7. Multidisciplinary Integration of
Biomarker Testing in Early-Stage NSCLC
Pulmonologist
Interventional radiologist
Surgeon
Pathologist
Radiologist
Nuclear medicine
Pulmonologist
Thoracic surgeon
Multidisciplinary
team
(tumor board)
Referring
physician
Med oncologist
Thoracic surgeon
Radiation oncologist
Pulmonologist
Radiologist
Pathologist
Goal: Maximize “cure” rateIdentify pt
Select diagnostic
strategy
Biopsy
Histology
evaluation
Determine
Extent (TNM)
Assess
resectability
Radiologist
Nuclear medicine
Pulmonologist
Thoracic surgeon
Ancillary studies
8. Lung cancer toolkit
What’s needed to treat
Staging procedures
Seek metastatic disease
- Scenario: Supected early disease
PET-CT
If available
Brain MRI
Not everyone agrees
Mediastinoscopy
Before definitive surgery,
to avoid N3 (unresectable)
disease.
9. T – Primary Tumour
Tx Primary tumour cannot be assessed
T0 No evidence of primary tumour
T1 Tumour 3 cm or less in greatest diameter surrounded by lung or visceral pleura, without evidence
of main bronchus
T1a(mi) Mininally invasive adenocarcinoma
T1a Tumour 1 cm or less in greatest diameter
T1b Tumour more than 1 cm but not more than 2 cm
T1c Tumour more than 2 cm but not more than 3 cm
T2 Tumour more than 3 cm but not more than 5 cm; or tumour with any of the following features:
Involves main bronchus (without involving the carina), invades visceral pleura, associated with
atelectasis or obstructive pneumonitis that extends to the hilar region
T2a Tumour more than 3 cm but not more than 4 cm
T2b Tumour more than 4 cm but not more than 5 cm
T3 Tumour more than 5 cm but not more than 7 cm or one tha directly invades any of the following:
chest wall, phrenic nerve, parietal pericardium, or associated separate tumour nodule(s) in the
same lobe as the primary
T4 Tumours more than 7 cm or one that invades any of the following: diaphragm, mediastinum,
heart, great vessels, trachea, recurrent laryngeal nerve, oesophagus, vertebral body, carina;
separate tumour nodule(s) in a different ipsilateral lobe to that of the primary
10. N – Regional Lymph Nodes
Regional lymph nodes cannot be assessedNx
No regional lymph node metastasisN0
Metastasis in ipsilateral peribronchial and/or ipsilateral hilar lymph nodes
and intrapulmonary nodes, including involvement by direct extension
N1
Metastasis in ipsilateral mediastinal and/or subcarinal lymph node(s)N2
Metastasis in contralateral mediastinal, contralateral hilar, ipsilateral or
contralateral scalene or supraclavicular lymph node(s)
N3
M – Distant Metastasis
No distant metastasisM0
Distant metastasisM1
Separate tumour nodule(s) in a contralateral lobe; tumour with pleaural or
pericardial nodules or malignant pleural or pericardial effusion
M1a
Single extrathoracic metastasis in a single organM1b
Multiple extrathoracic metastases in one or several organsM1c
International Association for the Study of Lung Cancer, 2015
11. 8th Edition of the TNM Classification
for Lung Cancer
N0 N1 N2 N3 M1a M1b M1c
T1a IA1 IIB IIIA IIIB IVA IVA IVB
T1b IA2 IIB IIIA IIIB IVA IVA IVB
T1c IA3 IIB IIIA IIIB IVA IVA IVB
T2a IB IIB IIIA IIIB IVA IVA IVB
T2b IIA IIB IIIA IIIB IVA IVA IVB
T3 IIB IIIA IIIB IIIC IVA IVA IVB
T4 IIIA IIIA IIIB IIIC IVA IVA IVB
International Association for the Study of Lung Cancer, 2015
12. Place your patient where she/he belongs
Early Stage NSCLC (All)
Non-T4.
Non-N3
Non-M1
Mostly, Non-N2
Locally-Advanced NSCLC
M0 (a must)
T4 or
N3 or
Unresectable N2 (ie, bulky)
Advanced-NSCLC
M1 (a must)
13.
