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Top 10 asco 2016 abstracts for lung cancer (and mesothelioma)
1. 10 Key Lung Cancer Abstracts
to be presented at ASCO 2016
H. Jack West, MD
Swedish Cancer Institute
Seattle, WA
#LCSM Chat
May 26, 2016
8 PM ET/5 PM PT
Join us!
2. Multikinase inhibitor vandetinib to treat
RET fusion-positive advanced NSCLC
Abstract #9012, Seto & colleagues
• RET fusion is a recently identified potential driver of NSCLC,
seen in 1-2% of cases
• Vandetinib is “multikinase inhibitor” of several targets, incl RET
• Test of vandetinib 300 mg daily in RET fusion+ NSCLC
• Screening of >1500 Japanese pts: 34 (2%) w/RET fusions
• 19 enrolled, 17 w/efficacy data available
• Response rate (RR) 53% and median progression-free surv
(PFS) 4.3 mo; of pts w/specific RET fusion (CCDC6-RET), RR
83% (5/6 pts); median PFS 8.3 months
• A promising agent for another rare molecular subgroup
3. PD-L1 inhibitor avelumab in malignant pleural
mesothelioma (MPM)
Abstract #8503, Hassan & colleagues
• Does immune checkpoint inhibitor therapy have significant
activity in unresectable MPM?
• 53 patients w/MPM, 81% w/epithelioid subtype
• No requirement for threshold PD-L1 expression
• Response rate (RR) & progression-free surv (PFS) assessed
• RR 9.4% (5/53), stable disease in 47.2%
• Median PFS 17 weeks
• No surprising side effects
• Modestly encouraging, but commentary following this is called
“Immunotherapy: Reality Check”.
4. Weekly Taxol (paclitaxel)/Avastin (bevacizumab)
vs. Taxotere (docetaxel) in 2nd
/3rd
Line NSCLC
Abstract #9005, Cortot & colleagues
• Is combination of weekly Taxol/Avastin (Taxol 3 weeks out of
4, Avastin every 2 weeks) superior to Taxotere every 3 weeks
as 2nd
or 3rd
line therapy for advanced NSCLC?
• 166 pts randomized, 2/3 to Taxol/Avastin, 1/3 to Taxotere
• 30% had received prior Avastin
• Progression-free survival (PFS) was primary endpoint
• Significantly superior PFS (median 5.4 vs. 3.9 mo) &
response rate (22.5% vs. 5.5%) for taxol/bev; no better surv
• Far less hematologic (blood counts) side effects w/taxol/bev,
but neuropathy, hypertension, many other side effects worse
w/taxol/bev
• A promising option for some, but not enough to change std Rx
5. Daily vs. twice daily (“hyperfractionated”) chest
radiation with chemo for limited disease SCLC
Abstract #8504, Faivre-Finn & colleagues
• A study published in the New England Journal of Medicine
(Turrisi, 1999) found better survival with twice daily chest
radiation combined with cisplatin/etoposide chemo
• This twice daily RT schedule has not been widely adopted
due to practical challenges, concerns for greater side effects,
and unequal radiation doses in NEJM paper giving daily RT
arm a disadvantage
• Randomized trial of 547 LD-SCLC pts to chemo + equal total
chest RT doses delivered once or twice daily
• No significant differences in survival or side effects; both
groups have better survival than historical numbers
6. Tagrisso for Leptomeningeal Carcinomatosis (LM) in
EGFR Mutation-Positive Advaced NSCLC
Abstract #9002, Yang & colleagues
• LM is seen in 3-5% of pts w/advanced NSCLC but 2-
3x more common in pts with EGFR mut-pos NSCLC
• 1st
or 2nd
gen EGFR inhibs don’t get across blood-brain
barrier well at standard dosing
• Is 3rd
gen EGFR inhib Tagrisso (osimertinib) more
effective: trial of Tagrisso 160 mg/d (2x std dose) in
LM
• 20 pts w/EGFR mut+ NSCLC & LM, most treated for
weeks to a few months
• 7/20 show imaging improvement, several also show
improvement in neuro Sx, reduction in # of cancer
cells in cerebrospinal fluid
• Preliminary, but encouraging results for LM
From Corbin & Nagpal, JAMA Onc 2016
7. Comparison of Tissue, Plasma, & Urine Testing for
EGFR T790M Trial with Rociletinib
Abstract #9001, Wakelee & colleagues
• T790M is acquired resistance mut’n seen in 50-60% of pts
w/EGFR mut’n-pos NSCLC progressing after 1st
or 2nd
gen
EGFR inhibitors. Rociletinib active in T790M+ acq’d resistance.
