2. Objectives
List the etiology, risk factors/epidemiology, pathophysiology, staging,
prognostic factors, and clinical presentation of melanoma.
Name the usual treatment options for Stage III to Stage IV melanoma.
Describe the mechanism of action, dosing/administration, adverse
effects, and monitoring parameters of T-VEC.
Discuss the methods, results, and strengths/weaknesses of T-VEC in
clinical trials.
Summarize the author’s conclusions, relevance to pharmacy practice,
and student’s conclusions to these studies.
3. Melanoma
Etiology:
Unknown, though there may be contributing factors from
the environment and patient
UVB>UVA
Epidemiology:
Number of new cases: “21.6 per 100,000 men and women
per year (2008-2012)”~SEER Stat Facts Sheet
Deaths: “2.7 per 100,000 men and women per year”~SEER
Stat Facts Sheet
(Cancer.gov. [Internet]. Rockville, Marlyand. National Cancer Institute. c2012. SEER Stat Facts Sheet: Melanoma of the Skin National Cancer Institute; 2012. [cited 28 Feb
2016]; [about 2 screens]. Available from: http://seer.cancer.gov/statfacts/html/melan.html).
(O’Bryant CL et. al. Pharmacotherapy: A Pathophysiologic Approach [Internet]. 9ed. New York (NY): McGraw-Hill; c2015. Chapter 116. Melanoma; 2014 [cited 2016 Feb 28];
[Etiology and Epidemiology]; AccessPharmacy. Available from: http://accesspharmacy.mhmedical.com/content.aspx?bookid=689&Sectionid=48811511).
4. Pathophysiology
Melanocytes (epidermal & non-cutaneous)
Epidermal-dermal junctions of the skin,
choroid of the eye, meninges, digestive
tract, respiratory tract
Skin (most common)
Stages; can skip steps
No growth factors needed
PI3K-AKT pathway
(O’Bryant CL, et. al. Pharmacotherapy: A Pathophysiologic Approach [Internet]. 9ed. New York (NY): McGraw-Hill; c2015. Chapter 116. Melanoma; 2014 [cited 2016 Feb 28];
[Pathogenesis]; AccessPharmacy. Available from: http://accesspharmacy.mhmedical.com/content.aspx?bookid=689&Sectionid=48811511) .
5. Mutations
BRAF Mutation (MAPK) (higher
survival)
NRAS (lower survival)
c-KIT
CDKN2A
(O’Bryant CL, et. al. Pharmacotherapy: A Pathophysiologic Approach [Internet]. 9ed. New York (NY): McGraw-Hill; c2015. Chapter 116. Melanoma; 2014 [cited 2016 Feb 28];
[Etiology and Epidemiology]; AccessPharmacy. Available from: http://accesspharmacy.mhmedical.com/content.aspx?bookid=689&Sectionid=48811511).
6. Melanoma: Risk Factors
(The Skin Cancer Foundation. [Internet]. New York (NY). The Skin Cancer Foundation; c2016. Skin Cancer Facts; 2016 [updated 2016 Feb 5]. [about 5 screens]. Available from: http://www.skincancer.org/skin-cancer-
information/skin-cancer-facts#men/women/ ).
(O’Bryant CL, et. al. Pharmacotherapy: A Pathophysiologic Approach [Internet]. 9ed. New York (NY): McGraw-Hill; c2015. Chapter 116. Melanoma; 2014 [cited 2016 Feb 28]; [Etiology and Epidemiology]; AccessPharmacy.
Available from: http://accesspharmacy.mhmedical.com/content.aspx?bookid=689&Sectionid=48811511).
