Precision Medicine in Osteosarcoma: MATCH Trial and Beyond
Abstract
:1. Introduction
2. Oncological Precision Medicine Trials
3. Osteosarcoma: The Challenges for Successful PMTs
3.1. Osteosarcoma: A Rare Tumour
3.2. Osteosarcoma: The Technical Issue of Dealing with Bones
3.3. Osteosarcoma: An Heterogenous Genomic Landscape
4. Target-Specific Clinical Trials for OS Patients
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
- Jafari, F.; Javdansirat, S.; Sanaie, S.; Naseri, A.; Shamekh, A.; Rostamzadeh, D.; Dolati, S. Osteosarcoma: A comprehensive review of management and treatment strategies. Ann. Diagn. Pathol. 2020, 49, 151654. [Google Scholar] [CrossRef] [PubMed]
- Bielack, S.S.; Hecker-Nolting, S.; Blattmann, C.; Kager, L. Advances in the management of osteosarcoma. F1000Ressearch 2016, 5, 2767. [Google Scholar] [CrossRef] [PubMed]
- Subbiah, V.; Wagner, M.J.; McGuire, M.F.; Sarwari, N.M.; Devarajan, E.; Lewis, V.O.; Westin, S.; Kato, S.; Brown, R.E.; Anderson, P. Personalized comprehensive molecular profiling of high risk osteosarcoma: Implications and limitations for precision medicine. Oncotarget 2015, 6, 40642–40654. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tirtei, E.; Asaftei, S.D.; Manicone, R.; Cesari, M.; Paioli, A.; Rocca, M.; Ferrari, S.; Fagioli, F. Survival after second and subsequent recurrences in osteosarcoma: A retrospective multicenter analysis. Tumori 2018, 104, 202–206. [Google Scholar] [CrossRef]
- Ferrari, S.; Briccoli, A.; Mercuri, M.; Bertoni, F.; Picci, P.; Tienghi, A.; del Prever, A.B.; Fagioli, F.; Comandone, A.; Bacci, G. Postrelapse survival in osteosarcoma of the extremities: Prognostic factors for long-term survival. J. Clin. Oncol. 2003, 21, 710–715. [Google Scholar] [CrossRef]
- Casali, P.G.; Bielack, S.; Abecassis, N.; Aro, H.T.; Bauer, S.; Biagini, R.; Bonvalot, S.; Boukovinas, I.; Bovee, J.V.M.G.; Brennan, B.; et al. Bone sarcomas: ESMO-PaedCan-EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann. Oncol. 2018, 29 (Suppl. 4), iv79–iv95. [Google Scholar] [CrossRef]
- Morganti, S.; Tarantino, P.; Ferraro, E.; D’Amico, P.; Duso, B.A.; Curigliano, G. Next Generation Sequencing (NGS): A Revolutionary Technology in Pharmacogenomics and Personalized Medicine in Cancer. Adv. Exp. Med. Biol. 2019, 1168, 9–30. [Google Scholar] [CrossRef]
- Tirtei, E.; Cereda, M.; De Luna, E.; Quarello, P.; Asaftei, S.D.; Fagioli, F. Omic approaches to pediatric bone sarcomas. Pediatr. Blood Cancer 2020, 67, e28072. [Google Scholar] [CrossRef]
- Zhao, J.; Dean, D.C.; Hornicek, F.J.; Yu, X.; Duan, Z. Emerging next-generation sequencing-based discoveries for targeted osteosarcoma therapy. Cancer Lett. 2020, 474, 158–167. [Google Scholar] [CrossRef]
- Parsons, D.W.; Roy, A.; Yang, Y.; Wang, T.; Scollon, S.; Bergstrom, K.; Kerstein, R.A.; Gutierrez, S.; Petersen, A.K.; Bavle, A.; et al. Diagnostic Yield of Clinical Tumor and Germline Whole-Exome Sequencing for Children with Solid Tumors. JAMA Oncol. 2016, 2, 616–624. [Google Scholar] [CrossRef]
- Vo, K.T.; Parsons, D.W.; Seibel, N.L. Precision Medicine in Pediatric Oncology. Surg. Oncol. Clin. N. Am. 2020, 29, 63–72. [Google Scholar] [CrossRef] [PubMed]
- Heymann, D. Metastatic osteosarcoma challenged by regorafenib. Lancet Oncol. 2019, 20, 12–14. [Google Scholar] [CrossRef]
