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Dr. Jack West is a medical oncologist and thoracic oncology specialist, and Executive Director of Employer Services at the City of Hope Comprehensive Cancer Center in Duarte, CA.

Top 5 Notable Abstracts in the Small Cell Lung Cancer and Stage I-III NSCLC Track
Mon, 05/21/2012 - 21:36
Author
Howard (Jack) West, MD, Associate Clinical Professor, Medical Oncology, Executive Director, Employer Services, Founder, President and CEO of GRACE

Here are the 5 presentations at ASCO in stage I-III NSCLC and small cell lung cancer that I think are most interesting and relevant.  You'll note that several are "negative" trials -- blockbusters are hard to come by here -- but even trials that tell us what not to do are important.   And there are some hints of new approaches that could improve outcomes for patients.

1) Prognostic and predictive effects of KRAS mutation subtype in completely resected non-small cell lung cancer (NSCLC): A LACE-bio study. Abstract # 7007

Frances Shepherd from Toronto will be presenting this analysis of over 1500 patients from a collection of several trials of adjuvant chemotherapy, in which there were 300 KRAS mutations identified, of which 275 were on codon 12, 24 were on codon 13, and 1 was on codon 14.  Though we have historically not evaluated results based on individual KRAS mutations, this analysis reveals several interesting results.  While patients with KRAS wild type (no mutation) had a strong trend toward better survival with adjuvant chemo, patients with mutation on codon 12 received no benefit from adjuvant chemotherapy, and the patients with a mutation on codon 13, adjuvant chemotherapy was actually significantly detrimental.  Though these results are based on a relatively small number of patients with a codon 13 mutation, it highlights the relevance of the particular type of KRAS mutation and also provides evidence that patients with KRAS mutations in general don’t benefit from adjuvant chemotherapy. 

 

2) SWOG 0802: A randomized phase II trial of weekly topotecan with and without AVE0005 (aflibercept) in patients with platinum-treated extensive-stage small cell lung cancer (E-SCLC). Abstract #7005

It’s only a randomized phase II trial with 98 enrolled patients, but it’s a very encouraging result from the Southwest Oncology Group, with a three-month progression-free survival of 26% when the anti-angiogenic agent aflibercept is added to topotecan, compared with 9% for topotecan alone.  The disease control rate (significant tumor shrinkage or stable disease) was 28% for the combination vs. 12% with topotecan alone.  There wasn’t evidence of a survival benefit, but these results are still promising enough that I would envision a randomized phase III trial being developed quickly that could potentially lead to a new agent becoming available for relapsed SCLC.

 

3) Accuracy of FDG-PET to diagnose lung cancer in the ACOSOG Z4031 trial. Abstract #7008.

Unfortunately, the title omits the key conclusion, which is “not so much”. This analysis looks specifically at the performance of PET scans to predict the probability that an apparently node-negative lung lesion was cancer, using a breakdown by maximum standard uptake value to estimate probability of cancer as follows:

 

SUV/PET avidity                                             Interpretation

0  (no PET avidity)                                    not cancer

>0 and <2.5 (low avidity)                       likely not cancer

2.5 – 5 (avid)                                              probably cancer

>5 (highly avid)                                         probably cancer

Using this estimate, the results from 682 PET scans were pretty inaccurate, particularly in determining which people didn’t have the disease.  There were quite a few “false positive” PET scans, and 17% of the surgeries were done for something that turned out to not be cancer.      

Results from the PET were more accurate for larger tumors, but the results here looked worse than in some other trials of PET scans, perhaps because PET scanning is less accurate for determining the probability of cancer in solitary nodules than for confirming the extent of a more widespread cancer.

Since it's easy to become very focused on PET scan results in the setting of ambiguous lung nodules, I think it's important to recognize the limitations of PET scans here.

 

4) The SELECT study: A multicenter phase II trial of adjuvant erlotinib in resected epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC). Abstract #7010 

The question of whether patients with an EGFR mutation might be well served or actually harmed from adjuvant maintenance EGFR tyrosine kinase inhibitor (TKI) therapy remains an open question, and one we field here pretty frequently. Most lung cancer specialists are wary about considering adjuvant EGFR TKI therapy outside of a trial setting, even for patients with an EGFR mutation, based on the surprising finding of a clear trend toward a detrimental effect on the BR.19 trial.

Dr. Joel Neal from Stanford (who will be one of our two presenters for our late June webinar program on lung cancer highlights from ASCO) will be presenting the results for 36 patients with an EGFR mutation who underwent resection of a stage IA-IIIA NSCLC, received any chemo and radiation recommended, and then received maintenance Tarceva (erlotinib) for up to two years.  Though the two-year disease-free survival is 94%, which is higher than would be expected, there are some cautionary notes in interpreting these results too favorably.  More than half of the patients had a stage I cancer, so this population may have had a lower risk of recurrence because of that; nearly 1/3 of the patients discontinued treatment before two years because of side effects; and there was a high rate of recurrence in the year after the Tarceva was discontinued (perhaps the same phenomenon seen on the BR.19 trial?).  We need to learn more, and we’ll see details Sunday, June 3rd.

 

5) A phase III study comparing amrubicin and cisplatin (AP) with irinotecan and cisplatin (IP) for the treatment of extended-stage small cell lung cancer (ED-SCLC): JCOG0509. Abstract #7003.

This Japanese randomized phase III trial of first line cisplatin-amrubucin compared with cisplatin-irinotecan, the standard treatment approach for extensive disease SCLC in Japan, failed to show a benefit for the investigational arm with amrubicin.  In fact, it demonstrated a surprisingly inferior overall survival (median 18.3 vs. 15.0 months).  It’s a negative result, but it’s still valuable information about the role of amrubicin in SCLC.

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