histology: its influence on therapeutic decision making...molecular profiling and therapeutic...
TRANSCRIPT
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Histology: Its Influence on
Therapeutic Decision Making
Mark A. Socinski, MD
Professor of Medicine and Thoracic Surgery
Director, Lung Cancer Section, Division of Hematology/Oncology
Co-Director, UPMC Lung Cancer Center of Excellence and Lung and Thoracic Malignancies Program
University of Pittsburgh
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Histology: Its Influence on
Therapeutic Decision Making
Mark A. Socinski, MD
Professor of Medicine and Thoracic Surgery
Director, Lung Cancer Section, Division of Hematology/Oncology
Co-Director, UPMC Lung Cancer Center of Excellence and Lung and Thoracic Malignancies Program
University of Pittsburgh
![Page 8: Histology: Its Influence on Therapeutic Decision Making...Molecular Profiling and Therapeutic Decision Making for Advanced NSCLC General Guidelines for 2013 • Who to test: patients](https://reader034.vdocuments.site/reader034/viewer/2022052010/601fa1276df29a7278613f39/html5/thumbnails/8.jpg)
Disclosures
Advisory Committee
Bristol-Myers Squibb Company, Daiichi Sankyo Inc, Lilly
Contracted Research
Bayer HealthCare Pharmaceuticals, Boehringer Ingelheim Pharmaceuticals Inc, Bristol-Myers Squibb Company, Celgene Corporation, Genentech BioOncology, GlaxoSmithKline, Lilly, Merck, Novartis Pharmaceuticals Corporation, Pfizer Inc, Roche Laboratories Inc, Synta Pharmaceuticals Corp
Speakers Bureau Celgene Corporation, Genentech BioOncology
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Overview of NSCLC Histologies
NSCLC adenocarcinoma
Adenocarcinoma is a malignant epithelial tumor with glandular differentiation or mucin production, showing acinar, papillary, bronchoalveolar, or solid with mucin growth patterns or a mixture of these patterns.
NSCLC large cell carcinoma
Large cell carcinoma is an undifferentiated non-small cell carcinoma that lacks the cytologic and architectural features of small cell carcinoma and glandular or squamous differentiation.
NSCLC squamous cell carcinoma
Squamous cell carcinoma is a malignant epithelial tumor showing keratinization and/or intercellular bridges that arise from bronchial epithelium. These features vary with degree of differentiation, being prominent in well-differentiated tumors and focal in poorly differentiated tumors.
Images copyright © 2007 Asterand PLC Pathology and Genetics of Tumours of the Lung, Pleura, Thymus and Heart. IARCPress. 2004:26-30.
Diagnostic Accuracy – influenced by type of biopsy procedure, quantity of tumor in the specimen, degree of tumor differentiation, use of ancillary studies, experience of the pathologist
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EASY CASES- MORPHOLOGY IS SUFFICIENT
SCLC ADC SQC
SQC- basaloid ADC-solid pattern LCNEC
NOT SO EASY CASES – IHC SHOULD HELP
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IMMUNOHISTOCHEMISTRY AND NSCLC
MARKER ADENOCARCINOMA SQUAMOUS CELL CARCINOMA
CK 7 ~90 ~20-30 CK5/6 10-20 ~100 P63 10-20 ~100
TTF-1 70-90 Almost never P40 Almost never ~100
Cytokeratin 20, Napsin A, surfactant A, Ber-EP4, B72.3, synaptophysin, chromogranin, CD56, CEA
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IMMUNOHISTOCHEMISTRY AND NSCLC- SMALL SPECIMENS
IHC 1 SQC/1 ADC and/or mucin
ADC IHC + or mucin+
SQC IHC -
NSCLC, favor ADC
SQC IHC + ADC
IHC - or mucin-
NSCLC, favor SQC
SQC IHC + ADC
IHC + or mucin+
NSCLC,NOS possible
adenosquamous
IHC- mucin -
NSCLC,NOS
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Small Biopsies/Mixed Histology
• Confidence in the diagnosis aids therapeutic choices .talk to your pathologist
• Clearly sampling bias is an issue • When uncertain, clinical factors must be considered - smoking status, age, co-morbidities, PS, etc • Optimize cytotoxic choices based on.. - efficacy (ORR, PFS, OS benefits) - toxicity • Second pathologic opinions can be helpful
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5 Reasons Why Medical Oncologists Care About Histology
• Reason #1 – Bevacizumab • Reason #2 – Pemetrexed • Reason #3 – Molecular testing • Reason #4 – nab-paclitaxel • Reason #5 - Necitumumab
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Reason #1: Bevacizumab in NSCLC: Bleeding in Randomized Phase II Trial • 6 life-threatening pulmonary hemorrhages; 4 fatal
– Overall incidence: 9% (6/66) – 5 occurred at bevacizumab 7.5 mg/kg
• Apparent risk factors – Baseline hemoptysis – Histology
• Squamous histology: 31% (4/13) • Nonsquamous histology: 4% (2/53)
Johnson. J Clin Oncol. 2004;22:2184; Sandler. ASCO. 2005 (abstr 4).