14. Multidisciplinary Integration of
Biomarker Testing in Early-Stage NSCLC
Pulmonologist
Interventional radiologist
Surgeon
Pathologist
Radiologist
Nuclear medicine
Pulmonologist
Thoracic surgeon
Multidisciplinary
team
(tumor board)
Referring
physician
Med oncologist
Thoracic surgeon
Radiation oncologist
Pulmonologist
Radiologist
Pathologist
Goal: Maximize “cure” rateIdentify pt
Select diagnostic
strategy
Biopsy
Histology
evaluation
Determine
Extent (TNM)
Define therapy
Early stage
Multidisciplinary
team
(tumor board)
Assess
resectability
Radiologist
Nuclear medicine
Pulmonologist
Thoracic surgeon
Ancillary studies
15. 8th Edition of the TNM Classification
for Lung Cancer
N0 N1 N2 N3 M1a M1b M1c
T1a IA1 IIB IIIA IIIB IVA IVA IVB
T1b IA2 IIB IIIA IIIB IVA IVA IVB
T1c IA3 IIB IIIA IIIB IVA IVA IVB
T2a IB IIB IIIA IIIB IVA IVA IVB
T2b IIA IIB IIIA IIIB IVA IVA IVB
T3 IIB IIIA IIIB IIIC IVA IVA IVB
T4 IIIA IIIA IIIB IIIC IVA IVA IVB
International Association for the Study of Lung Cancer, 2015
Upfront resection feasible
Mostly palliative intentMostly unresectable
16. Multidisciplinary Integration of
Biomarker Testing in Early-Stage NSCLC
Pulmonologist
Interventional radiologist
Surgeon
Pathologist
Radiologist
Nuclear medicine
Pulmonologist
Thoracic surgeon
Multidisciplinary
team
(tumor board)
Referring
physician
Med oncologist
Thoracic surgeon
Radiation oncologist
Pulmonologist
Radiologist
Pathologist
Goal: Maximize “cure” rateIdentify pt
Select diagnostic
strategy
Biopsy
Histology
evaluation
Determine
Extent (TNM)
Define therapy
Surgery
SBRT
Adjuvant Chemo
+/- RT
Early stage
Treat
Multidisciplinary
team
(tumor board)
Assess
resectability
Radiologist
Nuclear medicine
Pulmonologist
Thoracic surgeon
Ancillary studies
Thoracic surgeonPathologist
Histology
evaluation
Multidisciplinary
team
(tumor board)
17. 8th Edition of the TNM Classification
for Lung Cancer
N0 N1 N2 N3 M1a M1b M1c
T1a IA1 IIB IIIA IIIB IVA IVA IVB
T1b IA2 IIB IIIA IIIB IVA IVA IVB
T1c IA3 IIB IIIA IIIB IVA IVA IVB
T2a IB IIB IIIA IIIB IVA IVA IVB
T2b IIA IIB IIIA IIIB IVA IVA IVB
T3 IIB IIIA IIIB IIIC IVA IVA IVB
T4 IIIA IIIA IIIB IIIC IVA IVA IVB
International Association for the Study of Lung Cancer, 2015
Surgery, followed by adjuvant chemotherapy
Systemic therapyMultimodal therapy:
(ie, Chemo-Radiation, followed by Immunotherapy)
18. Consider surgery
Pneumonectomy
Lobectomy
+ Mediastinal LN dissection
Assess ability to undergo
surgery
Enough FEV1
Normal arterial CO2
Acceptable cardiac function
Acceptable PS
Early Stage NSCLC
Stages I and II, some stages III
Consider adjuvant platinum-doublet chemotherapy for stage II and III
Consider adjuvant radiotherapy if N+ or R1 resection
22. Multidisciplinary Integration of
Biomarker Testing in Advanced NSCLC
Adapted from Gandara D, et al. ASTRO/ASCO/IASLC
Symposium on Molecular Testing. 2012.
