GRACE :: Lung Cancer
Dr West

Dr West


Dr. West attended Princeton University before heading to the University of Cambridge on a Fulbright Scholarship. He then returned to the US to attend Harvard Medical School, where he was honored as a Howard Hughes Medical Institute Research Fellow. He did his internship and residency training at Brigham & Women’s Hospital in Boston before moving to Seattle for his specialty training at the Fred Hutchinson Cancer Research Center/University of Washington, where he served on faculty after completing his fellowship in medical oncology. Since that time, he has fused his commitment to patient care at Swedish Cancer Institute in Seattle, focusing on thoracic and genitourinary oncology with a commitment to clinical research as well as entrepreneurial ventures. While overseeing a cancer clinic that draws patients from all over the world, he offers a wide array of clinical trials and leads several, including serving as Principal Investigator of several phase II national trials with the Southwest Oncology Group. He has emerged as a very rare oncologist based in a private practice setting yet remains a nationally to internationally recognized expert, thought leader, speaker and writer. Dr. West has also pioneered many new ventures that exercise his interests in social media, new educational platforms, and even marketing. He founded Go West Health Care Consulting in 2004, which has flourished into a very successful company that enabled him to pursue roles in developing of a wide range of oncology products, lead dozens of pharmaceutical advisory boards, speak and write for professional and patient oriented audiences, help in developing educational and marketing materials, serve as a medical director for a CME company, and even work as the dedicated oncology consultant to a large marketing agency. He is widely recognized as an oncologist who understands the complex market forces from scientific background to commercial development strategies to current and future practical market forces within the oncology space – the only oncologist who has delivered a TEDx presentation and attends not only ASCO but TEDMED, South by SouthWest interactive, and the American Telemedicine Association’s annual conference. Finally, recognizing that patients and caregivers are a remarkably underutilized resource and critical voice in medical decision-making, Dr. West developed OncTalk.com in 2006 as a mechanism to provide very timely, specialized free information about cancer directly to a global patient community. This effort transitioned to become the nonprofit Global Resource for Advancing Cancer Education (GRACE) (www.cancerGRACE.org) in 2007, which has continued to grow rapidly, now integrating participation from many expert physicians and other health care specialists and reaching tens of thousands of people in over 130 countries each month. His efforts have provided expert content in a wide range of formats, including blog posts, audio and video podcasts, and an interactive discussion forum that have led to his being recognized as an international leader in the growing role of the educated patient as a means of shaping medical care and ultimately improving patient outcomes. “You are truly a Godsend -- I am thankful for the support and compassion you offer people throughout the world. I appreciate it more than words can convey.” —GRACE Member Linda P.
Dr West

Why I Don’t Favor an Front-Loaded Approach for Most Advanced NSCLC Patients

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To many, the recent FDA approval of a combination of chemotherapy and concurrent immunotherapy for the vast majority of patients with advanced (metastatic) non-squamous non-small cell lung cancer (NSCLC) probably seems like a great idea. This approval was based on the more favorable results for the combination of the IV immunotherapy agent Keytruda (pembrolizumab) every 3 weeks along with first line carboplatin and Alimta (pemetrexed) as a the chemo backbone, compared to the same chemotherapy alone, in a relatively small randomized trial of 123 patients, called KEYNOTE-021g. The “g” part refers to this actually being just one portion of a much larger trial comparing chemo to the same chemo with Keytruda. The other arms haven’t panned out as favorably.

Importantly, when we talk about the arm of patients getting chemo combined with immunotherapy, we aren’t talking about improving survival. Instead, we’re talking about prolonging the time before patients showed significant progression of their cancer on scans, which leads us to switch to a new treatment. This “progression-free survival”, or PFS, was the primary goal of the trial, though the gold standard of what we should really want from our treatments is improvement in how long patients live. There’s a bit of a favorable trend for that, but that’s all. There was also a significant improvement in the fraction of patients who show major shrinkage of their cancer when Keytruda is added to chemotherapy.

