Article and Video CATEGORIES

Cancer Journey

Search By

Dr. Jack West is a medical oncologist and thoracic oncology specialist who is the Founder and previously served as President & CEO, currently a member of the Board of Directors of the Global Resource for Advancing Cancer Education (GRACE)

 

Chemo Combinations for Advanced NSCLC: A Regimen of Choice, or a Choice of Regimens?
Author
Howard (Jack) West, MD

We've come along way over the past decade. In the first half of the 1990s, the value of treating metastatic NSCLC was debated and not clear. A "meta-analysis" that pooled the results from 11 chemotherapy trials, 8 with cisplatin, and nearly 1200 patients demonstrated a modest but convincing improvement in survival compared to supportive care alone (article here). The figure summarizing the improvement by adding chemo is shown here:

Adv NSCLC BMJ Meta-Analysis (click to enlarge)

Although the difference now seems pretty convincing to me, and probably to you, at a time when treatment for advanced NSCLC was otherwise not felt to be beneficial, these results didn't take the world by storm. Fortunately, several new drugs emerged for lung cancer that were often well tolerated and had clear activity in lung cancer as single agents:

Newer Agents in Adv. NSCLC

In oncology, if we see a benefit from cisplatin, and a suggestion of a benefit from one of these newer agents, our next step is to check whether the combination is better than one drug alone. So several trials after that were conducted that randomized people with advanced NSCLC to either cisplatin alone or cisplatin with another chemo drug, and these trials showed a clear benefit in response rate and survival for the doublets:

Doublets Over Singlets in NSCLC

So we had several platinum-based doublets, several companies with new drugs that were all convinced their drug was the best to add to a platinum. At the same time, in addition to cisplatin, which was the old standard chemo drug for lung cancer, a newer cousin of cisplatin, known as carboplatin, also became available as a potentially suitable alternative to cisplatin, but with different and generally fewer side effects. It was time for a showdown!

The Eastern Cooperative Oncology Group (ECOG) developed a trial that would directly test four different chemo regimens against each other. This trial, known as ECOG 1594 (abstract here), compared cisplatin and paclitaxel (taxol) to cisplatin with docetaxel (taxotere) or gemcitabine (Gemzar), and a fourth arm with carboplatin replacing cisplatin in combination with taxol:

ECOG 1594 Schema

So this trial, with just over 300 patients on each arm and 1207 patients in total, would give us the answer to the question of what is the best two drug combination for advanced NSCLC. The results were clear:

ECOG 1594 Survival Curves

Unfortunately, the answer was that all of the four combinations gave literally superimposable results. There were no meaningful differences among the groups across the main efficacy endpoints:

ECOG 1594 survival results

The only endpoint that met statistical significance was the progression-free survival of cisplatin-gemcitabine arm being about a month longer than the other arms. One issue, though, is that the cisplatin/gemcitabine treatment cycle was for four weeks, while the others were for three weeks, which meant that the follow-up scans after two cycles were two weeks later with that arm, so this makes the importance of this difference pretty questionable. The other issue is that the importance of a difference of a few weeks in progression-free survival is probably not a clinically significant difference compared to living longer or having fewer side effects. And there were only mild differences in side effects, overall favoring the carboplatin/paclitaxel arm, as we might have expected.

Over the past several years, many other trials have compared one doublet combination to another, and while there have been a few that showed minor differences, overall these trials have shown that they all perform remarkably similarly. There is no regimen of choice, but rather a choice of regimens, to be based on issues like particular side effects to avoid or schedule (some administer chemo once every three weeks, some on a weekly basis), and a physician's experience and comfort with a regimen (it's generally helpful to have an oncologist who is quite familiar and comfortable with the regimen you're getting). And they're all an appropriate option.

The one monkey wrench is the that Avastin was added to the carboplatin/paclitaxel regimen in the 4599 trial and shown to have a survival benefit in certain patients (see post reviewing this trial here). While I suspect that the survival benefit from Avastin will eventually be shown to exist when it is given with other chemo combinations, the US FDA approval is with carboplatin/paclitaxel. Because serious and even fatal toxicities can occur with Avastin even when used by the book, and we don't have as much experience with different chemo combinations with Avastin, I choose to use carboplatin/paclitaxel with avastin for patients who are eligible and want to pursue this approach. For people who aren't receiving avastin, I often give carboplatin and gemcitabine, which I find to be especially well tolerated by a majority of patients, but there's no one best choice when they all achieve very similar results.

Next Previous link

Previous PostNext Post

Related Content

Image
Lung Cancer OncTalk 2023
Video
At our live event, Lung Cancer OncTalk 2023, Dr. Jeff Yang, discusses different surgical procedures used to treat early-stage lung cancer and different approaches to removing cancerous tissue from the lung. 
Image
Lung Cancer OncTalk 2023
Video
At our live event, Lung Cancer OncTalk 2023, Dr. Millie Das, discusses different Studies and Trials for NSCLC. Dr. Das specializes in the treatment of thoracic malignancies. She sees and treats patients both at the Stanford Cancer Center and at the Palo Alto VA Hospital. She is the Chief of Oncology at the Palo Alto VA and is an active member of the VA National Lung Cancer Working Group and Lung Cancer Precision Oncology Program. Learn more about Dr. Das here.
Image
The Importance of Early Detection 2023
Video
Drs. Meredith McKean, Dr. Doug Micalizzi and patient advocate and lung cancer survivor, Ivy Elkins, discuss the importance of early detection and treatment across cancer types, including skin, lung, and breast. To watch the complete playlist click here.

Forum Discussions

Hi Blaze,

 

As much as I hate to say it, Welcome back Blaze.  It sounds like you're otherwise feeling good and enjoying life which is a wonderful place to be. ...

Waiting for my appointment with oncologist this morning. Thank you for the response. It helps. <3

It sounds like you’re thinking of this in a very appropriate way. Specifically, it sounds like the growth of the nodule is rather modest, though keep in mind that the change...

Hi and welcome to GRACE.  I'm sorry your mom is having this difficulty.  An indwelling catheter is used when the pleura space continually fills and the catheter is always there to...

Hi Oaktowngrrl,  Welcome to Grace.  I'm so sorry you're going through this.

 

 Finding a reputable dedicated thoracic surgeon for lung surgery might be difficult, as it is a complex and...

Recent Comments

JOIN THE CONVERSATION
Could you
By Maeve785 on
It sounds like you’re…
By Dr West on
Thank you Janine
By blaze100 on
Hi Blaze,

 

As much as I…
By JanineT GRACE … on