David R. Jones, MD, and Roy S. Herbst, MD, PhD, prepared useful practice aids pertaining to lung cancer for this CME activity titled "Turning Tides in Targeted Therapy for Early-Stage EGFR-Mutated NSCLC: Latest Data and Practical Guidance for Thoracic Surgeons and the Multidisciplinary Team on the Emerging Role of EGFR-Targeted Therapy in Resectable Lung Cancer." For the full presentation, complete CME information, and to apply for credit, please visit us at https://bit.ly/2PSVELG. CME credit will be available until November 9, 2021.

1. First-Generation
Reversible EGFR TKIs
Second-Generation
Irreversible EGFR TKIs
Third-Generation
Irreversible EGFR TKI
EGFR TKI + VEGFR2
Antagonist
Gefitinib AfatinibErlotinib Dacomitinib
Erlotinib + RamucirumabOsimertinib
• 1L for EGFR exon
19 deletions or
L858R mutations
• 1L for EGFR exon
19 deletions or
L858R mutations
• 1L for EGFR exon
19 deletions or
L858R, S768I, L861Q,
and/or G719X mutations
• 1L for EGFR exon
19 deletions or
L858R mutations
• 1L for EGFR exon 19 deletions or
L858R mutations
• Treatment of T790M-positive NSCLC with
progression on or after EGFR TKI therapy
• 1L for EGFR exon 19 deletions or
L858R mutations
Current Approvals and Indications of Therapies
for Metastatic EGFR-Mutated NSCLC1
Full abbreviations, accreditation, and disclosure information available at PeerView.com/ZUJ40
1. https://www.fda.gov/drugs/resources-information-approved-drugs/hematologyoncology-cancer-approvals-safety-notifications.

2. Addressing Unmet Needs and Improving
Outcomes in Early-Stage NSCLC:
The Emerging Role of EGFR-Targeted Therapy
Full abbreviations, accreditation, and disclosure information available at PeerView.com/ZUJ40
NSCLC 5-Year Overall Survival
About 30% of patients with NSCLC present with resectable disease at diagnosis1-3
Surgery with curative intent is the primary treatment for these patients4
Adjuvant cisplatin-based chemotherapy is recommended for patients with
resectable stage II-IIIA NSCLC and select patients with stage IB disease5
Adjuvant impact depends on stage, and there is much room for improvement6
Rates of disease recurrence following surgery remain high across disease
stages, regardless of postoperative chemotherapy use7
Stage I (IB) Stage II Stage III
CALGB
JBR.10
ALPI
IALT
ANITA
LACE
34 57 9
30 7 63
36 60 4
33 65 2
36 60
33 64 3
32 45 23
53 32 15
53 43 4
43 39 18
51 39 10
76 19 5
55 30 15
51 26
61 26 13
234
Death (%) with/without chemotherapy
Survival without chemotherapy
Survival due to chemotherapy
Death due to chemotherapy

3. Addressing Unmet Needs and Improving
Outcomes in Early-Stage NSCLC:
The Emerging Role of EGFR-Targeted Therapy
Full abbreviations, accreditation, and disclosure information available at PeerView.com/ZUJ40
ADAURA: Phase 3 Double-Blind Studya
DFS According to Investigator Assessment10
Stage II to IIIA Disease Stage IB to IIIA Disease
Adjuvant osimertinib is the first
targeted agent to show a statistically
significant and clinically meaningful
improvement in disease-free
survival (DFS) in patients with stage
IB/II/IIIA EGFRmut NSCLC10
EGFR TKIs are standard of care for patients with EGFRmut
advanced NSCLC
Previous studies have suggested there may be a role for EGFR
TKIs in the resected setting, but results have been inconclusive8,9
ADAURA: Based on efficacy and safety data, adjuvant osimertinib