Pulmonologist
Interventional radiologist
Surgeon
Pathologist
Multidisciplinary
team
(tumor board)
Referring
physician
Med oncologist
Thoracic surgeon
Radiation oncologist
Pulmonologist
Radiologist
Pathologist
Palliative care
Goal: Identify “actionable” targets (ie, oncogenes)
Identify pt
Identify
target
lesion
Biopsy
Histology evaluation
Molecular biomarker
testing
23. Lung cancer toolkit
What’s needed to treat
Tissue diagnosis
Histology.
Morphology
Squamous
Adeno
NSCLC NOS
SCLC.
IHC
Squamous: p63-p40
Adeno: TTF+, Napsin
PD-L1 expression (mNSCLC)
SCLC: High Ki67, Chromogranin,
synaptophysin
Genotyping
Non-Squamous, advanced NSCLC
EGFR
ALK/EML4
ROS1, and others.
24. How to handle small tissue samples in lung cancer
p63 and TTF1
H&E
SCC Non-SCC (Adeno)
Genomics
SCLC
EGFR
ALK/EML4
ROS1
BRAF
Her2
p63+ TTF1+
PD-L1 by IHC
(in advanced NSCLC)
PD-L1 by IHC
(in advanced NSCLC)
Chromogranin
Synaptophysin
25. Therapeutic Decision Making
Histologic
Subtyping
Genotyping for
Predictive Biomarkers
These factors are interlinked and not independent
Adapted from Gandara DR, et al. Clin Lung Cancer. 2009;10:392-394.
Interlinking Themes in Therapeutic
Decision Making for Advanced NSCLC
26. What Tools Can Facilitate Personalized
Therapy in Advanced-Stage NSCLC?
• The questions:
• How do we optimize therapy in individual pts (ie, first line, second line,
third line)?
• How do we best integrate new diagnostic testing platforms for targeted
therapy or immunotherapy to achieve optimal results (eg, next-
generation sequencing in tissue or cell-free DNA in plasma)?
Chemotherapy Checkpoint InhibitorsTargeted Therapy
Genomics-driven
TKIs:
EGFR
ALK
ROS1
Histologic
subtyping for
chemotherapy
Anti–PD-1
Anti–PD-L1
Anti–CTLA-4
27. Tumor Cell
Cytotoxic T8
Lymphocyte
PD-L1
PD-1
- - -
Tumor Cell
Cytotoxic T8
Lymphocyte
+ + +
Active T-Cell anti-tumor
cytotoxicity
Inactive T-Cell anti-tumor
cytotoxicity
PD-1: Programmed cell death protein 1
(CD279)
Involved in regulating the immune
system’s response to cytotoxic T-cells
29. Multidisciplinary Integration of
Biomarker Testing in Advanced NSCLC
Adapted from Gandara D, et al. ASTRO/ASCO/IASLC
Symposium on Molecular Testing. 2012.
Pulmonologist
Interventional radiologist
Surgeon
Pathologist
Oncologist
Multidisciplinary
team
(tumor board)
Referring
physician
Med oncologist
Thoracic surgeon
Radiation oncologist
Pulmonologist
Radiologist
Pathologist
Palliative care
Goal: Identify “actionable” targets (ie, oncogenes)
Identify pt
Identify
target
lesion
Biopsy
Histology evaluation
Molecular biomarker
testing
Determine
therapy
30. Early Palliative Care for Patients with Metastatic
Non–Small-Cell Lung Cancer
Temel JS, NEJM, 2010
Early palliative: median OS: 11.6 mo
Standard care: median OS: 8.9 mo
HR: 1.7
Newly diagnosed
metastatic NSCLC
Early palliative
care
Standard
care
n=74
n=77
31. Multidisciplinary Integration of
Biomarker Testing in Advanced NSCLC
Adapted from Gandara D, et al. ASTRO/ASCO/IASLC
Symposium on Molecular Testing. 2012.
