Partial response to erlotinib in a patient with imatinib-refractory sacral chordoma

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Abstract

Background

Chordoma is a rare, slow growing and locally aggressive mesenchymal neoplasm with uncommon distant metastases. It is a chemo-resistant disease with surgery and radiotherapy being the mainstay in treatment of localized disease. In advanced disease imatinib has a role. We report a case of metastatic sacral chordoma with symptomatic and radiological response to erlotinib post-progression on imatinib.

Case presentation

A 48-year-old male with a sacral chordoma underwent partial sacrectomy followed by post-operative radiotherapy. Upon recurrence he received palliative radiotherapy to hemipelvis and was offered therapy with imatinib. However, the disease was refractory to imatinib and he was started on treatment with erlotinib—showing a partial response on imaging at two months. He is currently doing well at 13 months since start of erlotinib.

Conclusions

As seen in previously reported cases, erlotinib is a therapeutic option in advanced chordoma, even in imatinib refractory cases and thus warrants exploration of its therapeutic role in prospective clinical trials.

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Most cited references 19

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Phase II study on lapatinib in advanced EGFR-positive chordoma.

S Stacchiotti, E Tamborini, S Lo Vullo … (2013)

To report on a prospective, investigator-driven, phase II study on lapatinib in epidermal growth factor receptor (EGFR)-positive advanced chordoma patients. From December 2009 to January 2012, 18 advanced progressing chordoma patients entered this study (median age: 61 years; disease extent: metastatic 72% and locally advanced 28%). Epidermal growth factor receptor (EGFR) expression and activation were evaluated by immunohistochemistry and/or phospho-arrays, real-time polimerase chain reaction, fluorescence immunostaining. Fluorescence in situ hybridization analysis was also carried out. Patients received lapatinib 1500 mg/day (mean dose intensity = 1282 mg/day), until progression or toxicity. The primary study end point was response rate (RR) as per Choi criteria. Secondary end points were RR by Response Evaluation Criteria in Solid Tumor (RECIST), overall survival, progression-free survival (PFS) and clinical benefit rate (CBR; RECIST complete response + partial response (PR) + stable disease (SD) ≥ 6 months). All patients were evaluable for response. Six (33.3%) patients had PR and 7 (38.9%) SD, as their best Choi responses, corresponding to RECIST SD in all cases. Median PFS by Choi was 6 [interquartile (IQ) range 3-8] months. Median PFS by RECIST was 8 (IQ range 4-12) months, with a 22% CBR. This phase II study showed a modest antitumor activity of lapatinib in chordoma. The clinical exploitation of EGFR targeting in chordoma needs to be further investigated, both clinically and preclinically. Clinical trial Registration No: EU Clinical Trials Register trial no. 2009-014456-29.

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CGP 57148, a tyrosine kinase inhibitor, inhibits the growth of cells expressing BCR-ABL, TEL-ABL, and TEL-PDGFR fusion proteins.

M. Carroll, S Ohno-Jones, S TAMURA … (1997)

CGP 57148 is a compound of the 2-phenylaminopyrimidine class that selectively inhibits the tyrosine kinase activity of the ABL and the platelet-derived growth factor receptor (PDGFR) protein tyrosine kinases. We previously showed that CGP 57148 selectively kills p210BCR-ABL-expressing cells. To extend these observations, we evaluated the ability of CGP 57148 to inhibit other activated ABL tyrosine kinases, including p185BCR-ABL and TEL-ABL. In cell-based assays of ABL tyrosine phosphorylation, inhibition of ABL kinase activity was observed at concentrations similar to that reported for p210BCR-ABL. Consistent with the in vitro profile of this compound, the growth of cells expressing activated ABL protein tyrosine kinases was inhibited in the absence of exogenous growth factor. Growth inhibition was also observed with a p185BCR-ABL-positive acute lymphocytic leukemia (ALL) cell line generated from a Philadelphia chromosome-positive ALL patient. As CGP 57148 inhibits the PDGFR kinase, we also showed that cells expressing an activated PDGFR tyrosine kinase, TEL-PDGFR, are sensitive to this compound. Thus, this compound may be useful for the treatment of a variety of BCR-ABL-positive leukemias and for treatment of the subset of chronic myelomonocytic leukemia patients with a TEL-PDGFR fusion protein.

