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Interview with Dr. Suresh Ramalingam on First Line and Maintenance Therapy for Advanced NSCLC
The ASCO meeting I’m at right now is so busy that there really isn’t time to write a new post (though I’m still “tweeting from the meeting”). Though the talk show hows just air re-runs of old shows when they’re on vacation, I’m trying to continue to add new content to the website during this time (and it’s about as far from a vacation as anyone has in Orlando).
Here’s an interview I did with Dr. Suresh Ramalingam, medical oncologist and Director of the Thoracic Oncology Program at Winship Cancer Institute at Emory University. It covers the current status of initial treatment for advanced NSCLC, including controversies and shifting standards for first line and then the transition into maintenance therapy. There’s also an associated slide set (as a pdf file), a transcript, and a link to the audio (mp3) version.
ramalingam-podcast-figures-on-first-line-rx-and-maint2
ramalingam-first-line-and-maintenance-rx-transcript
Ramalingam First Line and Maintenance Rx for Adv NSCLC Audio Podcast
Podcast: Play in new window | Download (0.4KB) | Embed
Interview with Dr. Ramalingam on First Line Advanced NSCLC and Maintenance Therapy
The ASCO meeting I’m at right now is so insanely busy during the days and nights that it’s next to impossible to carve out the time to write posts during the meeting. While the talk show hosts just show re-runs while they’re on vacation, we’re at least going to put up some new content, even if it’s from work previously done (and this is far from a vacation).
This podcast features Dr. Suresh Ramalingam, Director of the Thoracic Oncology Program from Winship Cancer Institute at Emory University in Atlanta. We discussed recent data that have led to changes in our current treatment standards for first line treatment of advanced NSCLC, as well as emerging evidence leading to debates about maintenance therapy after a fixed amount of initial chemotherapy. The video version includes synchronized figures. The audio is an mp3 file.
Ramalingam interview Adv NSCLC and Maintenance Aud
I’ll add the figures and transcript very soon.
Podcast: Play in new window | Download (62.3MB) | Embed
How Helpful are EGFR Inhibitors in Frail, Poor Performance Status Patients with Advanced NSCLC?
Among the many challenges in clinical oncology is the fact that a very significant proportion of our patients are quite a bit more debilitated than the vast majority of patients in clinical trials that test our anti-cancer therapies. Approximately a third of the patients with advanced NSCLC have what would be considered a poor performance status (PS) of 2 or 3 (0 to 5 scale, 0 being asymptomatic, and 5 being dead), but they are extremely under-represented on our clinical trials. Because our anti-cancer therapies, whether standard chemo or targeted therapies, have challenging side effects for many patients, we struggle to balance between fighting the cancer and harming the patient. In the absence of much evidence, we need to rely on our judgment when we make treatment recommendations.
Many physicians and patients have looked upon so-called targeted therapies as a potential alternative to standard chemotherapy drugs that could allow us to treat the cancer more selectively, with less collateral damage to a person’s normal tissues. The oral epidermal growth factor receptor (EGFR) inhibitors like Iressa (gefitinib) and Tarceva (erlotinib) have been the first agents that have been widely used as single agents, and they certainly have activity and can improve survival. Nevertheless, we’ve seen evidence that Tarceva was convincingly inferior to standard chemotherapy for poor performance status patients (at least “unselected” patients who hadn’t been particularly singled out by having an EGFR mutation, being a never-smoker, etc.); another study compared Iressa to the widely used single agent approach of Navelbine in elderly patients (not synonymous with poor performance status) and showed very comparable efficacy. Patients with both good and poor performance status were included in the important clinical trial that showed a survival benefit for Tarceva compared with placebo as a second or third line therapy, dicussed further below.
We get some additional information from a newly reported trial that randomized 201 poor performance status patients (considered to be “unfit for chemotherapy”) to either Iressa or placebo (plus general supportive care for all patients). The study was conducted in several centers in North America and Europe (so very few Asian patients were enrolled, a significant issue because results with EGFR inhibitors are often very different in Asian vs. Western populations). The majority of patients were also older, about half 75 or older, and most of the rest in the 65-74 age range. Importantly, this trial included not only patients with a PS of 2, who are still up and out of bed more than 50% of the time, but also PS 3 patients, who are pretty debilitated and spend more than half of the day in bed (enrollment was an approximately 60/40 split of PS 2 vs. 3 patients). Our experience in studying such frail patients is extremely limited.
Does it Matter Which Chemo Agent You Get with Your Platinum? Maybe it does…
For years it has been generally accepted that the choices for the second drug in a platinum doublet for treating metastatic non-small cell lung cancer (NSCLC) were pretty much interchangeable. The question of whether cisplatin is better than carboplatin is a separate question, one which GRACE’s own Dr. Sanborn recently reviewed quite nicely. For the second drug, as long as the choice was a “newer generation” drug, oncologists would mix and match cisplatin or carboplatin with Taxol (paclitaxel), Taxotere (docetaxel), Gemzar (gemcitabine), or Navelbine (vinorelbine) based mostly upon which drug they liked the best or had the most experience with.
This perception that the specific second drug was irrelevant was not just pulled out of a hat; there has been reason to think they are all equally good. The most often quoted study to make this point has to be the ECOG 1594 trial (Comparison of Four Chemotherapy Regimens for Advanced Non–small-cell lung cancer), which randomized NSCLC patients to one of 4 arms: cisplatin/Taxol, carboplatin/Taxol, cisplatin/Gemzar, and cisplatin/Taxotere. The survival curves were essentially identical (see below), as were the response rates of the tumors.