Pulmonologist
Interventional radiologist
Surgeon
Pathologist
Oncologist
Multidisciplinary
team
(tumor board)
Referring
physician
Med oncologist
Thoracic surgeon
Radiation oncologist
Pulmonologist
Radiologist
Pathologist
Palliative care
Goal: Identify “actionable” targets (ie, oncogenes)
Identify pt
Identify
target
lesion
Biopsy
Histology evaluation
Molecular biomarker
testing
Determine
therapy
33. •Untreated stage IV
NSCLC
•Non-squamous
•ECOG PS 0-1
•No significant
hemoptysis
1:1
Carboplatin + Paclitaxel
+ Bevacizumab
Carboplatin + Paclitaxel
+ Bevacizumab
ECOG 4599
Primary endpoint: OS
Sandler, A., Gray, R., Perry, M. C., Brahmer, J., Schiller, J. H., Dowlati, A., … Johnson, D. H. (2006). Paclitaxel–Carboplatin Alone or with Bevacizumab
for Non–Small-Cell Lung Cancer. New England Journal of Medicine, 355(24), 2542–2550. https://doi.org/10.1056/NEJMoa061884
Carbo/Pacli + Bevacizumab
(PCB): 1 year OS
34. •Untreated stage IV
NSCLC
•Non-squamous
•ECOG PS 0-1
•No significant
hemoptysis
1:1
Cisplatin + Pemetrexed
+ Maintenance Pemetrexed
Cisplatin + Pemetrexed
PARAMOUNT
Primary endpoint: OS
Sandler, A., Gray, R., Perry, M. C., Brahmer, J., Schiller, J. H., Dowlati, A., … Johnson, D. H. (2006). Paclitaxel–Carboplatin Alone or with Bevacizumab
for Non–Small-Cell Lung Cancer. New England Journal of Medicine, 355(24), 2542–2550. https://doi.org/10.1056/NEJMoa061884
Maintenance Pemetrexed
achieves > 1 yr OS
43. Multidisciplinary Integration of
Biomarker Testing in Advanced NSCLC
Adapted from Gandara D, et al. ASTRO/ASCO/IASLC
Symposium on Molecular Testing. 2012.
Pulmonologist
Interventional radiologist
Surgeon
Pathologist
Oncologist
Multidisciplinary
team
(tumor board)
Referring
physician
Med oncologist
Thoracic surgeon
Radiation oncologist
Pulmonologist
Radiologist
Pathologist
Palliative care
Goal: Identify “actionable” targets (ie, oncogenes)
Identify pt
Identify
target
lesion
Biopsy
Histology evaluation
Molecular biomarker
testing
Determine
therapy
Progression
rebiopsy
Determine
new therapy
Progression
rebiopsy
Treat
Treat
44. Relative Frequencies of Acquired
Resistance Mechanisms to EGFR TKIs
Yu HA, et al. Clin Cancer Res. 2013;19:2240-2247.
T790M
60%
HER2
8%
Unknown
18%
HER2 + T790M
4%
MET
amplification
3%
Small cell + MET
1%
Small cell
1%
Small cell +
T790M
2%
MET + T790M
3%
45. Liquid biopsy for T790M: Cobas EGFR Mutation Test V.2
Positive in 76.7% of tissue-positive specimens
Negative in 98.2% of tissue-negative
46. AURA 3: Osimertinib or Platinum–Pemetrexed in EGFR T790M–Positive
Lung Cancer
46
Osimertinib (n=279)
Platinum-pemetrexed
(n=140)
Basado en el análisis del investigador:
HR por progression de enfermedad o muerte,
0.30 (95% Cl, 0.23–0.41) P<0.001
Mediana PFS (95% Cl)
10.1 (8.3–12.3)
4.4 (4.2–5.6)
Probabilidaddesobrevidalibrede
progresión
1.
0
0.
8
0.
6
0.
4
0.
2
0
0 3 6 9 12 15 18
279
140
240
93
162
44
88
17
50
7
13
1
0
0
No. al riesgo
Osimertinib
Platinum-
pemetrexed
Meses
Mok, T. NEJM, 2017
51. Examples of PD-L1 IHC Staining of NSCLC Samples Using the Clinical
Trial Assay
Brown: PD-L1
staining
Blue color:
HNE
counterstain
PS < 1% PS 1% to 49% PS ≥ 50%
5 x
magnification
40 x
magnification
Garon EB, et al. N Engl J Med. 2015;372:2018-2028. Image courtesy of E. Garon.
