Archive for the ‘Ask the Experts’ Category

Dr. Jack West

Nuances in Which Patients Should Receive Adjuvant Chemotherapy for Node-Negative Resected NSCLC

May 11th, 2012 - by Dr. Jack West

Last weekend, I participated in a debate on the question of whether people who had undergone a resection of a node-negative early stage non-small cell lung cancer (NSCLC) should ever be candidates for adjuvant (post-operative) chemotherapy.  I had been assigned the side of there being a role for adjuvant therapy “sometimes”, as opposed to “never”.  Besides the truism that always and never are very rarely the right answer in medicine (can’t say these are never the right answer), I also had been assigned an easier task because I would say that the evidence does favor the concept that there aren’t ironclad rules about which patients are better served by pursuing adjuvant chemotherapy and which ones may well do better without it.

The basic principle is this: we know that people who undergo surgery for lung cancer remain at some risk for the cancer recurring.  The stage of the cancer provides a pretty good approximation of the prognosis, which is really primarily the likelihood of the cancer recurring and the patient dying from the cancer.  The lower the stage (from Ia on the low end to IVb on the high end), the better the prognosis.  In the world of resectable, curable NSCLC, patients who have stage II or IIIa NSCLC are the group of surgery patients who have the strongest evidence to support additional therapy after surgery, and the results are much more equivocal for patients with stage Ib NSCLC (in the slightly outdated staging system that was used in these trials, these were primarily people with a cancer larger than 3 cm or with a smaller one but pleural lining involved by tumor, and no lymph nodes involved).

Chemotherapy, typically 3-4 cycles of a platinum-based doublet combination, has been shown to reduce the risk of the cancer recurring, thereby improving survival, in higher risk patients.  How much of a benefit it provides depends on how great the risk is that the cancer will recur: it is relative to the risk of recurrence.  What this means is that for people with a very high risk of recurrence, like 50-75% with surgery alone, that reduction in absolute terms may be pretty substantial, in the range of a 20% reduction.  In contrast, if a person has a very low risk of recurrence, such as 10% for a very small and well-behaved cancer, the absolute reduction might be more like 1-2%.  In contrast, the detrimental effect of chemotherapy, in terms of both acute challenges and potential long-term risks, are the same whether someone has a more threatening or a less threatening cancer.  The detrimental effects are more related to the health of the patient.

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Dr. Jack West

Panel Discussions on Molecular Markers in Advanced Lung Cancer: Check them out!

May 4th, 2012 - by Dr. Jack West

Here are a couple of additional installments from our special two hour webinar on molecular markers in advanced NSCLC, broadcast from the Santa Monica Targeted Therapies in Lung Cancer conference and featuring four great panelists who joined me that day:

  • Drs. Charlie Rudin, Johns Hopkins University
  • Dr. Alice Shaw, Massachusetts General Hospital
  • Dr. David Spigel, Sarah Cannon Cancer Center
  • Dr. Glen Goss, University of Ottawa, and head of NCI-Canada’s Lung Cancer Committee

Part three of our program includes some debate on the merits of uniform vs. more selective testing of “druggable” targets, as well as a discussion of whether to favor simultaneous testing for molecular targets vs. a sequential, stepwise approach (because the key relevant targets are mutually exclusive).  We also review the challenge of delays in treatment that can emerge as a byproduct of weeks of up front testing.

Below you’ll find the audio and video versions of the podcast, along with the transcript and figures for this activity.