represents a big opportunity to improve outcomes in more
patients with early-stage NSCLC10
At 24 months, 90% of the
patients with stage II to IIIA
disease in the osimertinib
group (95% CI, 84-93) and
44% of those in the placebo
group (95% CI, 37-51) were
alive and disease free (overall
HR for disease recurrence or
death, 0.17; 99.06% CI,
0.11-0.26; P < .001)
→ This HR = 83% reduction
in risk of disease recurrence
or death
In the overall population, 89% of the
patients in the osimertinib group
(95% CI, 85-92) and 52% of those in
the placebo group (95% CI, 46-58)
were alive and disease free at 24
months (overall HR for disease
recurrence or death, 0.20; 99.12%
CI, 0.14-0.30; P < .001)
→ This HR = 80% reduction in risk
of disease recurrence or death
R
• Primary endpoint: DFS, by investigator assessment, in stage II/IIIA patients; designed for
superiority under the assumed DFS HR of 0.70
• Secondary endpoints: DFS in the overall population;f DFS at 2, 3, 4, and 5 years; OS; safety;
health-related quality of life
• Following IDMC recommendation, the study was unblinded early because of efficacy; here, an unplanned interim analysis is reported
• At the time of unblinding, the study had completed enrollment and all patients were followed up for at least 1 year
Patients with completely resected stageb
IB, II, IIIA NSCLC, with or without adjuvant
chemoc
Key inclusion criteria:
• ≥18 y (Japan/Taiwan, ≥20 y)
• WHO performance status 0/1
• Confirmed primary nonsquamous NSCLC
• Ex19del/L858Rd
• Brain imaging, if not completed
preoperatively
• Complete resection with negative marginse
• Maximum interval between surgery and
randomization: 10 wk without adjuvant
chemo; 26 wk with adjuvant chemo
Placebo
Once daily
Osimertinib
80 mg, once daily
Stratified by:
• Stage
(IB vs II vs IIIA)
• EGFRmut
(ex19del
vs L858R)
• Race
(Asian
vs non-Asian)
1:1
Planned treatment duration: 3 y
Treatment continues until:
• Disease recurrence
• Treatment completed
• Discontinuation criterion met
Follow up:
• Until recurrence: week 12 and
24, then every 24 weeks to 5
years, then yearly
• After recurrence: every 24
weeks for 5 years, then yearly
N = 682
Time Since Randomization, mo
ProbabilityofDFS
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
0 6 12 18 24 30 36 42 48
97%
90%
80%
61%
44%
28%
1.0
Osimertinib
Placebo
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
0 6 12 18 24 30 36 42 48
Time, mo
ProbabilityofDFS
97%
89%
79%
69%
53%
41%
Osimertinib
Placebo

4. Subgroup HR 95% CI
Overall (N = 682)
Stratified log-rank
Unadjusted Cox PH
0.21
0.20
0.16-0.28
0.14-0.29
Sex
Male (n = 204)
Female (n = 478)
0.21
0.20
0.11-0.38
0.12-0.30
Age
<65 y (n = 380)
≥65 y (n = 302)
0.18
0.24
0.10-0.28
0.14-0.38
Smoking status
Smoker (n = 194)
Nonsmoker (n = 488)
0.14
0.23
0.06-0.27
0.15-0.34
Race
Asian (n = 434)
Non-Asian (n = 248)
0.22
0.17
0.14-0.33
0.08-0.31
Stage
Stage IB (n = 212)
Stage II (n = 236)
Stage IIIA (n = 234)
0.50
0.17
0.12
0.25-0.96
0.08-0.31
0.07-0.20
EGFRmut
Exon 19 deletion (n = 378)
L858R (n = 304)
0.12
0.35
0.07-0.20
0.21-0.55
Adjuvant chemo
Yes (n = 378)
No (n = 304)
0.18
0.23
0.11-0.29
0.13-0.38
0.01 0.1 1
Favors osimertinib Favors placeboHR for DFS (95% CI)
Subgroup Analysis of Disease Recurrence or Death
According to Investigator Assessment10
Benefit favoring osimertinib with respect to disease-free survival was observed
