Dr. Jack West offers a list of 10 of the most important, timely abstract presentations in lung cancer, both non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), at the annual ASCO 2014 conference.

1. 10 Key ASCO 2014 Presentations
in Lung Cancer: NSCLC and SCLC
H. Jack West, MD

2. • With space to prioritize just 10 key presentations, multiple
important trials that have already been reported in press
releases as negative were not included.
• Trials that provided longer follow up or convey variations of
results already presumed or known were not prioritized.
• Accordingly, even though there will be several
immunotherapy trials with several previously identified and
some new immune checkpoint inhibitor agents, none really
breaks new ground. Immunotherapy hasn’t lost any
momentum, but the story is still being written.
Introductory comments on
some notable omissions

3. Tarceva (Erlotinib) +/- Avastin (Bevacizumab)
In EGFR Mutation-Positive Adv NSCLC
Kato, Abstract #8005
Oral Session, Monday, June 2
154 Japanese
EGFR Mutation-Pos Pts,
Advanced NSCLC
Previously Untreated
R
A
N
D Tarceva 150 mg by mouth daily
Tarceva 150 mg by mouth daily +
Avastin 15 mg/kg IV every 3 weeks
• Key results:
– Median PFS* 16.0 mo w/combo vs. 9.7 mo for Tarceva (HR^ = 0.54)
– Differences by EGFR mutation subtype
• Exon 19: Median PFS 18.0 vs. 10.3 mo
• Exon 21: Median PFS 13.9 vs. 7.1 mo
• Overall Survival not reported, but remarkable improvement in PFS
for Tarceva/Avastin in EGFR Mut+ NSCLC, & differences between
exon 19 and exon 21 mutations
*Progression-Free Survival ^Hazard Ratio

4. Combined Analysis of Afatinib vs. Chemo
in EGFR Mutation-Positive Adv NSCLC
• Pooled analysis shows significantly longer overall survival
benefit with afatinib, 27.3 vs. 24.3 mo (HR = 0.81)
• OS benefit with afatinib is actually seen entirely in exon
19 patients (HR 0.59), while there is actually no benefit
(and trend in detrimental direction) in exon 21 patients
(HR 1.25)
Yang, Abstract #8004
Metastatic NSCLC Oral Session, Monday, June 2
631 pts w/exon 19 or 21 EGFR
mut’n, combined from 2 trials
(LUX-Lung-3, LUX-Lung-6)
R
A
N
D
Cisplatin/Pemetrexed (LUX-Lung-3)
or
Cisplatin/Gemcitabine (LUX-Lung-6)
Afatinib 40 mg by mouth

5. AZD9291 for EGFR Mutation-Positive Patients
with Acquired Resistance to EGFR TKI Therapy
Janne, Abstract #8009
Clinical Science Symposium, Saturday, May 31
199 EGFR Mut’n-Pos Pts,
Advanced NSCLC
Prior Progression on
EGFR Tyrosine Kinase
Inhibitor (TKI)
132 w/centrally confirmed
T790M mutation status
Dose escalation of oral AZD9291 from 20-240 mg/d
57 Rx’d with free base formulation up to 900 mg 2x/d
31 Rx’d with HBr formulation to to 1000 mg 2x/d
10 transitioned from free base to HBr formulation
• RR 51% among 177 evaluable patients, including brain metastases
– responses lasting up to 8 months and ongoing
• RR 64% among T790M+, 23% among T790M-
• Most side effects grade 1: diarrhea, rash, nausea, though 5 cases
of interstitial lung disease (ILD) being evaluated

6. Sequist, Abstract #8010
Clinical Science Symposium, Saturday, May 29
88 EGFR Mut’n Pos Pts,
Advanced NSCLC
Prior progression on
EGFR TKI
2/3 have T790M mutation
Dose escalation of CO1686 twice daily
57 Rx’d with free base formulation up to 900 mg 2x/d
31 Rx’d with HBr formulation to to 1000 mg 2x/d
10 transitioned from free base to HBr formulation
CO1686 for EGFR Mutation-Positive Patients
with Acquired Resistance to EGFR TKI Therapy
• Optimal dosing selected as 750 mg HBr, which was 3-fold higher
exposure to drug than free base formulation
• Leading side effects were nausea, fatigue, and high blood sugar
(each in 20-25% of patients)
• Responses seen in T790M+ pts treated w/free base 900 mg 2x/d
• Responses being seen w/free base, but most too early

7. Camidge, Abstract #8001
16 patients w/adv NSCLC
enrolled, limited to 13 positive
for c-MET amplification by FISH
(1 low; 6 intermed; 6 high)
Crizotinib 250 mg by mouth twice daily
Continue until disease progression or
prohibitive side effects
Metastatic NSCLC Oral Session, Monday, June 2
• XALKORI was originally developed as MET inhibitor but was
diverted as “accidental” ALK inhibitor
XALKORI (Crizotinib) for c-MET-Positive
Advanced NSCLC
• Among 12 patients evaluable for response, 4 responses (33%)
– 0 of 1 low, 1 (20%) w/intermediate, 3 (50%) w/high amplification
• Median duration of response 35 weeks (8 months)
• Most common side effects: diarrhea (50%), nausea (31%),
vomiting (31%), peripheral edema (25%) visual impairment (25%).

