2012 EDUCATIONAL BOOK - American Society of Clinical Oncology

MANAGEMENT OF THYMIC CARCINOMA
Reference Therapy
Table 2. Selected Prospective and Larger Retrospective Series of Patients with Thymic Carcinoma Treated with
“Targeted” Therapies
exceptions, testing of targeted therapies in thymic carcinoma
has met with no significant success. Several prospective
trials of imatinib were launched after initial case
reports identified mutated KIT in patients with thymic
carcinoma and subsequent significant response to multitargeted
tyrosine kinase inhibitors. These studies included
patients with thymic carcinoma, sometimes requiring KIT
(or platelet-derived growth factor expression), but none
required the presence of KIT mutations for enrollment. In
the absence of patients with documented KIT mutations, no
patients had radiographic responses. Because of high epidermal
growth factor receptor (EGFR) expression in thymic
carcinoma, both gefitinib and erlotinib (with bevacizumab)
have been prospectively evaluated in a total of 14 patients
without radiographic response. No evidence of EGFR dependence
in thymic tumors has been reported (no EGFR mutations
and no significant focal EGFR gene amplification). One
targeted therapy has shown initial success in patients with
thymic carcinoma who were enrolled in a phase I trial. Two
of three patients with thymic carcinoma treated with PHA-
848125AC—a dual cyclin-dependent kinase 2/thropomyosin
receptor kinase A inhibitor—had radiographic responses
and long responses to therapy. This initial success has led to
Authors’ Disclosures of Potential Conflicts of Interest
Author
Employment or
Leadership
Positions
Prospective or
Retrospective Patients RR (%)
Consultant or
Advisory Role
Gregory J. Riely ARIAD;
Boehringer
Ingelheim;
Chugai Pharma;
Daiichi Sankyo;
Novartis;
Tragara
a multicenter phase II study of this drug in patients with
thymic carcinoma (clinicaltrials.gov NCT01011439).
Future Directions
The rarity of all thymic tumors, especially thymic carcinomas,
complicates prospective clinical research in these
diseases. As noted above, at sites with expertise in this
disease, the largest series of patients prospectively evaluated
was 23 and none of these studies has led to a breakthrough
in therapy for this disease. Given the uncommon
nature of thymoma and thymic carcinoma, empiric approaches
to drug evaluation conducted at a limited number
of centers are likely to be of little benefit. Under the
guidance of the ITMIG, researchers are developing a large
retrospective and prospective database to identify potential
improvements in care that can be derived from current
practices. In addition, ITMIG has put forth standards for
clinical research to allow comparison of clinical trial results
across groups. 17 Finally, the thymic cancer research community
needs to harness recent advances in sequencing technology
to vastly improve our understanding of the biology
of this disease to generate testable clinical research hypotheses.
Stock
Ownership Honoraria
Research
Funding
Bristol-Myers
Squibb
James Huang Bristol-Myers
Squibb
Andreas Rimner*
*No relevant relationships to disclose.
1. Girard N, Shen R, Guo T, et al. Comprehensive genomic analysis reveals
clinically relevant molecular distinctions between thymic carcinomas and
thymomas. Clin Cancer Res. 2009;15:6790-6799.
2. Girard N, Teruya-Feldstein J, Payabyab EC, et al. Insulin-like growth
factor-1 receptor expression in thymic malignancies. J Thorac Oncol. 2010;5:
1439-1446.
3. Zettl A, Strobel P, Wagner K, et al. Recurrent genetic aberrations in
thymoma and thymic carcinoma. Am J Pathol. 2000;157:257-266.
4. Huang J, Rizk NP, Travis WD, et al. Comparison of patterns of relapse
REFERENCES
Median PFS/TTP
(months)
Median OS
(months) Comment
26 Imatinib P 11 0 All patients were KIT� or PDGF� by IHC
27 Imatinib P 5 0 No patients had KIT mutations
28 Imatinib P 3 0 No patients had KIT mutations
29 Erlotinib, bevacizumab P 7 0
30 Gefitinib P 7 0
31 Belinostat P 16 0 3 12
32 Octreotide P 5 0 5 23
33 PHA 848125 P 3 67% Part of a phase I trial
Abbreviations: RR, recurrence rate; PFS, progression-free survival; TTP, time to progression; OS, overall survival; PDGF, platelet-derived growth factor receptor; IHC,
immunohistochemical.
Expert
Testimony
Other
Remuneration
in thymic carcinoma and thymoma. J Thorac Cardiovasc Surg. 2009;138:26-
31.
5. Chalabreysse L, Etienne-Mastroianni B, Adeleine P, et al. Thymic
carcinoma: A clinicopathological and immunohistological study of 19 cases.
Histopathology. 2004;44:367-374.
6. Takeda S, Sawabata N, Inoue M, et al. Thymic carcinoma. Clinical
institutional experience with 15 patients. Eur J Cardiothorac Surg. 2004;26:
401-406.
7. Huang J, Rizk NP, Travis WD, et al. Feasibility of multimodality
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