Genetic Risk Factors Environmental Risk Factors
Caucasian Melanocytic moles (number)
Light Hair Color Severe sunburns (blistering)
Family history High Intensity Sun Exposure
(Isolated)
Younger Men (Deaths) UV light <age 18 (UVB)
Immunocompromised Immunocompromised
Individual History of Cancer
7. Staging
T- Thickness of tumor
N- Number of Metastatic Nodes
M- Site of Tumor
Stage III: lymph node involvement
Stage IV: metastasis
(Urba WJ, et. al.Harrison's Principles of Internal Medicine [Internet]. 19 e New York (NY): McGraw-Hill; c2015. Chapter 105, Table 105-3, Staging Criteria for Melanoma. [cited 2016
Feb 28]. [Prognostic Factors]. Available from: http://accessmedicine.mhmedical.com/ViewLarge.aspx?figid=98709335 ).
(O’Bryant CL, Poust JC, DiPiro JT. Pharmacotherapy: A Pathophysiologic Approach [Internet]. 9ed. New York (NY): McGraw-Hill; c2015. Chapter 116. Table 116-3, Melanoma Tumor,
Node, Metastasis Classification; 2014 [cited 2016 Feb 28]. [Staging and Prognostic Factors]; AccessPharmacy. Available from:
http://accesspharmacy.mhmedical.com/ViewLarge.aspx?figid=48830564 ).
8. Clinical Presentation
Benign mole-------Dysplastic nevi --------
Melanoma lesion
Mid-region in men
Feet and legs in women
Warning Signs: Itchy, red, bleeding, swelling
Asymmetry, Border, Color, Diameter,
Enlargement/Evolution
Palpable lymph nodes
Diagnostic: SLNB, CMP, LDH
(O’Bryant CL, et. al. Pharmacotherapy: A Pathophysiologic Approach [Internet]. 9ed. New York (NY): McGraw-Hill; c2015. Chapter 116. Melanoma; 2014 [cited 2016 Feb 28]; [Clinical Presentation, Side Bar: Clinical
Presentation: General, Local Signs and Symptoms, Systemic Signs and Symptoms, Laboratory Tests, Other Diagnostic Tests]; AccessPharmacy. Available from:
http://accesspharmacy.mhmedical.com/content.aspx?bookid=689&Sectionid=48811511).
9. Patient case
JM is a 25 yo blonde Caucasian male. He reports to his friend who is a
pharmacist that he has had a mole on his back since he was a kid, but recently
that it has been changing color and bleeding. What should the pharmacist do?
A. Tell JM to ignore it, “it will go away.”
B. Tell JM that if he is worried about melanoma, there is a good prognosis for
people who have melanoma, and catch it in the early stages, so it a good idea
for him to go see his PCP for a definitive diagnosis.
C. Tell JM to use an emollient moisturizer, because it’s just dry skin.
D. Tell JM that he has a low prognosis of survival.
10. Standard of Treatment
(Stages III and IV)
Stage III after surgery
Interferon (IFN-Alpha2b)
Stage IV:
dacarbazine
temozolomide
ipilumumab
vemurafenib
T-VEC(O’Bryant CL, et. al. Pharmacotherapy: A Pathophysiologic Approach [Internet]. 9ed. New York (NY): McGraw-Hill; c2015. Chapter 116. Melanoma; 2014 [cited 2016 Feb 28]; [Treatment]; AccessPharmacy. Available from:
http://accesspharmacy.mhmedical.com/ViewLarge.aspx?figid=48830564 ).
(Shead DA, et. al. NCCN Guidelines for Patients: Melanoma Version 1 [Internet]. Fort Washington, PA: National Comprehensive Cancer Network Foundation; c2014 [cited 2016 Feb 29]. Chart 6, Systemic Therapy for advanced or metastatic melanoma [p. 83].
Available from: http://www.nccn.org/patients/guidelines/melanoma/#83/z ).
(Shead DA, Hanisch LJ, Marlow L, Ho M, McMillian N, Kidney S, Clarke R. NCCN Guidelines for Patients: Melanoma Version 1 [Internet]. Fort Washington, PA: National Comprehensive Cancer Network Foundation; c2014 [cited 2016 Feb 29]. Chart 5.3.2.,
Primary and Adjuvant Treatment [p. 64]. Available from: http://www.nccn.org/patients/guidelines/melanoma/#64/z ).
