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Is Combining Chemo and an Oral EGFR Inhibitor Helpful, Harmful, or Neither?
A central question since the introduction of the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) like Tarceva (erlotinib) and Iressa (gefitinib) has been how best to use them. Specifically, one standard way that we integrate new agents in cancer care is to combine them with the treatment that is our current standard of care. However, four large trials of first line doublet chemo with or without Iressa (the INTACT-1 and INTACT-2 trials) or Tarceva (TALENT and TRIBUTE trials) were both definitively negative. One exception was that the subgroup of never-smokers who received carboplatin/taxol (paclitaxel) with concurrent Tarceva on the TRIBUTE trial actually did significantly better than never-smokers who received chemo alone.
(click on image to enlarge)
However, one important issue with the curves above is that the group receiving Tarceva doesn’t really seem to do better (as indicated by the separation of the curves) until about 6 months into the trial.
And because the chemotherapy portion was limited to six cycles given every three weeks, this means that the recipients of Tarceva didn’t really seem to do better until they had completed chemotherapy and were continuing on Tarceva alone. This, along with some other suggestive bits of inconclusive evidence, led me to be quite disinclined to give an EGFR concurrent with standard chemotherapy, out of concern that they may even be antagonistic with each other. I think a very relevant test would be chemo/Tarceva vs. Tarceva alone in never-smokers, or better yet, people with an EGFR mutation, but the TRIBUTE trial didn’t test was chemo/Tarceva vs. Tarceva alone.
But a trial by the Cancer and Leukemia Group B (CALGB) (Cancer and Leukemia Group A is long gone), known as CALGB 30406, has tried to address this question directly.
Case Discussion with Drs. Blumenschein and Curran: Trying to Interpret Imaging after Chemo/Radiation
Here is the second case in my expert round table discussion on locally advanced NSCLC with medical oncologist Dr. George Blumenschein froMD Anderson Cancer Center and radiation oncologist Dr. Walter Curran from Emory University.
We focus in this case on the decision of which patients with a Pancoast tumor should undergo surgery or a nonsurgical approach of chemo/radiation, the challenge of trying to define the right time to repeat scans after chemo/radiation in locally advanced NSCLC, and we also debate the merits of close observation vs. further interventions in the face of worrisome but still ambiguous imaging findings.
I’ll add that I do find it instructive how varied the advocated treatment approaches are among the various experts when discussing not only this case but so many others I present. These are admittedly challenging cases that don’t fit into any “classic” treatment approach, but these discussions of the range of alternatives offered by experts from so many places speaks to the fact that there is rarely one best strategy.
As always, here is the podcast in both audio and video formats, along with the transcript and figures.
imaging-issues-after-chemoradiation-case-blumenschein-curran-audio-podcast
imaging-issues-after-chemoradiation-case-blumenschein-curran-transcript
imaging-issues-after-chemoradiation-case-blumenschein-curran-figures
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Can Lower Doses of EGFR Inhibitor Therapy Still be Effective?
One nagging question that people often ask about, or at least worry about, is whether they are compromising their ability to benefit from an EGFR tyrosine kinase inhibitor (TKI) like Tarceva (erlotinib) or Iressa (gefitinib) if they need to cut down on the dose because of problems with side effects. Anecdotally, I think just about every clinical oncologist believes that is absolutely not the case, based on the fact that many of our patients who have very dramatic and prolonged responses to EGFR inhibitors have also required one or more dose reductions and continue to do very well on a lower dose than the starting dose of Tarceva at 150 mg/day or Iressa at 250 mg/day. We also know from lab-based work that cancer cells with an EGFR mutation are about ten times as sensitive to the effects of EGFR TKIs than cancer cells without an EGFR mutation. This suggests that patients who have an NSCLC tumor with an EGFR mutation may require a lower than standard dose to still receive the benefits.
At this year’s ASCO meeting, Inoue and colleagues will present a retrospective analysis of outcomes based on dose for patients on their study of standard chemo vs. Iressa for patients with an EGFR mutation detected before starting first line therapy.