Molecular Targets PD Pt 3 Video Podcast

Molecular Targets PD Pt 3 Audio Podcast

Molecular Targets PD Pt 3 Transcript

Molecular Targets PD Pt 3 Figures

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Dr. Jack West

Doubts Raised About Avastin’s Benefit in Older Patients with Advanced NSCLC

April 27th, 2012 - by Dr. Jack West

In a very recent publication in the Journal of the American Medical Association (JAMA), a group from Dana Farber Cancer Institute in Boston reported that the targeted anti-angiogenic agent Avastin (bevacizumab) may provide no meaningful benefit when added to chemotherapy in older patients with advanced non-small cell lung cancer.  To provide some review on this controversial topic, Avastin was studied in a randomized phase III study called the ECOG 4599 trial and found to lead to a survival benefit when it was added to carbo/Taxol in Avastin-eligible patients.  This group of “Avastin-eligible” was a limited subset generally defined by a good performance status (active, generally healthy), no brain metastases (an initial requirement that has been relaxed with more experience showing no markedly increased risk of bleeding in the brain in patients with treated, asymptomatic brain metastases), no significant hemoptysis (coughing up blood), and non-squamous NSCLC histology — the latter two being exceluded because of an identified high risk of life threatening or fatal hemoptysis in patients with squamous NSCLC or a history of coughing up more than a very scant amount of blood.  

The positive trial led to the approval of Avastin by the US FDA in late 2006 for addition to carbo/Taxol in advanced NSCLC for the eligible subset of patients, but there have always been nagging questions as to how much benefit it really offers, particularly in older patients.  A post-hoc subset analysis of the ECOG 4599 trial indicated that patients 70 and older who received Avastin derived no survival benefi, likely because they experienced disproportionately greater side effects than younger patients from the addition of Avastin.   Meanwhile, another randomized phase III trial done in Europe with a different chemotherapy backbone, called AVAiL (AVAstin in Lung cancer), demonstrated a relatively unimpressive though statistically significant improvement in response rate and progression-free survival when Avastin was added to cisplatin and gemcitabine, but AVAiL showed no benefit  in overall survival.  

Following its FDA approval, Avastin has been recognized in the oncology community as a standard of care, but not unquestionably the standard of care; in fact, only about 20-25% of patients in real world cancer care in the US actually get it.  The reason it is incorporated for only a minority of patients remains debatable and is likely due to several factors. I think that when there are many well-established exclusion factors, and then you need to factor in several “relative contraindications” — for example, cancer growing near blood vessels that could pose a higher bleeding risk, or a poorly differentiated cancer that is suspected may be of squamous histology — the actual proportion of patients who remain good candidates for Avastin could well be less than 40%.  Beyond the question of eligibility, there is also the issue of whether the positive results of the ECOG trial definitely outweigh the absence of survival the AVAiL trial and the absence of a survival benefit in older patients on the ECOG trial.  It’s also important to remember that the median age of newly diagnosed lung cancer in the US is ~71, meaning that more than half of patients with advanced NSCLC are in an age range where the value of Avastin is particularly questionable.

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Dr. Jack West

Initial Presentations from Santa Monica Targeted Therapies Discussion: Drs. Rudin and Shaw

April 20th, 2012 - by Dr. Jack West

Here is the introduction and first two presentations from our special webinar at the Santa Monica “Targeted Therapies in Lung Cancer” meeting several weeks ago. I was honored to be joined there by four guest faculty members who are true experts in the field — Dr. Charles Rudin from Johns Hopkins University in Baltimore, Dr. Alice Shaw from Massachusetts General Hospital in Boston, Dr. David Spigel from Sarah Cannon Cancer Center in Nashville, and Dr. Glen Goss from the University of Ottawa. We discussed the complexity of this evolving field and where our perspectives converge and differ.

Immediately below are the audio and video versions of the first podcast, with introductory comments and then a presentation by Dr. Rudin on the Lung Cancer Mutation Consortium. You’ll also find links to the transcript and figures.

SM Molecular Markers Pt 1 Intro and Rudin on LCMC Video Podcast

SM Molecular Markers Pt 1 Intro and Rudin on LCMC Audio Podcast

SM Molecular Markers Pt 1 Intro and Rudin on LCMC Transcript

SM Molecular Markers Pt 1 Intro and Rudin on LCMC Figures

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