Chemotherapy-naïve stage IIIB (wet)
or IV NSCLC N=99
Carboplatin + Paclitaxel Placebo Bevacizumab
15 mg/kg
Carboplatin + Paclitaxel Bevacizumab 7.5 mg/kg
Carboplatin + Paclitaxel Bevacizumab 15 mg/kg
PD
PD=progressive disease.
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Reason #2: Cisplatin/Pemetrexed vs Cisplatin/ Gemcitabine in Advanced NSCLC: Results
1.23;1.00, 1.51
9.4;8.4, 10.2 10.8;9.5, 12.1
Survival Time (months) in Patients With SCC
Surv
ival
Pro
babi
lity
9.4 mos Median Survival
10.8 mos Adjusted HR CP vs CG
1.23
Squamous Nonsquamous
Median Survival
0.81;0.70, 0.94
Survival Time (months) in Patients With Nonsquamous Histology
Surv
ival
Pro
babi
lity
10.4 mos
0.81
11.8 mos
Adjusted HR CP vs CG
Scagliotti GV et al: J Clin Oncol. 26 (21), 2008: 3543-3551.
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Reason #3 – Molecular Testing
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Molecular Profiling and Therapeutic Decision Making for Advanced NSCLC
General Guidelines for 2013
• Who to test: patients with NSCLC and adenocarcinoma component
• What to test for: EGFR mutation and ALK fusion (+ others?)
• When to test: at the time of diagnosis (not just when treatment decision needed)
• What specimen: core needle biopsy (or multi-pass FNA), cytology cell block, surgical biopsy (bone biopsy problematic)
• How to test: concurrently (not sequentially test-by-test)
• How long a turnaround time is acceptable?: 2 weeks or less
• When to re-test: after a targeted therapy intervention (to assess for tumor evolution in the molecular profile)
Adapted from: CAP/IASLC/AMP Guidelines
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Socinski MA et al, Annals of Oncology, 24:2390-6, 2013
Reason #4: ORR by Histology: CbP vs Cb-nab-P in Advanced NSCLC
a 95% CIs for response rate ratios are calculated according to the asymptotic 95% CI of the relative risk of nab-PC to sb-PC.
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0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40
0
20
40
60
80
100
Reason #5: SQUIRE Primary Outcome: Overall Survival ITT1
GC+N N=545
GC N=548
Stratified HR (95% CI) 0.84 (0.74, 0.96) Stratified p-value (log-rank) 0.01 Median, months (95% CI) 11.5 (10.4, 12.6) 9.9 (8.9, 11.1)
Time Since Randomization (Months)
Ove
rall
Sur
viva
l (%
)
GC+N GC
1Thatcher N, et al. Lancet Oncol 2015;16(7):763-74
Necitumumab + Cis/Gem Vs Cis/Gem Alone in Stage IV Squamous Carcinoma
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Why Do Medical Oncologists Care About Histology?
• Molecular testing – Current guidelines recommend routine testing for
EGFR and ALK in adenocarcinoma • Therapeutic considerations
– Bevacizumab contraindicated in squamous histology due to risk of pulmonary hemorrhage
– Pemetrexed indicated in non-squamous histologies – Nab-P + Cb has superior ORR in squamous histology – Necitumumab indicated in squamous histology
• Prognosis – In general, individuals with non–squamous cell lung
cancer do slightly better than those with squamous cell
Lindeman et al, 2013, Scagliotti et al, 2008. Johnson et al, 2004. Thatcher et al, 2015
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Histology: Its Influence on
Therapeutic Decision Making
Mark A. Socinski, MD
Professor of Medicine and Thoracic Surgery
Director, Lung Cancer Section, Division of Hematology/Oncology
Co-Director, UPMC Lung Cancer Center of Excellence and Lung and Thoracic Malignancies Program
University of Pittsburgh
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