Lexicomp [Internet]. Hudson, Ohio: Wolters Kluwer. 2016. Lexi-Drugs: dacarbazine; [cited 2016 Feb 28]; [about 2 screens]. Available from: https://online.lexi.com/lco/action/doc/retrieve/docid/patch_f/6685
(Amgen.com. [Internet]. Thousand Oaks (CA). c2016. Imylgic Package Insert. 2016. [updated 2015 Oct] [cited 28 Feb 2016]; [page 1] Available from: http://pi.amgen.com/united_states/imlygic/imlygic_pi.pdf ).
11. Indication of T-VEC
T-VEC: Package Insert, “genetically modified
oncolytic viral therapy that is indicated for local
treatment of unresectable cutaneous, subcutaneous,
and nodal lesion patients with melanoma recurrent
after initial surgery.”
Package Insert, “Limitations of Use: Imylgic has not
been shown to improve overall survival or have an
effect on visceral metastases.”
https://media.licdn.com/mpr/mpr/AAEAAQAAAAAAAAaPAAAAJGExZ
TdlNmQzLTAzNGYtNDFkZi04NGIwLTU2ODBiODM5NDFiMg.jpg
(Amgen.com. [Internet]. Thousand Oaks (CA). c2016. Imylgic Package Insert. 2016. [updated 2015 Oct] [cited 28 Feb 2016]; [page 1] Available from:
http://pi.amgen.com/united_states/imlygic/imlygic_pi.pdf) .
12. (Lexicomp [Internet]. Hudson, Ohio: Wolters Kluwer. 2016. Lexi-Drugs: talimogene laherparepvec; [cited 2016 Feb 28]; [about 3 screens]. Available from: https://online.lexi.com/lco/action/doc/retrieve/docid/patch_f/5909571) .
Pharmacology of T-
VEC
Modified Herpes Simplex
Virus-1 (HSV-1) with two
proposed mechanisms of
action.
Selectivity Tumor cells
Site of Action Locally (Indication)
Strengths 1 million PFU/mL
100 million PFU/mL
Adverse effects Flu-like symptoms
Pain at injection site
T-VEC Summary
http://classroomclipart.com/images/gal
lery/Animations/Cartoons/virus_animati
on.gif
13. T-VEC Summary (Con’t)
Contraindications
Pregnancy or Immunocompromised
Who Should Use T-
VEC
Post-Surgery
(Labeled)
Mortality Overall Survival Not
Improved
Drug-Drug
Interactions
acyclovir
Company Amgen
(Lexicomp [Internet]. Hudson, Ohio: Wolters Kluwer. 2016. Lexi-Drugs: talimogene laherparepvec; [cited 2016 Feb 28]; [about 3 screens]. Available from: https://online.lexi.com/lco/action/doc/retrieve/docid/patch_f/5909571).
(Amgen.com. [Internet]. Thousand Oaks (CA). c2016. Imylgic Package Insert. 2016. [updated 2015 Oct] [cited 28 Feb 2016]; [page 1] Available from: http://pi.amgen.com/united_states/imlygic/imlygic_pi.pdf).
http://img.medscape.com/
news/2015/is_150430_mela
noma_needle_800x600.jpg
14. Follow-Up
JM saw his healthcare provider and Stage IV melanoma was confirmed. He has
recently had surgery, but the melanoma has come back, and this time it’s
inoperable. JM’s physician has suggested T-VEC. Which answer best describes the
role of T-VEC in the treatment of melanoma?
A. An injection administered in the earlier stages of melanoma
B. An injection administered by a healthcare provider that is indicated for use in
unresectable melanoma that is recurrent after surgery, that is generally used
in Stage III and IV melanoma, but is not the standard of treatment.