8. Perol, Abstract #LBA8007
Metastatic NSCLC Oral Session, Monday, June 2
~1200 pts with adv
NSCLC, Squamous & non-
squamous
Prior platinum-doublet chemo
R
A
N
D
Taxotere (docetaxel) IV every 3 weeks &
Ramucirumab IV every 3 weeks
Taxotere (docetaxel) IV every 3 weeks &
Placebo IV every 3 weeks
• Ramucirumab, now marketed as Cyramza for gastric cancer, is an
anti-angiogenic monoclonal antibody inhibitor of VEGF-R2
(similar to Avastin)
• Late-breaking abstract, so no details yet provided, but press
release in February reports trial is positive for significant
progression-free and overall survival benefit
• Positive result of targeted therapy combined with second line
chemo; also a rare positive trial for pts. w/squamous NSCLC
Ramucirumab for Second Line Treatment of
Advanced NSCLC: The REVEL Trial

9. SQUIRE Trial: Necitumumab + Cis/Gem Chemo
Leads to Survival Benefit in Squamous NSCLC
• Necitumumab is humanized anti-EGFR monoclonal antibody
(same mechanism of action as Erbitux (cetuximab))
Thatcher, Abstract #8008
Metastatic NSCLC Oral Session, Monday, June 2
1093 pts advanced
Squamous NSCLC
Previously untreated
R
A
N
D
Cisplatin/Gemcitabine every 3 wks x 6
& Necitumumab d1,8 IV every 3 wks
Cisplatin/Gemcitabine every 3 wks x 6
• Statistically significant (but not necessarily
clinically significant) improvement in overall
survival, progression-free survival
Necitumumab
until progression
• Absolute differences: median OS 11.5 vs. 9.9 mo; median OS 5.7
vs. 5.5 months, Response rate 31% vs. 29%

10. Prophylactic Cranial Irradiation (PCI) for
Resected Stage IIIA N2 NSCLC
• Closed early due to slow accrual
• Disease-free survival (DFS) significantly favors PCI:
– Median DFS 28.5 vs. 21.2 mo (HR 0.67, p = 0.37);
– 5 yr DFS 29.8 vs 18.5%
• 5 yr brain relapse rate 13.6 vs. 41.3% (P<0.0001)
• Median OS 31.2 vs. 27.4 mo (NS)
• PCI Side effects: nausea, headache, fatigue, usually mild
• Small numbers, but huge differences
Wang, Abstract #7508
Stage I-III NSCLC & SCLC Poster Highlights Session, Sunday, June 1
156 pts w/resected st IIIA N2
NSCLC, rec’d post-op chemo
No evidence of disease
R
A
N
D Observation
PCI (30 Gy over 10 fractions)

11. Seto, Abstract #7503
Stage I-III NSCLC & SCLC Oral Session, Monday, June 2
Planned enrollment of 330 pts
w/ES-SCLC and any response
to first line chemotherapy
Stopped early, after 163 pts
After futility analysis
R
A
N
D Observation
PCI (25 Gy over 10 fractions)
• PCI led to survival benefit in European trial of patients with ES-
SCLC, but no brain imaging done before study entry
• Was benefit actually from treating brain metastases?
• Though PCI significantly reduced risk of brain metastases (58%
vs. 32.4% at 12 mo, p < 0.001), it was associated with a 38%
decline in survival (median OS 10.1 vs. 15.1 mo) vs. observation
Harmful Effect of Prophylactice Cranial
Irradiation (PCI) for Extensive-Stage (ES-)SCLC

12. “Consolidation” Thoracic Radiation Therapy
(TRT) for Residual Chest Disease in ES-SCLC
• All patients also received PCI
Slotman, Abstract #7502
498 pts with ES-SCLC
Any response after 4-6
cycles chemo
R
A
N
D Observation
Thoracic Radiation Therapy
(30 Gy over 10 fractions)
• Significant improvement in prog-free survival (HR 0.73, p = 0.001).
• Overall survival curves overlap for first 9 months, then separate to
favor TRT; no difference in 1 yr survival, but 2 year survival diff is
13% vs. 3% (p = 0.004)
• Given results on PCI for ED-SCLC in Japan (Seto abstract), would
survival have been better without PCI given to all patients?
Stage I-III NSCLC & SCLC Oral Session, Monday, June 2
88% had
residual
thoracic
disease

13. For questions, comments, and
further information, check out
CancerGRACE.org