Still, even if survival isn’t improved, the results seem promising enough, so what’s not to like? Continue reading


Dr West

My Top 10 ASCO 2017 Lung Cancer Presentations

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Over the next few days, about 30,000 oncologists and other cancer care professionals, along with a growing number of patient advocates, are converging on Chicago for the American Society for Clinical Oncology (ASCO) annual conference, the biggest cancer meeting of the year. There is far too much happening for people to be able to see everything, but fortunately people will be providing summaries on Twitter (follow me at @JackWestMD), various blogs (I’m writing commentary for Medscape), and lots of online and print news outlets.  GRACE will be doing an annual “highlights” video series in just a few weeks, but in the meantime, here is a preview of the top 10 presentations in lung cancer from my perspective, primarily thinking about likely impact on clinical practice for thoracic oncology patients:

JW Top 10 LC presentations for ASCOJW Top 10 LC presentations for ASCO pt 2


Dr West

New FDA Approval for Zykadia (ceritinib) for ALK-Positive NSCLC: Why I Think It’s a Poor Choice for Initial Treatment

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The FDA just approved a new therapy for the approximately 4% of patients with NSCLC who have the molecular marker known as an ALK rearrangement. The agent Zykadia (ceritinib), a “second generation” ALK inhibitor that is more effective than Xalkori (crizotinib) in lab models of ALK-positive NSCLC, and the new approval was for Zykadia as first line treatment for ALK-positive lung cancer, a setting where we have historically favored Xalkori since it was approved in 2011. . Despite the FDA approval for ceritinib, I don’t believe it should be favored as a first line therapy for ALK-positive patients. Why would I not favor it?

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Dr West

Imprecision Medicine: Why Keytruda (Pembrolizumab) + Chemo for PD-L1+ NSCLC isn’t Ready for Prime Time

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Let me start by saying that I’m a fan of the immune checkpoint inhibitor Keytruda (pembrolizumab) and consider it the new standard of care as a single agent (monotherapy) first line treatment for the subset of about 28-30% of patients with advanced NSCLC, either squamous or non-squamous, whose cancers have high level expression of PD-L1, defined as 50% or more cancer cells staining on the companion test for Keytruda (an antibody called 22c3).  It can lead to some terrific and long-lasting responses, but it works well only in a minority of patients; in fact, even in the cherry-picked population of patients with cancers that show high PD-L1 expression, the response rate is a little less than 50%, and it’s below 20% in patients with low or no PD-L1 expression. Merck just announced that the FDA has accepted a “supplemental Biologics License Application” (sBLA) that would broaden the FDA approval for Keytruda in NSCLC to all non-squamous NSCLC patients without an EGFR mutation or ALK rearrangement and without regard to PD-L1 expression, giving Keytruda in combination with chemotherapy (carboplatin and Alimta (pemetrexed)).  I think the evidence we have with this combination is encouraging and worthy of further study, but it shouldn’t be enough to lead to broad use as requested in the FDA filing. I think it’s a premature money grab that isn’t necessarily better for patients and is definitely bad for broad society. Let me explain why.

The evidence behind this strategy is from a cohort of patients (cohort G) from a larger study, KEYNOTE-021) of patients randomized to various chemo combinations with or without Keytruda. This particular trial did not have a threshold requirement for PD-L1 and enrolled 123 patients with a good performance status and advanced NSCLC to receive either carboplatin/Alimta alone or the same chemo with Keytruda at a fixed dose of 200 mg IV every 3 weeks. Patients who hadn’t progressed after 4 cycles would continue to receive maintenance Alimta (for the chemo only arm) or Alimta/Keytruda (for the chemo/immunotherapy arm) until progression or prohibitive side effects.

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Dr West

First Line Immunotherapy for Advanced Non-Small Cell Lung Cancer: A Great Option for Some, but Not for All

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General-Campaign-Logo-300x300Several weeks ago, at a very crowded plenary session for the European Society of Medical Oncology (ESMO) in Copenhagen, Denmark, results with first line immunotherapy compared to standard first line chemotherapy for patients with advanced non-small cell lung cancer (NSCLC) were presented that simultaneously ushered in a new era for testing for PD-L1, the leading predictive marker for sensitivity to immunotherapy, and indicated both the new promise and limitations of PD-1 immune checkpoint inhibitors such as Keytruda (pembrolizumab) and Opdivo (nivolumab). In fact, the remarkably different results from two similarly designed trials leave us in a new world, but also one in which further change is coming.