C. An injection that is first line therapy
D. An agent that is taken by the patient orally
(Lexicomp [Internet]. Hudson, Ohio: Wolters Kluwer. 2016. Lexi-Drugs: talimogene laherparepvec; [cited 2016 Feb 28]; [about 3 screens]. Available from:
https://online.lexi.com/lco/action/doc/retrieve/docid/patch_f/5909571).
(Amgen.com. [Internet]. Thousand Oaks (CA). c2016. Imylgic Package Insert. 2016. [updated 2015 Oct] [cited 28 Feb 2016]; [page 1] Available from:
http://pi.amgen.com/united_states/imlygic/imlygic_pi.pdf ).
15. Dosing
>5 cm < 4mL
>2.5 to 5 cm <2 mL
>1.5 to 2.5 cm <1 mL
> 0.5 to 1.5 cm <0.5 mL
<0.5 cm <0.1mL
Hepatic Impairment No adjustment
Renal Impairment No adjustment
(Lexicomp [Internet]. Hudson, Ohio: Wolters Kluwer. 2016. Lexi-Drugs: talimogene laherparepvec; [cited 2016 Feb 28]; [about 1 screens].
Available from: https://online.lexi.com/lco/action/doc/retrieve/docid/patch_f/5909571).
16. Administration
Route of
Administration
Injection
Site Tumor
Administered by Healthcare Providers
(Lexicomp [Internet]. Hudson, Ohio: Wolters Kluwer. 2016. Lexi-Drugs: talimogene laherparepvec; [cited 2016 Feb 28]; [about 2 screens]. Available from:
https://online.lexi.com/lco/action/doc/retrieve/docid/patch_f/5909571).
17. Storage
-90 to -70 degrees Celsius
Keep out of Light
Thaw vials as soon as
possible before
administration
Refrigerate
Do not refreeze
(Lexicomp [Internet]. Hudson, Ohio: Wolters Kluwer. 2016. Lexi-Drugs: talimogene laherparepvec; [cited 2016 Feb 28]; [about 2 screens]. Available from:
https://online.lexi.com/lco/action/doc/retrieve/docid/patch_f/5909571).
18. Clinical Trial 1: “Phase II Clinical Trial
of a Granulocyte-Macrophage Colony-
Stimulating Factor-Encoding, Second-
Generation Oncolytic Herpesvirus in
Patients with Unresectable Metastatic
Melanoma”
(Senzer NN, Kaufman HL, Amatruda T, Nemunaitis M, Reid T, Daniels G, Gonzalez R, Glaspy J, Whitman E, Harrington K, Goldsweig H, Marshall T, Love C, Coffin R, and Nemunaitis JJ. Phase II clinical trial of a granulocyte-macrophage colony-
stimulating factor-encoding, second generation oncolytic herpesvirus in patients with unresectable metastatic melanoma. J Clin Oncol. 2009 Dec 1; 27(34): 5763-5771).
19. Methods
Phase II Clinical Trial
No control group
Intent to Treat
50 patients:
10 patients Stage IIIC
40 patients Stage IV
January 2006- February 2008
74% non-surgical therapy
Funding: Gregory Daniels, Biovex
(Senzer NN, et. al. Phase II clinical trial of a granulocyte-macrophage colony-stimulating factor-encoding, second generation oncolytic herpesvirus in patients with unresectable metastatic melanoma. J Clin Oncol. 2009 Dec 1; 27(34):
5763-5771, Author’s Disclosures of Potential Conflicts of Interest (5771)).
20. Outcomes Measured
Primary Outcome:
Overall Response Rate
Complete Response + Partial Response
CT Scan
Secondary Outcomes:
Overall Survival
Safety
(Senzer NN, et. al. Phase II clinical trial of a granulocyte-macrophage colony-stimulating factor-encoding, second generation oncolytic herpesvirus in patients with unresectable metastatic melanoma. J Clin Oncol. 2009 Dec 1;
27(34): 5763-5771 (5764)).