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Sacral chordomas: Impact of high-dose proton/photon-beam radiation therapy combined with or without surgery for primary versus recurrent tumor.

Francis J. Hornicek, Henry J. Mankin, Nigel Delaney … (2006)

To assess the efficacy of definitive treatment of sacral chordoma by high-dose proton/photon-beam radiation therapy alone or combined with surgery. The records of 16 primary and 11 recurrent sacral chordoma patients treated from November 1982 to November 2002 by proton/photon radiation therapy alone (6 patients) or combined with surgery (21 patients) have been analyzed for local control, survival, and treatment-related morbidity. The outcome analysis is based on follow-up information as of 2005. Outcome results show a large difference in local failure rate between patients treated for primary and recurrent chordomas. Local control results by surgery and radiation were 12/14 vs. 1/7 for primary and recurrent lesions. For margin-positive patients, local control results were 10 of 11 and 0 of 5 in the primary and recurrent groups, respectively; the mean follow-up on these locally controlled patients was 8.8 years (4 at 10.3, 12.8, 17, and 21 years). Radiation alone was used in 6 patients, 4 of whom received > or =73.0 Gy (E); local control was observed in 3 of these 4 patients for 2.9, 4.9, and 7.6 years. These data indicate a high local control rate for surgical and radiation treatment of primary (12 of 14) as distinct from recurrent (1 of 7) sacral chordomas. Three of 4 chordomas treated by > or =73.0 Gy (E) of radiation alone had local control; 1 is at 91 months. This indicates that high-dose proton/photon therapy offers an effective treatment option.

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Author and article information

Contributors

Sameer Rastogi:

ORCID: http://orcid.org/0000-0003-4792-3083

samdoc_mamc@yahoo.com

Journal

Journal ID (nlm-ta): Clin Sarcoma Res

Journal ID (iso-abbrev): Clin Sarcoma Res

Title: Clinical Sarcoma Research

Publisher: BioMed Central (London )

ISSN (Electronic): 2045-3329

Publication date (Electronic): 12 December 2020

Publication date PMC-release: 12 December 2020

Publication date Collection: 2020

Volume: 10

Electronic Location Identifier: 28

Affiliations

[1 ]GRID grid.415237.6, ISNI 0000 0004 1767 8336, Department of Medical Oncology, , Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, ; New Delhi, India

[2 ]GRID grid.413618.9, ISNI 0000 0004 1767 6103, Department of Nuclear Medicine, , All India Institute of Medical Sciences, ; New Delhi, India

[3 ]GRID grid.413618.9, ISNI 0000 0004 1767 6103, Department of Pathology, , All India Institute of Medical Sciences, ; New Delhi, India

[4 ]GRID grid.413618.9, ISNI 0000 0004 1767 6103, Sarcoma Medical Oncology Clinic, All India Institute of Medical Sciences, ; New Delhi, India

Author information

Sameer Rastogi http://orcid.org/0000-0003-4792-3083

Article

Publisher ID: 149

DOI: 10.1186/s13569-020-00149-1

PMC ID: 7733273

SO-VID: c28d5a75-cf89-4184-aa13-22da67e0177a

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Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 9 June 2020

Date accepted : 3 December 2020

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ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: chordoma,egfr,erlotinib

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ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: chordoma, egfr, erlotinib

Partial response to erlotinib in a patient with imatinib-refractory sacral chordoma

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Abstract

Background

Case presentation

Conclusions

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Karger: Oncology

Most cited references 19

Phase II study on lapatinib in advanced EGFR-positive chordoma.

CGP 57148, a tyrosine kinase inhibitor, inhibits the growth of cells expressing BCR-ABL, TEL-ABL, and TEL-PDGFR fusion proteins.

Sacral chordomas: Impact of high-dose proton/photon-beam radiation therapy combined with or without surgery for primary versus recurrent tumor.

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