(click on image to enlarge)
ASCO Preview on TORCH Trial: Treatment Order Matters
Despite the fact that many of the most anticipated ASCO abstracts are still being withheld until the meeting itself, there is certainly a lot of information in the released abstracts that provide a tantalizing preview and already hint at some important new conclusions. I’ll try to provide some ongoing thoughts leading into the meeting coming up in two weeks.
The first I want to highlight is the TORCH trial, an international study being presented by Italian lung cancer leader Cesar Gridelli. This study looks at the question of whether the order of therapy matters: patients in this phase III study were randomized to cisplatin/gemcitabine as first line therapy, followed by the EGFR inhibitor Tarceva (erlotinib) on progression, or the reverse of first line Tarceva followed by cisplatin/gemcitabine at progression. A total of 760 patients, not selected for particular histology (55.5% hadadenocarcinomas), smoking status (20.6% never-smokers), race (3.2% East Asian), or EGFR mutation status (not tested), were enrolled. This is in a population that we must presume is likely to have only a small minority of patients as EGFR mutation positive.
The results demonstrate that the order of therapy matter and that there are consequences of giving the less optimal treatment first. Specifically, at the time of a planned interim analysis of the ongoing results, the differences in survival were striking enough, 40% worse for those who started with Tarceva, that the trial was closed for further enrollment. The difference in median overall survival is 10.8 months vs. 7.7 months, favoring initial chemotherapy: a statistically and clinically significant difference, to be sure.
Case Discussion on Stage IIIA N2 NSCLC, with Drs. Blumenschein & Curran
Several weeks ago I had the opportunity to discuss a series of cases of locally advanced NSCLC with a couple of expert colleagues: Dr. George Blumenschein, medical oncologist in the Division of Thoracic & Head/Neck Oncology at MD Anderson Cancer Center in Houston, TX; and Dr. Walter Curran, radiation oncologist who heads the Division of Radiation Oncology at the Winship Cancer Center at Emory University in Atlanta, GA. Dr. Curran is also the head of the Radiation Therapy Oncology Group, the US-based cooperative oncology group leading important questions about radiation oncology in various cancer types.
The first of the cases we covered is a patient of mine with stage IIIA N2 NSCLC, the most controversial setting in lung cancer management, where many options are all considered as reasonable alternatives throughout the oncology field.
Here’s the audio and video versions of the podcast, along with the transcript and figures.
stage-iiia-n2-nsclc-case-drs-blumenschein-and-curran-audio-podcast
stage-iiia-n2-nsclc-case-drs-blumenschein-and-curran-transcript
stage-iiia-n2-nsclc-case-drs-blumenschein-and-curran-figs
Podcast: Play in new window | Download (47.1MB) | Embed
Systemic Therapy for Patients with Early-Stage Non–Small-Cell Lung Cancer
Introduction to Adjuvant Therapy: Why More than Just Surgery?
For patients with early-stage non-small-cell lung cancer (NSCLC) (stages I, II and some III), surgical resection (removal by surgery) is the standard treatment. Unfortunately, the rates of recurrence (cancer returning) after resection can be high, and additional therapy (chemotherapy) can improve the odds that the cancer won’t return for some patients. This article goes through the data we have that demonstrate the benefit of chemotherapy after surgery for early stage lung cancer, information about chemotherapy before surgery, new treatments being studied for lung cancer patients after surgery and ongoing studies to help better determine which patients might benefit the most from particular treatments. We have learned about the importance of chemotherapy and other treatment after surgery from patients who were willing to go on clinical trials. Patients on the trials either received new treatments or were randomized (assigned by chance) to either get chemotherapy or not after surgery. The information below comes from the analyses that have been done of the patients who were willing to participate in clinical trials.