21. Methods
(Senzer NN, et. al. Phase II clinical trial of a granulocyte-macrophage colony-stimulating factor-encoding, second generation oncolytic herpesvirus in patients with unresectable metastatic melanoma. J Clin Oncol. 2009
Dec 1; 27(34): 5763-5771 (5764)).
Inclusion Criteria Exclusion Criteria
Stage IIIc or IV melanoma Pregnant or lactating
Tumor apparent, but not operable Antivirals <14 days
Able to Inject Tumor Major Surgery < 14 days
Age >18 years old Participation in Clinical Trial < 1
month before entry
ECOG < 1 Bone Metastases
Life Expectancy > 4 months Tumor Swelling in areas that could
cause death
Recovery from prior therapy with > 4
weeks since chemotherapy or
radiotherapy
Autoimmune disease
Immunosuppressed
Adequate liver and renal function
22. Treatment Regimen
JS1/34.5-/47/granulocyte-macrophage colony stimulating factor:
HSV-1 (herpes simplex virus type 1)
Deleted ICP34.5- and ICP47
Treatment plan:
Initial: <4 mL of 106 pfu/mL
3 weeks later: 1 treatment of < 4 mL of 108 pfu/mL every 2
weeks for max of 24 treatments
(Non)-Compliant Patients: 1
(Senzer NN, et. al. Phase II clinical trial of a granulocyte-macrophage colony-stimulating factor-encoding, second generation oncolytic herpesvirus in patients with unresectable metastatic melanoma. J Clin Oncol. 2009 Dec
1; 27(34): 5763-5771 (5764, 5767)).
23. Methods: Statistical Analysis and
Other Analyses
Overall Response Rate: RECIST (Response
Evaluation Criteria of Solid Tumors)
Response Rate of the Patients: Two-Stage Simon
Design
Overall Survival Rates: Kaplan Meier Curve
Median Survival Rates: Kaplan Meier Curve
Safety Profile: National Cancer Institute Common
Technology Criteria of Adverse Events
(Senzer NN, et. al. Phase II clinical trial of a granulocyte-macrophage colony-stimulating factor-encoding, second generation oncolytic herpesvirus in patients with unresectable
metastatic melanoma. J Clin Oncol. 2009 Dec 1; 27(34): 5763-5771 (5764)).
24. Results: Baseline Characteristics
(Senzer NN, et. al. Phase II clinical trial of a granulocyte-macrophage colony-stimulating factor-encoding, second generation oncolytic herpesvirus in patients
with unresectable metastatic melanoma. J Clin Oncol. 2009 Dec 1; 27(34): 5763-5771, Table 1, Baseline Demographic and Clinical Characteristics, (5765)).
Baseline Characteristics
Number Percent
Male 22 44%
Female 28 56%
White 48 96%
Asian 1 2%
Hispanic 1 2%
IIIc 10 20%
IV 40 80%
IVM1a 16 32%
IVM1b 4 8%
IVM1c 20 40%
ECOG PS 1 31 62%
ECOG PS 0 19 38%
25. Results: Primary Endpoint & Follow-up
Overall Number of Patients 50
Partial Response: Number
of Patients
5
Complete Response:
Number of Patients
8
Overall Response Rate:
Number of Patients
13
Overall Response Percent
of Patients
26%
Median Follow-up 18 months
(Senzer NN, et. al. Phase II clinical trial of a granulocyte-macrophage colony-stimulating factor-encoding, second generation oncolytic herpesvirus in patients with unresectable metastatic melanoma. J Clin
Oncol. 2009 Dec 1; 27(34): 5763-5771, Table 2, Response Correlations, (5765)).
