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My Top 5 Notable ASCO 2012 Abstracts in Metastatic NSCLC

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The annual conference of the American Society of Clinical Oncology in late spring is the biggest event in the cancer world, where more of the big trials are presented than at any other time all year.  In the lung cancer world, it’s looking like this one won’t be a blockbuster but will have some promising and interesting findings to discuss.  As a preview, I wanted to offer my top 5 for what I think will emerge as the most important results we’ll see, based on the recently released abstracts of the meeting.  Lung cancer is divided into two tracks: today, I’ll cover the metastatic lung cancer track, and then I’ll next offer a top 5 on the track covering stage I-III NSCLC, SCLC, and other less common thoracic cancers 

Without further adieu, here are my top 5 in metastatic NSCLC:

 1) Phase II double-blind, randomized study of selumetinib (SEL) plus docetaxel (DOC) versus DOC plus placebo as second-line treatment for advanced KRAS mutant non-small cell lung cancer (NSCLC).  Abstract #7503

 

Yes, it’s a positive trial for a patient group that has been left wondering for too long, “what treatment can be offered for my mutation?”.  KRAS mutations are the most common molecular marker in NSCLC, seen in about 20% of patients, but up until now, we’ve had to focus on their less than impressive response to treatments like EGFR inhibitors and, in some trials, standard chemotherapy.  This is a phase III randomized trial in which there is a 4 month improvement in overall survival (OS) when the oral MEK inhibitor selumitinib was added to standard Taxotere (note: Dr. Quesnelle provided a great introduction to MEK inhibitors here).  I’m looking forward to relaying details when this trial is presented on the afternoon of 6/4 by Dr. Pasi Janne of Dana Farber Cancer Institute.

 

2) Clinical activity and safety of anti-PD1 (BMS-936558, MDX-1106) in patients with advanced non-small-cell lung cancer (NSCLC). Abstract #7509

On Saturday, June 2nd, our friend, Dr. Julie Brahmer from Johns.Hopkins will present information on the early work done thus far on the anti-PD1 immune-based therapy BMS-936558,  also known as MDX-1106 in patients with advanced NSCLC.  The abstract reveals that it’s only 10 patients, but responses lasting six months or longer have been seen in 3 of 10, and this agent has significant activity in many other cancer types as well.  The investigators I’ve spoken with are very encouraged by the tolerability and the impressive responses they’ve seen, including in some patients who have received many prior therapies, and in whom we wouldn’t have many expectations of significant tumor shrinkage or prolonged non-progression. 

Her podcast based on a recent webinar she did on immunotherapies will also be available in the next few weeks.

 

3) A randomized phase III trial of single-agent pemetrexed (P) versus carboplatin and pemetrexed (CP) in patients with advanced non-small cell lung cancer (NSCLC) and performance status (PS) of 2.  Abstract #7506

Dr. Rogerio Lilenbaum has spoken to use about treatment for elderly patients, and at ASCO he’ll be presenting a phase III randomized study from a Brazilian consortium (he’s from Brazil and maintains connections to the Brazilian oncology community) that randomized patients with a performance status (PS) that has historically been thought of as very marginal for standard doublet chemo (PS2 on the ECOG scale) to either carboplatin/Alimta (pemetrexed) or Alimta alone.  Similar to the European randomized trial for elderly patients randomized to doublet vs. single agent chemo, this trial, to be presented on Monday 6/4, demonstrated a clear benefit for the doublet, with a doubling of median progression-free survival (PFS) from 3 to 6 months, and a 3.5 month improvement in median OS (5.6 vs. 9.1 months).   Though the question of single-agent vs. doublet for marginal PS patients has historically been very debatable, I think this trial will go a long way to ending that debate.  And PS 2 patients comprise a very significant minority of the patients we actually see in the real world.

 

4) TAILOR: Phase III trial comparing erlotinib with docetaxel in the second-line treatment of NSCLC patients with wild-type (wt) EGFR. Late Breaking Abstract  (LBA)#7501.

A European trial to be presented by Dr. Marina Garassino on Monday afternoon, the TAILOR trial will directly compare second line treatment with standard IV chemotherapy to oral targeted therapy in a molecularly selected population: the 90% of patients in populations outside of Asia who don’t have an EGFR mutation (EGFR wild type).  Because this is a late breaking abstract, we don’t have the results yet, but the findings will be important no matter what they are.  This question is very relevant for a basic question in daily management of advanced NSCLC.