consistently across all predefined subgroups
Safety profile was consistent with the established safety profile of osimertinib,
with mild EGFR TKI class effects reported
• Patients who received osimertinib had fewer local/regional and distant relapses
than those who received placebo, with a lower incidence of metastatic disease
in those patients with recurrence, including fewer CNS recurrence events
• Adjuvant osimertinib demonstrated a clinically meaningful improvement in CNS
DFS compared with placebo HR = 0.18 (95% CI, 0.10-0.33; P < .0001) = 82%
reduction in risk of CNS disease recurrence or death
Consistent improvement in DFS was seen regardless of whether patients received
prior adjuvant chemotherapy
DFS Per Investigator Assessment With and
Without Adjuvant Chemotherapy10
Adverse Events10
CNS DFS According to Investigator Assessment
in the Overall Population10
ADAURA → Adjuvant osimertinib represents a highly effective treatment for patients with stage IB/II/IIIA EGFRmut NSCLC after complete resection
0
0.2
0.4
0.6
0.8
1.0
0 6 12 18 24 30 36 42 48 56
ProbabilityofDFS
Time, mo
0
0.2
0.4
0.6
0.8
0 6 12 18 24 30 36 42 48
ProbabilityofDFS
Time, mo
DFS in Patients
Who Received Adjuvant Chemo
DFS in Patients Who Did Not
Receive Adjuvant Chemo
Osimertinib
Placebo HR = 0.16 (95% CI, 0.10-0.26)
Osimertinib
Placebo HR = 0.23 (95% CI, 0.13-0.40)
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
0 6 12 18 24 30 36 42 48
ProbabilityofCNSDFS
Time, mo
100% 98% 98%
97%
85% 82%
Osimertinib (N = 337), N (%) Placebo (N = 343), N (%)
Adverse Event Any Grade Grade 1 Grade 2 Grade 3 Any Grade Grade 1 Grade 2 Grade 3
Diarrhea 156 (46) 116 (34) 32 (19) 8 (2) 68 (20) 54 (16) 13 (4) 1 (<1)
Paronychia 85 (25) 31 (9) 50 (15) 3 (1) 5 (1) 3 (1) 2 (1) 0
Dry skin 79 (23) 75 (22) 3 (1) 1 (<1) 22 (6) 18 (5) 4 (1) 0
Pruritus 65 (19) 49 (15) 16 (5) 0 30 (9) 28 (8) 2 (1) 0
Cough 62 (18) 43 (13) 19 (6) 0 57 (17) 42 (12) 15 (4) 0
Stomatitis 59 (18) 35 (10) 18 (5) 6 (2) 14 (4) 10 (3) 4 (1) 0
Nasopharyngitis 47 (14) 30 (9) 17 (5) 0 35 (10) 25 (7) 10 (3) 0
Upper respiratory infection 45 (13) 24 (7) 19 (6) 2 (1) 35 (10) 19 (6) 16 (5) 0
Decreased appetite 44 (13) 29 (9) 13 (4) 2 (1) 13 (4) 9 (3) 4 (1) 0
Mouth ulceration 39 (12)
37 (11)
32 (9) 7 (2) 0 8 (2) 6 (2) 2 (1) 0
Dermatitis acneiform 29 (9) 8 (2) 0 16 (5) 12 (3) 4 (1) 0
1.0
a
NCT0251106; ADAURA data cutoff: January 17, 2020. b
AJCC, 7th edition. c
Prior, post, and planned radiotherapy was not allowed. d
Centrally confirmed in tissue. e
Patients received a CT after resection and within 28 days before treatment.f
Stage IB/II/IIIA.
1. Datta D, Lahiri B. Chest. 2003;123:2096-2103. 2. Le Chevalier T. Ann Oncol. 2010;21(suppl 7):vii196-vii198. 3. Cagle PT et al. Arch Pathol Lab Med. 2013;137:1191-1198. 4. Chansky K et al. J Thorac Oncol. 2017;12:1109-1121. 5. Postmus PE et al. Ann Oncol. 2017;28(suppl 4):iv1-iv21. 6. Kris
MG et al. J Clin Oncol. 2017;35:2960-2974. 7. Pignon J et al. J Clin Oncol. 2008;26:3552-3559. 8. Wu Y-L et al. J Clin Oncol. 2020;38(suppl 15):9005. 9. Huang Q et al. Chest. 2016;149:1384-1392. 10. Wu Y et al. N Engl J Med. 2020;383:825-835.
Addressing Unmet Needs and Improving
Outcomes in Early-Stage NSCLC:
The Emerging Role of EGFR-Targeted Therapy
Full abbreviations, accreditation, and disclosure information available at PeerView.com/ZUJ40