Pain in his abdomen was diagnosed as a gallbladder infection.
Because he had metastatic cancer, in addition to the new problem, the patient and family decided that if things deteriorated he should not be given CPR or put on a respirator. A Do Not Resuscitate (DNR) order was entered in his chart. Treatment for the gallbladder was continued, but it was decided that there was a line that the doctors would not cross.
This made sense to me.
Try conventional therapy, but if he was too weak to recover, then do not continue treatment which could cause more suffering than benefit. Give him the opportunity to survive the gallbladder problem, but respect the terminal nature of the greater disease. We were all gratified when his pain and fever went away, and he recovered from the emergency.
When we were discharging him from the hospital, a surprising thing occurred.
The patient and family requested that since he had survived the infection, that the DNR be reversed. They decided that when a sudden new major medical complication occurred, that CPR be performed and he would be placed on a respirator. The clear protective line vanished.
In difficult lengthy discussions with the patient and family, it became clear that they were riding tides of emotion. When things looked better, they focused on life and “cure.” When things grew worse, they were ready to withdraw. They became defensive and angry at the suggestion that this decision might cause suffering. We were not able to redefine limits to his care.
It is not a secret that I dislike tobacco companies. Intensely. I do not see the point of allowing them to sell a product whose value is all in the negative. I am appalled that we are looking for expensive ways to diminish lung cancer mortality before considering a complete ban on this disease promotion apparatus. Yet this story in the LA Times got my goat. Briefly, a woman who has smoked for years and has had smoking-related obstructive lung disease since 1989 decided to sue tobacco companies after developing lung cancer in 2003. The suit has been making the rounds in various levels of courts, since the defendants asserted that she had exceeded the 2-year statute of limitations following the onset of her smoking-caused disease, referring to the 1989 COPD diagnosis. However, the California State Supreme Court has ruled that she can still sue the manufacturers, since she filed her suit within two years of the lung cancer diagnosis. So, why am I bothered?
Well, here is the thing: once you develop lung disease, followed by periodontal disease, as this woman did, had she really remained unaware that cigarettes are bad? That they cause problems? Is it really possible to live in our world and NOT be aware that tobacco kills? And if she was aware and continued to smoke, whose responsibility is it that she developed lung cancer, hers or the manufacturer’s? Well, you say, but the tobacco companies are unethical and lied about making cigarettes more addictive by adding undisclosed ingredients. So, how are we, the consumers, to know? Well, this is pretty simple: We have free will, don’t we? And if you have the free will, you have to exercise some will power, no? Is this not what the human condition is all about? Continue reading…