 

5) LUX-Lung 3: A randomized, open-label, phase III study of afatinib versus pemetrexed and cisplatin as first-line treatment for patients with advanced adenocarcinoma of the lung harboring EGFR-activating mutations. Late Breaking Abstract (LBA)#7500

This is yet another trial of EGFR tyrosine kinase inhibitor (TKI) vs. conventional chemotherapy as first line treatment in patients with a known EGFR mutation, and four others have all been consistent in showing a very significantly higher response rate and longer progression-free survival for mutation-positive patients who received Iressa (gefitinib) (in two prior trials) or Tarceva (erlotinib) – though we haven’t see a difference in overall survival, presumably because just about all of these patients receiving first line chemotherapy cross over to EGFR inhibitor therapy next and can benefit comparably with the EGFR inhibitor given as second line treatment.

Though this is also a late-breaking abstract for which we won’t see the data until Monday afternoon, when it is presented by Dr. Yang from Taiwan, I think we can presume what the results will be.  It’s hard to imagine it not being positive for the primary endpoint of PFS, since every other trial with a remarkably similar design has been highly positive for a PFS benefit.   

So if we already know the answer to the question because we’ve seen the results of four similar trials, why is this trial in my top 5 (albeit at the end of the list)? First, it’s a second generation EGFR inhibitor, an irreversible inhibitor that is effective not only against EGFR but against other related receptors in the same family, so it might be more effective than first generation EGFR TKIs. Second, if this trial is positive, as it should be, I would imaging that it will lead to the approval of afatinib and its commercial availability, where I suspect it may also be used in combination with Erbitux (cetuximab) for patients with acquired resistance to a first generation EGFR TKI, based on the preliminary but very encouraging work presented at ASCO 2011.

 

Bonus/honorable mention:

 

Multiplex testing for driver mutations in squamous cell carcinomas of the lung. Abstract #7505

 

It’s still very preliminary work, but investigators from Memorial Sloan-Kettering will be presenting data from their pilot program of doing a battery of molecular tests on squamous NSCLC tumors in a program called “Squamous Cell Lung Cancer Mutation Analysis Project” (SQ-MAP) as an analogous effort to the previously described Lung Cancer Mutation Consortium that did a batter of molecular marker tests on lung adenocarcinoma tumors.  They claim that there are “actionable” targets in 60% of patients; however, the targets – FGF-1, PTEN, PIK3CA mutation, and KRAS – don’t actually have agents available to treat them right now.  Still, this effort is a promising step in extending the gains we’ve seen with molecular oncology in other areas of lung cancer into the understudied world of squamous NSCLC

 

You can get my updates right from the meeting, in real time, by following me on Twitter: @JackWestMD

I’ll turn next to my top 5 abstracts in stage I-III NSCLC, small cell lung cancer, and uncommon thoracic cancers.


7 Responses to My Top 5 Notable ASCO 2012 Abstracts in Metastatic NSCLC

  • certain spring says:

    Thank you, Dr West.
    For anyone who wants to search the database of ASCO abstracts, it’s here:
    http://abstract.asco.org/ConfCatView_114_S.html
    or here for metastatic NSCLC specifically:
    http://abstract.asco.org/CatAbstView_114_462_AA.html

  • neilb says:

    This isn’t going to impact many people, but there’s an abstract showing that crizotinib shows strong activity in the first 13 patients with the ROS1 mutation. Sounds promising, not unlike the crizotinib results with the EML4-ALK mutation.–Neil

  • Dr West says:

    I definitely think it’s interesting, but the main reason I didn’t include it is that the story has really already broken. It needs to be presented at ASCO, because very few oncologists who aren’t highly specialized in lung cancer know these results, but many of the people here (patients, caregivers, and faculty) already know about what will be presented at ASCO showing that the people with a ROS-1 rearrangement have a very high probability of response to XALKORI (crizotinib). In fact, I heard that the abstract about ROS-1 rearrangements and XALKORI averaged the best scores for interest in the grading by the committee that developed the program (specific to metastatic lung cancer)

    -Dr. West

  • neilb says:

    And that, in itself, says a great deal about how sites like GRACE (there really aren’t other sites LIKE GRACE) have changed the landscape.–Neil

  • richardry says:

    Does anyone know if antibody PD1 work with Xalkori, what would happen?

  • Dr West says:

    I’m nearly certain that this has never been tested and is unknown.

    -Jack

  • certain spring says:

    Just on the squamous tumours mutation testing project, #7505 – it may be too early to say anything useful about this work, but in due course it would be very interesting to hear more.

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