Video Presentation on Never-Smokers with Lung Cancer
Here’s a video presentation on never-smokers with lung cancer, a population that has been a subject of great interest to me for the past several years. Ten years ago, we really didn’t focus on smoking status as a relevant issue and didn’t break out never-smokers as a group within our lung cancer trials. Over the last few years, and largely on the basis of differences in outcomes that became more clear with the introduction of the EGFR inhibitors, we’re coming to recognize that never-smokers with lung cancer may really represent a distinct disease, with different demographics, pathology subtypes, response to treatments, and overall survival. This video provides a brief overview of the highlights of what we know about never-smokers with lung cancer.
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Cetuximab (Erbitux) for Advanced NSCLC: Promising Results, But is it Ready for Prime Time?
There has been quite a lot of discussion recently about the EGFR tyrosine kinase inhibitors (TKIs), erlotinib (Tarceva) and gefitinib (Iressa). Recently however the final results of the FLEX trial were published in The Lancet, bringing attention back to one of the antibodies against EGFR, cetuximab (Erbitux). Dr. West had previously written about the early presentation of results from this trial in a post after the ASCO meeting last year.
As a background, cetuximab is a monoclonal antibody that is given through the vein weekly. It has been shown to prolong life in combination with chemotherapy for patients with head and neck cancers, as well as for patients with colon cancers. The FLEX (First-Line ErbituX in lung cancer) study was a large randomized trial evaluating whether the combination of cetuximab with chemotherapy would prolong life for patients with NSCLC.
This study enrolled patients with NSCLC whose tumors showed staining by immunohistochemistry (IHC) for EGFR, even if it was only one tumor cell. Patients must have incurable NSCLC and could not have previously received chemotherapy. Of 1688 patients with tumors tested, 1442 demonstrated at least one cell positive for EGFR. 1125 patients were ultimately randomized to receive either six cycles of chemotherapy with cisplatin and vinorelbine (Navelbine) or the same chemotherapy with weekly Erbitux. Patients in the Erbitux arm who didn’t show progression after six cycles then continued to receive it weekly until progressive disease or until they experienced toxicity requiring stopping the drug.
Why “He told me I have a year to live” Makes Me Grit My Teeth: You (the Patient) are Not a Number!
Last Friday I saw a patient in clinic who was referred to me after presenting to the emergency room with shortness of breath. He has a large pleural effusion, and eventually needed a thoracoscopic surgery to drain the effusion and pleurodese the lung (this eliminates the space around the lung so no fluid can collect there).
After his pleural fluid came back positive for NSCLC, the surgeon who did the VATS told him (while still half-asleep in the recovery room, no less) that he “had a year to live, and to get his affairs in order”.
This happens at least once a month, sometimes more, and nothing makes me want to call up some poor ER physician or surgeon and rant at them more than this type of hurtful and misleading comment. OK, deep breath…
Yes, the median overall survival for metastatic non-small cell lung cancer (NSCLC; or extensive small cell lung cancer for that matter) is about a year. But what does that really mean to an individual patient? Some people lay it out as an average: “Well, on average you’ll live about a year.” Aside from being mathematically wrong, who are you, Nostradamus? Unless you can look into a crystal ball, please don’t go around pronouncing life spans.
A Non-Scientific Assessment of Better Lung Cancer Outcomes
This week I happened to see a man in my clinic who I had first met at the time of his diagnosis with metastatic lung cancer more than five years ago. He’s from another part of Washington state, and this was his first time back with me to revisit treatment options. For me it was a time to take a step back and reflect on how well he’s done, with the real question being whether this represented a real change in what we can expect from lung cancer or whether he represents an outlier and that our so-called progress is really modest (as suggested by some of the sobering statistics described in a recent New York Times article). But from the standpoint of an oncologist with a particular interest and expertise in lung cancer, I feel like I’m seeing more lung cancer patients doing better and better than the numbers would indicate.
The gentleman I saw this week is now in his late 50s and is lifelong never-smoker who presented with brain mets (immediately treated with whole brain radiation) and a good amount of disease in his chest. Since meeting me during his initial workup, he’s been managed by a very good community-based general oncologist in a small town in eastern Washington. He was treated with initial platinum-based doublet chemo (old school cisplatin/gemcitabine, actually), then taxotere (docetaxel), and both of these approaches were associated with mild benefit, though nothing spectacular. He started tarceva (erlotinib in early 2005 and had a great response that lasted about three and a half years, then had some new areas of bony metastatic disease. His oncologist actually added alimta (pemetrexed) to his tarceva, an approach I don’t really favor (my take on the evidence is that there may well be an antagonistic effect between EGFR inhibitors and at least some if not most standard chemo approaches used for NSCLC).
Though he’s showing evidence of mild progression again, what’s limiting his activity is degenerative joint pain in his hip and a need for a hip transplant (he had one last year that helped a lot). Otherwise, he’s a genuine cowboy and is planning to literally get back in the saddle after surgery, which I strongly encouraged. And we talked about a bunch of options, but what impressed me most is the thought that we could be revisiting treatment options for him over many years to come. And this from a man who presented with multiple brain metastases over five years ago.
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