When I wrote my first review article on the treatment of the elderly, I entitled it, “NSCLC in the elderly—the legacy of therapeutic neglect.” Dr. Corey Langer and I chose the title to directly criticize the major mistake that we perceive in the treatment of the fit elderly—a therapeutic nihilism that leads oncologists to not give sufficiently aggressive treatment to the fit elderly. Lung cancer is a terrible cancer and failure to suppress it with sufficiently active therapy leads to great suffering. This is as true in the older patient as in the younger patient. However, there is great misunderstanding about the efficacy of therapy in the fit elderly patient, the subject of this post. I will seek to summarize coverage of this topic on GRACE previously, highlighting the now published French data on 1st line treatment of the elderly. You may have noted the repeated use of the word, “fit.” Not all elderly patients are as fit as younger patients—aging brings with it more medical problems and more pills; not all elderly patients are as fit as younger patients with lung cancer. I will address this topic in a follow up post dedicated to this important topic.
Thoracic Oncology is Geriatric Oncology:
The average age of presentation of metastatic lung cancer is 71, so the elderly are not a fringe group in lung cancer, but rather the majority. This number is expected to rise. What is elderly? Personally, I think that elderly is anyone at least 20 years older than me, or perhaps someone without a smartphone. But, functionally for my trials, I define, “geriatric” as at least 70 years of age.
One reason that some doctors under treat the elderly is the mistaken belief that they don’t have much life left anyway. Life expectancy by age has been well studied. The data below from the National Center for Health Statistics from 2005 summarize life expectancy based on age and gender:
Age Men Women
60 20.8 24
65 17.1 20
70 13.7 16.2
75 10.7 12.8
80 8.2 9.8
85 6.1 7.2
90 4.4 5.2
95 3.2 3.7
100 2.4 2.6
Our average 70 year old man can expect to live 14 years and our average 70 year old woman can expect to live 11 years, if not for lung cancer. Because lung cancer tends to be aggressive, the success of controlling lung cancer will drive both quality and duration of life for the fit elderly patient.
1st Line Therapy in the Elderly
Dr. West did the heavy lifting for me on this one, and I refer you to his excellent post, Does Age Matter? Treating Older Patients with Advanced NSCLC, for background on older trials (pun intended). You can read the full post for details, but I’ll give you a quick summary of the results of older trials. First, older patients do benefit from chemotherapy. Most famously, the ELVIS trial showed that navelbine was better than no chemotherapy for overall survival, quality of life, and nonprogression of lung cancer-related symptoms. Next, two drugs were compared to one. Although two drugs were not better than one, it is notable that the second drug in this study (called MILES, also very famous in our world) was not a platinum drug (cisplatin or carboplatin)—our standard of care for younger patients is the combination of a partner drug and a platinum drug, not two partner drugs.
This question was recently addressed in two phase III trials. The first compared 1 drug (doctor’s choice of gemcitabine or vinorelbine) to a platinum doublet (carboplatin and paclitaxel). Dr. West reviewed the results of this trial at the time of presentation at ASCO in his article, Doublet vs. Single Agent Chemo in the Elderly with Advanced NSCLC: France Offers a Definitive Answer. The trial randomized 451 patients to one drug vs. two drugs. The average age of patients was 77. Patients had to have performance status 0-2, which means that while they couldn’t be super-sick, the trial didn’t cherry pick for the best patients. In the figure below, overall survival is shown at the left and progression-free survival at the right. You can see clear superiority for the doublet, adding further evidence to the idea that the fit elderly benefit from standard of care chemotherapy.
Not surprisingly, toxicity was worse with two drugs than it was with one drug:
The most remarkable exacerbation of toxicity was neutropenia. With two drugs, the grade 3/4 neutropenia rate was 48.4%, compared to 12.4% with one drug. This is a very high rate of severe neutropenia. It translated to a 9.4% rate of febrile neutropenia, compared to 2.7% for one drug. I’ve pointed out on GRACE before that the goals of treating incurable lung cancer are twofold: Increase duration of life and increase quality of life. The authors clearly met the first of these two goals. But did the increased toxicity cause more suffering than it prevented? The authors did quality of life analysis which showed globally similar quality of life in both groups, with some differences in the composition of symptoms. As full data on this is promised at a future point, I will defer commentary until it is published. For now, I will say that based on the data we have, it seems that the toxicity of adding a second drug was about equally balanced by preventing symptoms of progressive lung cancer. Some international experts nay-sayed these results pending publication, but I hope that publication of these results lead more oncologists to give the fit elderly doublet therapy.
The second trial used a regimen that in my opinion was a less optimal choice for the elderly. This trial compared single-agent docetaxel every three weeks to weekly cisplatin plus weekly docetaxel. Cisplatin, compared to carboplatin, is a much rougher drug and docetaxel, compared to paclitaxel, is a rougher drug. This trial, in contrast to the last one, was negative and had high rates of side effects. While some argue that this trial provides evidence against the benefits of giving the elderly two drugs, I believe that it shows us to use carboplatin (and not cisplatin) and paclitaxel (and not docetaxel) for most elderly patients.
Second Line Treatment in the Fit Elderly
Here again, Dr. West has done the heavy lifting. In 2008 he summarized the available data in Second Line Treatment In Elderly Patients. To my mind, there are two key studies for us to talk about today. The first looked at patients 70 and older enrolled on a larger study of pemetrexed vs docetaxel for 2nd line NSCLC.
First, we see that the elderly benefitted from chemotherapy and seemed to do so to a similar extent as younger patients. However, toxicity was worse, including neutropenia.
The second trial compared tarceva to placebo in second line therapy. There were 163 elderly patients on the trial, allowing for subset analysis. While the elderly patients had more side effects with treatment than younger patients, they did benefit from being treated.
I have not addressed here adjuvant therapy in the elderly, but rather refer the curious to Adjuvant Therapy in the Elderly and/or Frail: Podcast of Discussion with Dr. Hesketh and Kelly. Perhaps even more notably, this post addresses only the fit elderly. While I know many older people, including some with lung cancer, who are extremely fit, this is certainly not true of all patients. We’re not ignoring this subject on GRACE, and it will be the topic of a future post. Also, I’m looking to arrange some content on breast cancer in the elderly; I’ll keep you updated as plans for this come together.