52. Blueprint PD-L1 IHC Assay Comparison Project: Phase 1
▪ Analytical comparison of % tumor
cell staining (tumor proportion
score), by case (n = 39), for each
assay
▪ Data points represent the mean
score from 3 pathologists for each
assay on each case
▪ No clinical diagnostic cutoff applied
▪ Conclusion: 3 of 4 assays are
analytically similar for tumor cell
staining
22C3 (pembrolizumab), 28-8 (nivolumab), and
SP263 (durvalumab)
SP142 (atezolizumab)
Hirsch FR et al. J Thorac Oncol. 2017;12:208-222.
100
80
60
40
20
0
1 3 5 7 9 11 13 15 17 19
%TumorCellStaining
23 25 27 29 31 33 35 3721 39
22C3
28-8
SP142
SP263
54. •Untreated stage IV NSCLC
•PD-L1 TPS ≥50%
•ECOG PS 0-1
•No activating EGFR mutation or
ALK translocation
•No untreated brain metastases
•No active autoimmune disease
requiring systemic therapy
1:1
Pembrolizumab
Platinum-doublet
Chemotherapy
KEYNOTE-024
Primary endpoint: OS
Reck, M., Rodríguez-Abreu, D., Robinson, A. G., Hui, R., Csőszi, T., Fülöp, A., … Brahmer, J. R. (2016). Pembrolizumab versus Chemotherapy for PD-L1–Positive Non–Small-
Cell Lung Cancer. New England Journal of Medicine, 375(19), 1823–1833. https://doi.org/10.1056/NEJMoa1606774
Median OS with Pembrolizumab superior to chemo: 30 vs 14 months
(2017)
Brahmer JR, Rodríguez-Abreu D, Robinson AG, et al. Updated analysis of KEYNOTE-024:
pembrolizumab vs platinum-based chemotherapy for advanced NSCLC with PD-L1 TPS ≥50%.
Presented at: the IASLC 18th World Conference on Lung Cancer; October 15-18; Yokohama, Japan.
Abstract OA 17.06 (ID 9582).
Hazard ratio for death, 0.60;
95% CI, 0.41 to 0.89; P=0.005
55. Control
Targeted therapies
Immune checkpoint blockade
Combinations/sequencing
Survival
Time
Survival
Time
?
Modified from Ribas A, et al. Clin Cancer Res. 2012;18:336-341.
Survival Pattern with Chemotherapy (Control), Targetet therapies,
Immune checkpoint blockade and combinations (potential)
56. 56
KEYNOTE 001
W H Y P E M B R O L I Z U M A B I N N S C L C
L O N G - T E R M O S F O R P A T I E N T S W I T H A D V A N C E D N S C L C E N R O L L E D I N T H E K E Y N O T E - 0 0 1 S T U D Y O F
P E M B R O L I Z U M A B .
Leighl– ASCO 2017
A L I V E AT 3 Y E A R S
26%
58. KeyNote 189 - Pembrolizumab plus
Chemotherapy in Metastatic Non–Small-Cell
Lung Cancer
Gandhi, L., Rodríguez-Abreu, D., Gadgeel, S., Esteban, E., Felip, E., De Angelis, F., … Garassino, M. C. (2018). Pembrolizumab plus Chemotherapy in Metastatic Non–Small-Cell Lung Cancer. New England Journ
Metastatic nonsquamous NSCLC
No sensitizing EGFR or ALKmutations
Treatment-naive for metastatic NSCLC
ECOG PS 0/1
Measurable disease
Tumor sample for PD-L1 status available
No CNS metastasis symptoms
No significant autoimmune disease/treatment
2:1
Stratification
Smoking history
By PD-L1 expression (<1% vs ≥1%)
Cisplatin vs Carboplatin
Pembrolizumab + Pemetrexed +
Platin
Pemetrexed + Platin
Endpoints: Coprimary endpoints OS / PFS (by central review)
59. KeyNote 189 -
Pembrolizumab plus
Chemotherapy in
Metastatic Non–Small-
Cell Lung Cancer
Gandhi, L., Rodríguez-Abreu, D., Gadgeel, S., Esteban,
E., Felip, E., De Angelis, F., … Garassino, M. C. (2018).