26. Results: Secondary Endpoint
(Senzer NN, et. al. Phase II clinical trial of a granulocyte-macrophage colony-stimulating factor-encoding, second generation oncolytic herpesvirus in patients with unresectable metastatic melanoma. J Clin Oncol. 2009 Dec 1; 27(34):
5763-5771, Figure 5, Kaplan Meier Curves (A) Survival Curves for all patients enrolled and those who achieved complete response (CR), partial response (PR), or surgical CR (sCR), (B) Survival Curves by Disease State, (5770)).
27. Adverse Effects (Safety)
Most common (3 or more patients):
Fever (52%)
Chills (48%)
Fatigue (32%)
Nausea (30%)
Vomiting (20%)
Headache (20%)
(Senzer NN, et. al. Phase II clinical trial of a granulocyte-macrophage colony-stimulating factor-encoding, second generation oncolytic herpesvirus in patients with unresectable metastatic melanoma. J Clin
Oncol. 2009 Dec 1; 27(34): 5763-5771 , Table 3, Safety Data (5767, 5770)).
28. Author’s Conclusions:
Overall Responses and safety
were shown in patients
Randomized, controlled
phase III study should be
performed
(Senzer NN, et. al. Phase II clinical trial of a granulocyte-macrophage colony-stimulating factor-encoding, second generation oncolytic herpesvirus in patients with unresectable metastatic melanoma. J Clin Oncol. 2009 Dec 1;
27(34): 5763-5771).
29. Strengths/Limitations
Strengths:
Intent to Treat
Variety of sub-stages
Limitations:
• Talked about Overall Survival Rate in
Conclusion
• Did not report p-values
• No discussion of how compliance measured
• Lack of racial diversity
• Overall Survival took into account Surgical
Response
• Unclear on modified RECIST criteria
(Senzer NN, et. al. Phase II clinical trial of a granulocyte-macrophage colony-stimulating factor-encoding, second generation oncolytic herpesvirus in patients with unresectable metastatic
melanoma. J Clin Oncol. 2009 Dec 1; 27(34): 5763-5771).
30. Clinical Trial 2: “Talimogene
Laherparevec Improves Durable
Response Rate in Patients with
Advanced Melanoma”
(Andtbacka R H.I., Kaufman HL, Collichio F, Amatruda T, Senzer N, Chesney J, Delman KA, Spitler LE, Puzanov I, Agarwala SS, Milhem M, Cranmer L, Curti B, Lewis K, Ross M, Guthrie T, Linette GP, Daniels GA, Harrington K, Middleton MR, Miller Jr. WH, Zager JS, Ye Y, Yao
B, Li Ai, Doleman S, VanderWalde A, Gansert J, and Coffin RS. Talimogene laherparepvec improves durable response rate in patients with advanced melanoma. J Clin Oncol. 2015 Sep 1; 33(25): 2780-2788).
31. Methods
Phase III Randomized Clinical Trial
Open-Label Study
May 2009- June 2011
Multi-national trial: U.S., Canada, South Africa
64 centers
Independent Monitoring Committee
Funding: Amgen, Takeda Pharmaceuticals, Viralytics
(Andtbacka R H.I. et. al.. Talimogene laherparepvec improves durable response rate in patients with advanced melanoma. J Clin Oncol. 2015 Sep 1; 33(25): 2780-2788, Authors’ Disclosures of Potential Conflict of
Interest (Authors’ Disclosures of Potential Conflict of Interests).
32. Methods
682 total patients screened
436 patients randomized
Treatment Regimen: T-VEC vs. GM-CSF
T-VEC: Initial: 106 pfu/mL; 3 weeks later: 108 pfu/mL; 2 weeks
later: 108 pfu/mL
GM-CSF: 125 micrograms/m2 once daily for 14 days in 28 day cycles
Primary Outcome: Durable Response Rate (DRR)
Secondary Outcomes: Overall Survival (OS), Overall Response Rate (ORR)
Median follow up: 44.4 months
(Andtbacka R H.I. et. al.. Talimogene laherparepvec improves durable response rate in patients with advanced melanoma. J Clin Oncol. 2015 Sep 1; 33(25): 2780-2788).
