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New Data on Continuation Maintenance Therapy for Advanced NSCLC
A lot of new data have emerged over the last 2-3 years that have addressed the concept of “maintenance therapy” for patients with advanced NSCLC (see Dr. Socinski’s excellent podcast for a general review). The basic idea is that a patient is treated with first line chemo-based treatment, with or without the angiogenesis in inhibitor Avastin (bevacizumab), and the fortunate majority have some degree of tumor shrinkage or at least stable disease. The degree of benefit from each subsequent cycle of chemotherapy tends to decrease with further treatments, so you reach a point of diminishing returns for an often-challenging two or three-drug combination. While the well-established standard up until a few years ago had been to stop first line therapy and observe a patient for progression before initiating second line treatment, several trials in the last few years have demonstrated that lighter ongoing maintenance therapy, more to suppress the cancer at its current state of prior response and non-progression than to markedly shrink the cancer further, provides a very significant improvement in progression-free survival, and a less clear but at least strongly suggested overall survival benefit (the trials showing a significant improvement in overall survival have some substantial flaws).
There are two basic concepts of maintenance therapy: one is switch maintenance therapy, in which someone stops all of the first line drugs and switches to a new therapy to maintain the response. It has the theoretical advantage of treating the cancer from a new angle, with an agent that the remaining cancer has not had the opportunity to develop resistance to. The approvals of both Alimta (pemetrexed) and Tarceva (erlotinib) as maintenance therapies are based on this concept. In contrast, continuation maintenance therapy is when one or more of the agents from the first line setting is continued after a fixed number of cycles of first line therapy. We haven’t had much data on this concept with modern chemo approaches, but this year at ASCO, a couple of interesting trials were presented that provided some additional insight on this approach (though oncologists often use this approach with Avastin and Alimta, we haven’t seen data that demonstrate continuation maintenance with these agents is beneficial).
Update on ATLAS: Overall survival
We learned several months ago that the ATLAS trial of maintenance Avastin (bevacizumab) with either Tarceva (erlotinib) or placebo did not demonstrate a significant improvement in overall survival (OS) with Tarceva, despite the fact that it was associated with an improvement in progression-free survival (PFS). This is in contrast with the similar trial called SATURN that randomized advanced NSCLC patients after first line chemo to maintenance Tarceva vs. placebo, but without the Avastin during and after first line chemo, as SATURN demonstrated a significant improvement in OS along with a significant improvement in PFS.
In Dr. Mark Socinski’s great overview of the topic of maintenance therapy, he noted these discrepant results, with no obvious explanation. We received additional information about the OS results at ASCO, where it was reported that at the latest time point of analysis, in July of 2009, the median OS was 15.9 months vs. 13.9 months, favoring the addition of Tarceva. This corresponded with a hazard ratio of 0.90, or 10% improvement, over the entire course of treatment, a result that was not statistically significant. The overall survival curves are shown below:
(click on image to enlarge)
Admittedly, it doesn’t look like a major separation, but there is a modest advantage with the combination. You can decide whether that’s a glass half empty or half full.
Case Discussion with Dr. Hanna: Asian Never-Smoking Woman with Stage IIIA N2 NSCLC
Here is the continuation of my conversation with Dr. Nasser Hanna, lung cancer expert at Indiana University and all-around good guy (not part of his official title). Here we discuss a patient of mine who combines the challenges of managing stage IIIA N2 NSCLC with the issues of how to potentially integrate an EGFR inhibitor for an Asian never-smoker, particularly in a setting where we don’t yet have good data.
At the tail end of the case, we also take a bit of a detour in discussing the question of whether the order of therapy matters as much as getting in the right therapies over time, specifically with regard to trying to prioritize chemo vs. an EGFR inhibitor.
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Dr. West: This case is of a 54 year old lifelong never smoking Asian woman who was involved in a motor vehicle accident and went to the emergency room and she had a chest x-ray there followed immediately by a CT of the neck and chest. She had a 2.4 centimeter right upper lobe spiculated mass and she also had several lucencies in her C2 verterbral body, very non-specific appearing. She had musculokeletal injuries in her sternum and actually a pelvic fracture.
She subsequently had a PET scan that showed the right upper lobe mass had an SUV of 4.5. Other findings were consistent with trauma, nothing suggestive of hiler or mediastinal uptake, nor any distant disease.
Case Discussion on Adjuvant Therapy for Stage IB NSCLC with Dr. Nasser Hanna
It’s been a few months since I sat down with my friend, Dr. Nasser Hanna, a great lung cancer expert from Indiana University, and also a friend in the field. Those of you who have been following GRACE content for a while may have come across his name: he’s led a few of the more important trials that are part of our current core knowledge in lung cancer now, such as the trial that directly compared Alimta (pemetrexed) to Taxotere (docetaxel) as second line therapy for advanced NSCLC; the Hoosier Oncology Group (HOG) trial that showed no benefit to consolidation Taxotere after chemo/radiation for stage III NSCLC; a trial of maintenance therapy with oral etoposide after initial cisplatin/etoposide for extensive stage small cell lung cancer, as well as others.
Here’s a transcript and a few key images from our discussion of a challenging case of an elderly woman considering the merits of post-operative chemotherapy for stage IB NSCLC. (I’ll just note that this format of presenting a transcript and a few figures is a fast, cheaper way for us to present the content of conversations we’ve been turning into podcasts until this point. It may be easier to just have it here online, and cuts our costs. If you have a definite preference for the audio/visual format of a podcast vs. this, please voice that opinion).
