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Does Adding Avastin to Tarceva Help EGFR Positive Lung Cancer Patients?

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Drs. Nasser Hanna, Melissa Johnson and Jack West discuss results of a phase 2 trial presented at ASCO 2014 that studied if adding Avastin (bevicizumab) to Tarceva helped EGFR positive lung cancer patients increase progression-free survival. June 2014.

Primary endpoint: PFS by independent review


Should We Add Avastin (Bevacizumab) to Tarceva (Erlotinib) for EGFR Mutation-Positive NSCLC?

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I recently had the honor of providing the expert commentary at the ASCO 2014 conference on three high impact lung cancer presentations, all on the subject of treatment options for molecularly defined populations (EGFR and ALK). I’ll review the findings from these three abstracts and my perspective on each of these, starting with a very provocative presentation by Dr. Kato from Japan that attempted to ask the question of whether we should add Avastin (bevacizumab) to Tarceva (erlotinib) as first line therapy for EGFR mutation-positive advanced NSCLC.

There have been a few large trials that directly tested the combination of Tarceva/Avastin vs. Tarceva alone — one as second line treatment (called BeTa), and one as maintenance therapy (called ATLAS).  These have failed to demonstrate a significant benefit for the combination, but they were in molecularly unselected patients, meaning that they were a broad population and not just patients with a specific molecular feature like an activating EGFR mutation.  However, both of these trials provided hints that the combination appeared to be especially effective for specific patients, most likely those with an EGFR mutation. For instance, the BeTa trial showed that two particular clinically defined subsets demonstrated an overwhelming benefit for the combination over Tarceva alone — Asian or Pacific Islander, and never-smokers.  Of course, these are also two subgroups known to be highly enriched for having an activating an EGFR mutation.  The subgroup analysis also showed that the small subgroup with an EGFR mutation also did far better with the combination, corroborating our presumption about why the Asian/Pacific Islander and never-smoker groups did so well.

BeTa Trial Subsets

 

   

  Moreover, the same clinically defined subgroups — Asian or Pacific Islander, as well as never-smokers — were also the two standout subgroups that appeared to benefit most in the ATLAS trial. The subgroup analysis from that trial did not include an analysis by EGFR mutation, but I suspect it would have shown the same effect as seen in the BeTa trial. 

ATLAS trial subsets

 

 

Dr. Kato and colleagues looked specifically at the potential benefit of adding Avastin at 15 mg/kg IV once every three weeks to daily Tarceva at 150 mg daily as first line systemic therapy for advanced NSCLC patients with a prospectively identified EGFR mutation. They randomized 154 patients, of whom 152 received treatment, and demonstrated a rather remarkably improvement in median progression-free survival (PFS) of more than 6 months, increasing from a median of 9.7 months for Tarceva alone to 16.0 months with the Tarceva/Avastin combination. Though the response rate was not significantly different, about 2/3 of patients showing significant tumor shrinkage (called an objective response) in both groups, the disease control rate, which is the combination of patients who demonstrate tumor shrinkage with those who demonstrate at least stable disease, was different, favoring the combination, at 99% of patients on the combination showing tumor shrinkage or stable disease, vs. 88% for those receiving Tarceva alone.

Also quite interesting was the difference between the two common types of activating mutation.  Specifically, both subtypes of activating EGFR mutation — exon 19 deletion and L858R on exon 21 — demonstrated a major improvement in PFS with the combination compared with Tarceva alone. But the patients with an exon 19 deletion had a longer PFS compared with the exon 21 patients, whichever treatment they received.   The improvement in PFS was especially remarkable in exon 19 deletion patients, who actually demonstrated an improvement of nearly 8 months in median PFS, which was a full 18 months with the combination!

PFS by mutation subtype

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Is It Necessary for Early Stage Lung Cancer Patients to Get Molecular Testing for Their Tumors?

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If you were diagnosed with early stage lung cancer, should you receive molecular testing on your tumor in order to get targeted therapy? Dr. Joel Neal of Stanford University Medical Center discusses the reasons for and against it. February 2014.


Treating EGFR Patients After Tarceva Stops Working

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Tarceva (erlotinib) has greatly helped EGFR positive lung cancer patients, but eventually it stops working. Dr. Jonathan Goldman of UCLA Jonsson Comprehensive Cancer Center talks about the next generation EGFR inhibitors that may soon become available. February 2014.


Top 10 Key Presentations at ASCO 2014: Join Us for Discussion at Upcoming #LCSM Chat 5/22

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Top10ListEvery year, many of the most important developments in cancer care are presented at ASCO. This year, we’ve got what I think is a very important year in lung cancer, with several practice-changing results/. Impressively, this is a year in which the most important trials include some focusing on first line treatment of patients with an EGFR mutation, some on acquired resistance in EGFR mutation-positive patients, some work on MET as a target, a couple on patients with squamous NSCLC or general NSCLC that includes squamous and non-squamous NSCLC, one striking finding in stage III resected NSCLC, and even a couple of most immediately practice-changing results in small cell lung cancer.

I’ll clarify that, working within the limit of a top 10 list , I couldn’t include some notable but negative trials, particularly those for which we’ve already learned of their negativity in press releases. And while immunotherapies continue to demonstrate their promise, the presentations at ASCO this year really just reinforce what we’ve already seen.  Because they don’t break significant new ground, this isn’t a year when immunotherapy trials are in the top 10 — though I expect at leasat one or two among next year’s top 10 list.

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