• How well do molecular testing approaches from plasma and
urine work for detecting T790M? Do outcomes in patients with
T790M detected in plasma and/or urine respond the same as
those patients with T790M detected from tissue.
• Plasma & urine detected T790M with sensitivity comparable to
that seen w/tissue, which can miss mutations due to tissue
heterogeneity; T790M+ pts found by plasma & urine have same
response rate & duration of response as T790M+ by tissue.
8. Local “consolidation” therapy of radiation or surgery
after first-line systemic therapy in met NSCLC
Abstract #9004, Gomez & colleagues
• Does local consolidation therapy with radiation or surgery in
pts w/up to 3 areas of residual disease after initial chemo or
targeted therapy go longer before progressing?
• 254 patients evaluated, 49 randomized to local Rx vs. no
• Progression-free survival (PFS) was primary endpoint
• Wide range of treatments delivered: surgery, radiation, or
both, at discretion of treating docs
• Trial stopped for marked benefit in PFS
• But is PFS a useful endpoint if the lesions that would be
progressing have been removed or irradiated? And is this
useful if <20% of patients considered get to randomization?
9. Addition of low molecular weight heparin to adjuvant
chemotherapy after surgery for early stage NSCLCÂ
Abstract #8506, Groen & colleagues
• Does addition of a low-molecular weight heparin during
adjuvant chemo improve recurrence-free survival (RFS) in pts
with resected early stage NSCLC & getting adjuvant chemo?
• 202 pts randomized to cis/gemcitabine (for squamous NSCLC)
or cis/Alimta (pemetrexed) (for non-squamous NSCLC), with
or without daily nadroparin under the skin daily x 16 weeks
• Higher neutropenia (low white blood cell count) level w/nadro,
but no other differences in side effects
• Median RFS 47.8 vs. 36.1 mo, 3 yr RFS 57% vs. 50%,
favoring nadroplatin
• Not likely to change practice yet, but very provocative
10. Rovalpituzumab tesirine in recurrent or refractory
small cell lung cancer (SCLC)Â
Abstract #LBA8505, Rudin & colleagues
• Rovalpituzumab tesirine (rova-T) is an “antibody-drug
conjugate”, an antibody linked to a chemotherapy agent. The
antibody for rova-T is to delta-like protein 3 (DLL3), a marker
seen in approximately 70% of SCLC tumors.
• Dr. Cathy Pietanza presented data in 2015 showing a
response rate of 23% in previously treated SCLC, but in
patients with DLL3-positive SCLC, the response rate was 44%
• No data available yet: this is a “late-breaking abstract”
• Among the most promising leads in SCLC; data coming at
ASCO 2016
11. J-ALEX: Alecensa (Alectinib) vs. Xalkori (Crizotinib)
as Initial ALK Inhibitor in ALK+ NSCLC
Abstract #9008, Nokihara & colleagues
• Is 2nd
gen ALK inhibitor Alecensa a superior first ALK inhibitor
in head to head comparison to Xalkori in pts w/ALK+ met
NSCLC?
• 207 patients in open-label randomized trial in Japan
• Progression-free survival (PFS) was primary endpoint
• Interim analysis shows highly significant improvement in PFS
(median 10.2 months vs. not yet reached), survival immature
• Side effect profile clearly favors Alecensa
• Should this change first line therapy for ALK+ NSCLC?