Advanced NSCLC in the Frail/Elderly: Podcast of Discussion with Drs. Hesketh and Kelly
The last of our three cases reviewing management issues in elderly and frail patients with lung cancer, as covered in a recent webinar discussion I had with experts Paul J. Hesketh from Lahey Clinic and Karen Kelly from Kansas University Medical Center, focuses on treatment of advanced/metastatic NSCLC. Drs. Hesketh and Kelly are two of the world experts in this field that so desperately needs more research and careful thought, given that the median age of patients newly diagnosed with lung cancer in the US is now just over 70, and about a third of patients are frail, but our studies primarily or exclusively include younger, healthy patients. In fact, the figures include the reference of a review article that Dr. Hesketh is just publishing now in the Journal of Thoracic Oncology on treating patients 80 and older with lung cancer (it appears online but hasn’t appeared in the actual printed journal yet).
Here is the audio and video versions of the podcast, along with the figures and transcript.
adv-nsclc-in-frail-and-elderly-patients-hesketh-and-kelly-audio-podcast
adv-nsclc-in-frail-and-elderly-patients-hesketh-and-kelly-transcript
adv-nsclc-in-frail-and-elderly-patients-hesketh-and-kelly-figs
Podcast: Play in new window | Download (39.4MB) | Embed
General Work-up and Staging of Lung Cancer: What Do You Need to Know?
The medical literature tells us that one of the most stressful times of a patients’ cancer course is the time between discovering that they may have cancer and beginning their treatment. So much is new and unknown. For many patients, this is their first exposure to the health care system. The patient often requires multiple tests and need to consult with different physician specialties, sometimes in different hospitals before treatment can begin.
It can be a time where well meaning family and friends provide advice and anecdotes from their experiences with cancer. Such advice can be helpful but sometimes can lead to further confusion. Add to that the explosion of information on the internet with the gravity of finding out you may have cancer, and it is no wonder that patients find themselves scared, anxious, and confused.
To help organize and simplify the process leading up to the treatment of the patients disease, it may be good to think in terms of a 3 step pathway; diagnosis (what is it?), stage (where is it?), and treatment options (what can I do about it?). Each of these steps is critically important, because the treatment options you will be provided with vary considerably by the type and location of lung cancer and the general health of the patient. If the diagnosis and stage are not adequate, the patient may receive the wrong treatment, and that could adversely effect survival. Continue reading
Locally Advanced NSCLC in the Frail/Elderly: Podcast of Case Discussion with Drs. Hesketh and Kelly
Here is the second of three cases covering issues in managing elderly and frail patients with lung cancer that I discussed with experts Paul J. Hesketh from Lahey Clinic and Karen Kelly from Kansas University Medical Center. Both major experts in lung cancer, they have a lot of experience and have been leaders in publishing on the understudied population of elderly and poor performance status patients with lung cancer. This particular case covers treatment options for a patient with unresectable stage III non-small cell lung cancer (NSCLC).
Here is the audio and video versions of the podcast, along with the figures and transcript.
loc-adv-nsclc-in-frail-and-elderly-patients-hesketh-and-kelly-audio-podcast
loc-adv-nsclc-in-frail-and-elderly-patients-hesketh-and-kelly-transcript
loc-adv-nsclc-in-frail-and-elderly-patients-hesketh-and-kelly-figures
Podcast: Play in new window | Download (0.0KB) | Embed
Adjuvant Therapy in the Elderly and/or Frail: Podcast of Discussion with Drs. Hesketh and Kelly
Several weeks ago I had the opportunity to discuss several difficult cases with experts Drs. Paul Hesketh from the Lahey Clinic outside of Boston and Karen Kelly from Kansas University Medical Center in Kansas City, KS. These scenarios raise questions about how best to manage lung cancer issues in elderly and/or frail patients, starting with a 78 year-old woman who presented to me for discussion of the pros and cons of post-operative therapy, which also touch on other factors of administering chemotherapy to more marginal patients in general, regardless of the setting.
Here are the audio and video versions of the podcast, along with the transcript and figures.
adjuvant-therapy-in-frail-and-elderly-patients-hesketh-and-kelly-audio-podcast
adjuvant-therapy-in-frail-and-elderly-patients-hesketh-and-kelly-transcript
adjuvant-therapy-in-frail-and-elderly-patients-hesketh-and-kelly-figures
Podcast: Play in new window | Download (74.9MB) | Embed
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