33. Methods: Patient Population
Screened: N= 682
(Andtbacka R H.I. et. al.. Talimogene laherparepvec improves durable response rate in patients with advanced melanoma. J Clin Oncol. 2015 Sep 1; 33(25): 2780-2788, Figure 1
Deposition of Patients, (2781)).
Did not undergo
random assignment:
n= 245
Randomly Assigned:
n= 436
Assigned to T-
VEC: n= 295
Assigned to
GM-CSF: n= 141
Discontinued:
Adverse Events: n= 3
Included in Efficacy Analysis: n=
295
Included in Safety Analysis: n= 292
Included in Efficacy Analysis: n=
141
Included in Safety Analysis: n= 127
Discontinued:
Adverse Events: n= 11
34. Methods: Statistical Analysis
95% power, 90% power for planned 430
patients in groups randomized at a 2:1 ratio
respectively
Two-sided alpha of 0.05
Intent to Treat: Fisher’s Exact Test
Per-Protocol Population: Fisher’s Exact Test
Overall Survival: unadjusted log-rank test
(Andtbacka R H.I. et. al.. Talimogene laherparepvec improves durable response rate in patients with advanced melanoma. J Clin Oncol. 2015 Sep 1; 33(25): 2780-2788 (2782)).
35. Inclusion/Exclusion Criteria Criteria
(Andtbacka R H.I. et. al.. Talimogene laherparepvec improves durable response rate in patients with advanced melanoma. J Clin Oncol. 2015 Sep 1; 33(25): 2780-2788, (2781)).
Inclusion Criteria Exclusion Criteria
Age > 18 Antiviral agents; intermittent or
chronic treatment
Confirmed tumor, not surgically
removable
High dose steroids
Stage IIIB-Stage IV melanoma Primary ocular melanoma
Injectable lesions Primary mucosal melanoma
LDH <1.5x the ULN Bone or Cerebral metastases
ECOG <1
39. Secondary Endpoint: Overall
Response Rate
Overall Response Rate over
95% CI
T-VEC: 21.4- 31.5 vs. GM-CSF:
1.9-9.5
P-Value<0.001
No Alpha Calculated
(Andtbacka R H.I. et. al.. Talimogene laherparepvec improves durable response rate in patients with advanced melanoma. J Clin Oncol. 2015 Sep 1; 33(25): 2780-2788, Table 2, Efficacy, (2783)).
40. Results: Overall Survival Rate
(Andtbacka R H.I., et. al. Talimogene laherparepvec improves durable response rate in patients with advanced melanoma. J Clin Oncol. 2015 Sep 1; 33(25): 2780-2788, Figure 4
Outcomes in Patient Subgroups, (2786)).
41. Results: Overall Survival Rate
(Andtbacka R H.I. et. al.. Talimogene laherparepvec improves durable response rate in patients with advanced melanoma. J Clin Oncol. 2015 Sep 1; 33(25): 2780-2788, Figure 4 Outcomes in Patient Subgroups,
(2786).)