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Dr. West: Hi, I’m Jack West, Medical Oncologist and President of GRACE, The Global Resource for Advancing Cancer Education. I’m here today with Dr. Nasser Hanna who is Associate Professor in the Department of Medicine, a Medical Oncologist at Indiana University and he was good enough to sit with me and talk about a few complex cases, so thanks for taking the time.
Dr. Hanna: Thanks for having me.
Dr. West: Let’s start with a challenging type of situation that isn’t rare in the adjuvant setting. I saw a 73 year old woman…use to smoke up to a couple of packs per day for fifty years and brought her self down to a few cigarettes per day. She has a good performance status and several months ago developed a worse cough, productive of some clear sputum, no hemoptysis and she was prescribed antibiotics but didn’t get better.
Positive trial for Abraxane in NSCLC: Follow-up From ASCO
Three months ago, I discussed the press release from Abraxis reporting that the phase III trial of carbo/Abraxane (nanoparticle albumin-bound paclitaxel) vs. carbo/taxol (paclitaxel) showed a significant benefit for higher response rate in the Abraxane arm. Carboplatin was given one day every three weeks, as was taxol, and Abraxane was given every week (no break). We received more information, though not a lot more, with the presentation at ASCO earlier this month.
The trial enrolled 1053 patients with previously untreated advanced NSCLC, the majority from Russia and the Ukraine, to either standard carbo/taxol or the albumen-bound form that doesn’t require steroid pretreatment and has a somewhat different toxicity profile. We don’t have progression-free survival (PFS) or overall survival (OS) data yet, but we did get some numbers for response rates. Specifically, according to a pre-planned independent radiologist review, the carbo/Abraxane arm had a RR of 33%, compared with 25% for carbo/taxol. The numbers were a little higher in the investigator-reported numbers, but with essentially the same difference (37% vs. 30%).
(click on image to enlarge)
Round Table with Drs. Blumenschein and Curran, Bulky Stage IIIB NSCLC
Here is the third and final case I discussed with two great experts in locally advanced NSCLC. Drs. George Blumenschein, medical oncologist from MD Anderson Cancer Center in Houston, and Wally Curran, radiation oncologist from Winship Cancer Center at Emory University in Atlanta, joined me several weeks ago to discuss a series of challenging cases that illustrate the complexities and array of options in treating patients with stage III NSCLC.
This case is a woman with bulky stage IIIB NSCLC that involves lymph nodes above the collarbone (supraclavicular lymph nodes) on both sides, putting her in the outer reaches of what we could envision being treated for cure. Our discussion includes consideration of the potential approaches, including the potential value of chemo before or after concurrent chemo and radiation. It also covers the difficulty of assessing response after treatment, and the risk of radiation pneumonitis.
case-round-table-bulky-stage-iiib-nsclc-drs-blumenschein-and-curran-audio-podcast
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case-round-table-bulky-stage-iiib-nsclc-drs-blumenschein-and-curran-transcript
Podcast: Play in new window | Download (0.0KB) | Embed
All the Talk About ALK, and Crizotinib (PF-02341066)
Probably the leading story in lung cancer at ASCO this year was about ALK inhibitor therapy and the Pfizer drug crizotinib (PF-02341066). Though we’ve covered it before, last year the promising story remained under the radar for a while after having the initial work presented in a session on developmental therapeutics. This year was the official coming out party for crizotinib, with the phase II study previously described in prior work re-presented with additional patients, but now in the most visible forum in the oncology world.
In fact, you could certainly hear some grumbling about whether this work merited being part of the ASCO Plenary Session, being a phase II study that is applicable to only a small minority of patients with an ALK rearrangement (about 4-5% of NSCLC overall, though disproportionately never-smokers and those with an adenocarcinoma, and especially younger patients) and a story that had already been broken. However, this information was largely known primarily to the lung cancer community and well-informed members of the patient/caregiver communities (especially GRACE participants). It hasn’t really penetrated throughout the oncology community.
Comprehensive Review of Mesothelioma
What is mesothelioma?
Mesothelioma is a unique cancer that starts from the mesothelium, the membrane lining that contains the body cavities. Mesothelioma can arise from the pleura (lining of the lungs), pericardium (sac around the heart), peritoneum (abdominal lining), and tunica vaginalis testis (lining of the male reproductive organs). The majority of mesothelioma cases originate from the pleura.
Epidemiology and Cause of Mesothelioma
Mesothelioma occurs everywhere in the world. In the United States, it is estimated that ~3000 new cases of mesothelioma occur each year. Western Europe has over 5000 new cases/year and China estimates 4000 new cases/year.
The main cause of mesothelioma is environmental and well-established; patients have often been exposed to asbestos fibers in their work or living area. Asbestos is a long thin silicate mineral and has been linked not only to mesothelioma but also to pneumoconiosis and lung cancer. Asbestos was a popular material used in insulation and construction because it had desirable properties of heat/fire and chemical resistance. The fibers are hazardous when they become airborne and are inhaled or swallowed. There are 2 main classes of asbestos: serpentine and amphibole. Serpentine minerals (chrysotile) account for 95% of the asbestos in buildings in the United States. The amphibole group consists of 5 types of asbestos – amosite, crocidolite, anthophyllite, tremolite, and actinolite. Amosite is called the brown asbestos and is found in building materials. The types of asbestos that are most carcinogenic are amosite and crocidolite. However, chrysolite also is hazardous and is linked to development of mesothelioma in people.
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