Pembrolizumab plus Chemotherapy in Metastatic Non–
Small-Cell Lung Cancer. New England Journ
60. 60
KeyNote 189
P D - L 1 e x p r e s s i o n i n
<1% - 31%
1-49% - 31%
≥50% - 32%
Gandhi, L., Rodríguez-Abreu, D., Gadgeel, S., Esteban, E., Felip, E., De Angelis, F., … Garassino, M. C. (2018). Pembrolizumab plus Chemotherapy in Metastatic Non–
Small-Cell Lung Cancer. New England Journ
61. KeyNote 189 - Pembrolizumab plus Chemotherapy in
Metastatic Non–Small-Cell Lung Cancer
Gandhi, L., Rodríguez-Abreu, D., Gadgeel, S., Esteban, E., Felip, E., De Angelis, F., … Garassino, M. C. (2018). Pembrolizumab plus Chemotherapy in Metastatic Non–Small-Cell Lung Cancer. New England Journ
62. KeyNote 189 - Pembrolizumab plus Chemotherapy in Metastatic
Non–Small-Cell Lung Cancer
Gandhi, L., Rodríguez-Abreu, D., Gadgeel, S., Esteban, E., Felip, E., De Angelis, F., … Garassino, M. C. (2018). Pembrolizumab plus Chemotherapy in Metastatic Non–
Small-Cell Lung Cancer. New England Journ
63. KeyNote 189 - Pembrolizumab plus Chemotherapy in Metastatic
Non–Small-Cell Lung Cancer
Gandhi, L., Rodríguez-Abreu, D., Gadgeel, S., Esteban, E., Felip, E., De Angelis, F., … Garassino, M. C. (2018). Pembrolizumab plus Chemotherapy in Metastatic Non–
Small-Cell Lung Cancer. New England Journ
64. KeyNote 189 - Pembrolizumab plus Chemotherapy in Metastatic
Non–Small-Cell Lung Cancer
Gandhi, L., Rodríguez-Abreu, D., Gadgeel, S., Esteban, E., Felip, E., De Angelis, F., … Garassino, M. C. (2018). Pembrolizumab plus Chemotherapy in Metastatic Non–
Small-Cell Lung Cancer. New England Journ
PD-L1 <1% PD-L1 1-49%
PD-L1 ≥50%
65. 65
61.
71.
73.
52. 51.
48.
KeyNote 189
C h e m o + P e m b r o l i z u m a b i n m e t a s t a t i c N S C L C
1 2 - m o n t h O S i n P e m b r o l i z u m a b + C h e m o v s C h e m o
61%
52%
71%
51%
73%
48%
PD-L1 TPS <1% PD-L1 TPS 1-49% PD-L1 TPS ≥50%%
Pembro + Chemotherapy Chemotherapy
Gandhi, L., Rodríguez-Abreu, D., Gadgeel, S., Esteban, E., Felip, E., De Angelis, F., … Garassino, M. C. (2018). Pembrolizumab plus Chemotherapy in Metastatic Non–
Small-Cell Lung Cancer. New England Journ
66. KeyNote 189 - Pembrolizumab plus Chemotherapy in Metastatic
Non–Small-Cell Lung Cancer
Gandhi, L., Rodríguez-Abreu, D., Gadgeel, S., Esteban, E., Felip, E., De Angelis, F., … Garassino, M. C. (2018). Pembrolizumab plus Chemotherapy in Metastatic Non–
Small-Cell Lung Cancer. New England Journ
Overall Response Rate (by TPS)
67. KeyNote 189 - Pembrolizumab plus Chemotherapy in Metastatic
Non–Small-Cell Lung Cancer
Gandhi, L., Rodríguez-Abreu, D., Gadgeel, S., Esteban, E., Felip, E., De Angelis, F., … Garassino, M. C. (2018). Pembrolizumab plus Chemotherapy in Metastatic Non–
Small-Cell Lung Cancer. New England Journ
PFS
68. KeyNote 189 - Pembrolizumab plus Chemotherapy in Metastatic
Non–Small-Cell Lung Cancer
Gandhi, L., Rodríguez-Abreu, D., Gadgeel, S., Esteban, E., Felip, E., De Angelis, F., … Garassino, M. C. (2018). Pembrolizumab plus Chemotherapy in Metastatic Non–
Small-Cell Lung Cancer. New England Journ
In conclusion, in patients with metastatic nonsquamous NSCLC
without sensitizing EGFR or ALK mutations, the addition of
pembrolizumab to induction therapy with pemetrexed and a
platinum-based drug and to pemetrexed maintenance therapy
resulted in significantly longer overall survival and progression-
free survival and a higher response rate than the addition of
placebo at a cost of a low incidence of renal dysfunction at the
first interim analysis. The survival benefit for pembrolizumab-
combination therapy was observed across all categories of PD-L1
expression.