42. Adverse Effects of T-VEC
Adverse Events Percentage of Events in
the T-VEC group
Percentage of Events in
the GM-CSF Group
Fatigue 50.3% 36.2%
Chills 48.6% 8.7%
Pyrexia 42.9% 8.7%
Nausea 35.6% 19.7%
Influenza-Like Illness 30.5% 15.0%
Injection Site Pain 27.7% 6.3%
Vomiting 21.2% 9.4%
Diarrhea 19.9% 10.2%
(Andtbacka R H.I. et. al.. Talimogene laherparepvec improves durable response rate in patients with advanced melanoma. J Clin Oncol. 2015 Sep 1; 33(25): 2780-2788, Table 3, Patient Incidence of AEs, (2787))
43. Author’s Conclusions
T-VEC improved DRR
T-VEC may help prevent
relapse or progression
New treatment option
(Andtbacka R H.I. et. al.. Talimogene laherparepvec improves durable response rate in patients with advanced melanoma. J Clin Oncol. 2015 Sep 1; 33(25): 2780-2788 (2787))
44. Strengths/Limitations
Strengths:
Randomized
Met Power
Multicenter
International Trial
Independent Monitoring
Committee
Intent to Treat
Variety of sub-stages
Limitations:
• ~67% of the patients
were in the T-VEC
treatment group
• Included some
patients with an
unknown ECOG and
LDH status
• Open-Label
(Andtbacka R H.I. et. al.. Talimogene laherparepvec improves durable response rate in patients with advanced melanoma. J Clin Oncol. 2015 Sep 1; 33(25): 2780-2788).
45. Student Conclusions
Phase II
Phase III: Efficacy and
Safety
Long-term effects
(Senzer NN, et. al. Phase II clinical trial of a granulocyte-macrophage colony-stimulating factor-encoding, second generation oncolytic herpesvirus in patients with unresectable metastatic melanoma. J Clin Oncol. 2009 Dec 1;
27(34): 5763-5771).
(Andtbacka R H.I. et. al.. Talimogene laherparepvec improves durable response rate in patients with advanced melanoma. J Clin Oncol. 2015 Sep 1; 33(25): 2780-2788).
47. References
O’Bryant CL, Poust JC, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, DiPiro JT. Pharmacotherapy: A Pathophysiologic Approach [Internet]. 9ed. New York (NY): McGraw-Hill; c2015.
Chapter 116. Melanoma; 2014 [cited 2016 Feb 28]; [Chapter 116]; AccessPharmacy. Available from: <http://accesspharmacy.mhmedical.com/content.aspx?bookid=689&Sectionid=48811511>.
Cancer.gov. [Internet]. Rockville, Maryland. National Cancer Institute. c2012. SEER Stat Facts Sheet: Melanoma of the Skin National Cancer Institute; 2012. [cited 28 Feb 2016]; [about 2
screens]. Available from: http://seer.cancer.gov/statfacts/html/melan.html
The Skin Cancer Foundation. [Internet]. New York (NY). The Skin Cancer Foundation; c2016. Skin Cancer Facts; 2016 [updated 2016 Feb 5]. [about 5 screens]. Available from:
http://www.skincancer.org/skin-cancer-information/skin-cancer-facts#men/women/
Urba WJ, Curti BD, Kasper D, Fauci A, Hauser S, Longo D, Jameson J, Loscalzo J. Harrison's Principles of Internal Medicine [Internet]. 19 e New York (NY): McGraw-Hill; c2015. Chapter 105,
Table 105-3, Cancer of the Skin. [cited 2016 Feb 28]. [Prognostic Factors]. Available from: http://accessmedicine.mhmedical.com/content.aspx?bookid=1130&Sectionid=79729820.
48. References (Con’t)
Shead DA, Hanisch LJ, Marlow L, Ho M, McMillian N, Kidney S, Clarke R. NCCN Guidelines for Patients: Melanoma Version 1 [Internet]. Fort Washington, PA:
National Comprehensive Cancer Network Foundation; 2014 [cited 2016 Feb 29]. Available from: http://www.nccn.org/patients/guidelines/melanoma/#1/z
Lexicomp [Internet]. Hudson, Ohio: Wolters Kluwer. 2016. Lexi-Drugs: dacarbazine; [cited 2016 Feb 28]; [about 3 screens]. Available from:
https://online.lexi.com/lco/action/doc/retrieve/docid/patch_f/5909571
Amgen.com. [Internet]. Thousand Oaks (CA). c2016. Imylgic Package Insert. 2016. [updated 2015 Oct] [cited 28 Feb 2016]; [page 1] Available from:
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