First, let’s discuss the positive results for first line. The KEYNOTE-024 trial, which enrolled 305 patients with high level expression of the PD-L1 antibody marker known as 22C3 (>50% of tumor cells staining positive, seen in about 30% of patients with advanced NSCLC overall), randomized patients to either first line treatment with standard chemotherapy with any of several chemotherapy doublets or Keytruda at a new fixed dose of 200 mg IV every 3 weeks. Notably, patients with an EGFR mutation or ALK rearrangement were excluded from the trial, based on evidence that these patients are far more likely to benefit from the targeted therapies against their driver mutations than either chemotherapy or immunotherapy. Patients assigned to Keytruda were to continue until significant side effects or progression. Patients who were assigned to chemotherapy could receive maintenance Alimta (pemetrexed) if they had not demonstrated progression after 4-6 cycles of initial doublet chemotherapy; patients on the chemotherapy arm were eligible to cross over to receive Keytruda as second line therapy. 

The trial demonstrated a highly significant improvement in progression-free survival (PFS); the median PFS (the time when half of patients have progressed and half have not) being 10.3 months for the first line Keytruda recipients vs. 6.0 months for the first line chemo patients. The differences became more pronounced with longer follow up, so that by 1 year from the start of treatment, 48% of patients assigned to Keytruda still hadn’t progressed, while 15% of the patients starting on chemo hadn’t progressed. In terms of response rate, the probability that measurable cancer will shrink significantly, it was significantly better with Keytruda – 45% vs. 28%.  As is typical with immunotherapy trials, chemotherapy caused more side effects, though a minority of patients will have challenging and even rarely serious side effects with immunotherapy.

Both groups of patients did relatively well in terms of overall survival (OS), but a higher proportion of those starting with Keytruda remained alive a year into the trial (70% vs. 54%). Based on these differences in efficacy favoring Keytruda, the Data Safety Monitoring Committee following the trial recommended stopping the trial because it would have been considered unethical to continue to randomize patients to chemotherapy in light of the emerging findings. Notably, however, while this survival benefit was seen despite the built-in crossover of chemo patients to Keytruda, only about half of the progressing patients had received immunotherapy, a low proportion that is unexplained, disappointing, and partly challenges the idea that it is critical to get immunotherapy first, because too many patients assigned to first line chemo failed to ever get immunotherapy, despite the fact that this is a treatment that has been repeatedly proven to improve survival as a second line therapy.

With that presentation and the simultaneously published article in the New England Journal of Medicine, the standard of care for advanced NSCLC changed, as indicated by the remarkably quick update in the NCCN guidelines (the leading treatment recommendations put forth by a group of cancer experts as defining our best treatment) and a new approval for Keytruda as first line therapy, specifically for patients with high level expression of PD-L1. This means that it is now necessary to have the tumors of newly diagnosed patients with advanced squamous or nonsquamous NSCLC tested for PD-L1, and for the 30% of patients with high level expression of PD-L1, to favor single agent Keytruda.

But despite this clear victory for immunotherapy in advanced NSCLC, this doesn’t mean that most or all patients should get immunotherapy as initial treatment. Though some provocative data came out looking at chemo combined with immunotherapy as first line therapy, that relatively small trial didn’t show a survival benefit compared with first line chemo followed by immunotherapy. We need to also remember that the trial excluded patients with an EGFR mutation or ALK rearrangement, as the oral targeted therapies for these patients are remarkably effective, and we’ve seen disappointing (though still very limited) results with immunotherapy overall in these populations.  Importantly, we must remember that good results with first line Keytruda are seen thus far only in the high PD-L1 expression group, the 30% of patients with the best probability of benefit from immunotherapy, and that we can’t presume that immunotherapy would be better for the 70% of patients with a lower probability of benefiting greatly from immunotherapy.

And that brings us to the humbling results of the Checkmate-026 trial of Opdivo vs. chemotherapy, which I’ll cover in a post later this month.


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