69. KeyNote 189 - Pembrolizumab plus Chemotherapy in Metastatic
Non–Small-Cell Lung Cancer
Gandhi, L., Rodríguez-Abreu, D., Gadgeel, S., Esteban, E., Felip, E., De Angelis, F., … Garassino, M. C. (2018). Pembrolizumab plus Chemotherapy in Metastatic Non–
Small-Cell Lung Cancer. New England Journ
In conclusion, in patients with metastatic nonsquamous NSCLC
without sensitizing EGFR or ALK mutations, the addition of
pembrolizumab to induction therapy with pemetrexed and a
platinum-based drug and to pemetrexed maintenance therapy
resulted in significantly longer overall survival and progression-
free survival and a higher response rate than the addition of
placebo at a cost of a low incidence of renal dysfunction at the
first interim analysis. The survival benefit for pembrolizumab-
combination therapy was observed across all categories of PD-L1
expression.
70.
71. Multidisciplinary Integration of
Biomarker Testing in Advanced NSCLC
Adapted from Gandara D, et al. ASTRO/ASCO/IASLC
Symposium on Molecular Testing. 2012.
Pulmonologist
Interventional radiologist
Surgeon
Pathologist
Oncologist
Multidisciplinary
team
(tumor board)
Referring
physician
Med oncologist
Thoracic surgeon
Radiation oncologist
Pulmonologist
Radiologist
Pathologist
Palliative care
Goal: Identify “actionable” targets (ie, oncogenes)
Identify pt
Identify
target
lesion
Biopsy
Histology evaluation
Molecular biomarker
testing
Determine
therapy
Progression
rebiopsy
Determine
new therapy
Progression
rebiopsy
Treat
Treat
72. mEGFR+…
mOS 30 mo,
and
improving
with anti-
EGFR
ALK+… mOS
>45 mo, and
improving
with anti-
ALK
PD-1>50%… mOS
30 mo, and
improving with
anti-PD-1
Non-Squamous… improved
OS with Chemo +
Pembrolizumab
mNSCLC
Only through accurate
histopathology,
genotyping and IHC can
these results be
achieved
SG = supervivencia global (OS = overall survival);
TRO=tasa de respuesta objetiva (ORR = objective response rate )
SLP= supervivencia libre de progresión (PFS = progression-free survival)
HR= Razón de riesgos (HR = hazard ratio)
NSCLC, non-small-cell lung cancer.
TKI, tyrosine kinase inhibitor.
Puntos de conversación
El punto final primario de AURA3 fue PFS por evaluación del investigador
Osimertinib mostró 10,1 meses de mediana de SLP en comparación con 4,4 meses con platino-pemetrexed (CRI de 0,30, P <0,001)
PFS por BICR fueron consistentes con la evaluación del investigador
Referencia
Mok TS, Wu Y-L, Ahn M-J, y col. Osimertinib o platino-pemetrexed en cáncer de pulmón EGFR T790M-positivo. N Engl J Med. 6 de diciembre de 2016. DOI: 10.1056 / NEJMoa1612674. [Epub antes de imprimir].