- Egas-Bejar, D.; Anderson, P.M.; Agarwal, R.; Corrales-Medina, F.; Devarajan, E.; Huh, W.W.; Brown, R.E.; Subbiah, V. Theranostic Profiling for Actionable Aberrations in Advanced High Risk Osteosarcoma with Aggressive Biology Reveals High Molecular Diversity: The Human Fingerprint Hypothesis. Oncoscience 2014, 1, 167–179. [Google Scholar] [CrossRef] [PubMed]
- Allen, C.E.; Laetsch, T.W.; Mody, R.; Irwin, M.S.; Lim, M.S.; Adamson, P.C.; Seibel, N.L.; Parsons, D.W.; Cho, Y.J.; Janeway, K.; et al. Target and Agent Prioritization for the Children’s Oncology Group-National Cancer Institute Pediatric MATCH Trial. J. Natl. Cancer Inst. 2017, 109, djw274. [Google Scholar] [CrossRef] [Green Version]
- Coyne, G.O.; Takebe, N.; Chen, A.P. Defining precision: The precision medicine initiative trials NCI-MPACT and NCI-MATCH. Curr. Probl. Cancer 2017, 41, 182–193. [Google Scholar] [CrossRef] [PubMed]
- Mody, R.J.; Wu, Y.M.; Lonigro, R.J.; Cao, X.; Roychowdhury, S.; Vats, P.; Frank, K.M.; Prensner, J.R.; Asangani, I.; Palanisamy, N.; et al. Integrative Clinical Sequencing in the Management of Refractory or Relapsed Cancer in Youth. JAMA 2015, 314, 913–925. [Google Scholar] [CrossRef]
- Worst, B.C.; van Tilburg, C.M.; Balasubramanian, G.P.; Fiesel, P.; Witt, R.; Freitag, A.; Boudalil, M.; Previti, C.; Wolf, S.; Schmidt, S.; et al. Next-generation personalised medicine for high-risk paediatric cancer patients—The INFORM pilot study. Eur. J. Cancer 2016, 65, 91–101. [Google Scholar] [CrossRef] [Green Version]
- Van Tilburg, C.M.; Pfaff, E.; Pajtler, K.W.; Langenberg, K.P.; Fiesel, P.; Jones, B.C.; Balasubramanian, G.P.; Stark, S.; Johann, P.D.; Blattner-Johnson, M. The pediatric precision oncology study INFORM: Clinical outcome and benefit for molecular subgroups. J. Clin. Oncol. 2020, 38 (Suppl. 18), LBA10503. [Google Scholar] [CrossRef]
- Harttrampf, A.C.; Lacroix, L.; Deloger, M.; Deschamps, F.; Puget, S.; Auger, N.; Vielh, P.; Varlet, P.; Balogh, Z.; Abbou, S.; et al. Molecular Screening for Cancer Treatment Optimization (MOSCATO-01) in Pediatric Patients: A Single-Institutional Prospective Molecular Stratification Trial. Clin. Cancer Res. 2017, 23, 6101–6112. [Google Scholar] [CrossRef] [Green Version]
- Oberg, J.A.; Glade Bender, J.L.; Sulis, M.L.; Pendrick, D.; Sireci, A.N.; Hsiao, S.J.; Turk, A.T.; Dela Cruz, F.S.; Hibshoosh, H.; Remotti, H.; et al. Implementation of next generation sequencing into pediatric hematology-oncology practice: Moving beyond actionable alterations. Genome Med. 2016, 8, 133. [Google Scholar] [CrossRef] [Green Version]
- Harris, M.H.; DuBois, S.G.; Glade Bender, J.L.; Kim, A.; Crompton, B.D.; Parker, E.; Dumont, I.P.; Hong, A.L.; Guo, D.; Church, A.; et al. Multicenter Feasibility Study of Tumor Molecular Profiling to Inform Therapeutic Decisions in Advanced Pediatric Solid Tumors: The Individualized Cancer Therapy (iCat) Study. JAMA Oncol. 2016, 2, 608–615. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Chang, W.; Brohl, A.S.; Patidar, R.; Sindiri, S.; Shern, J.F.; Wei, J.S.; Song, Y.K.; Yohe, M.E.; Gryder, B.; Zhang, S.; et al. MultiDimensional ClinOmics for Precision Therapy of Children and Adolescent Young Adults with Relapsed and Refractory Cancer: A Report from the Center for Cancer Research. Clin. Cancer Res. 2016, 22, 3810–3820. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pincez, T.; Clément, N.; Lapouble, E.; Pierron, G.; Kamal, M.; Bieche, I.; Bernard, V.; Fréneaux, P.; Michon, J.; Orbach, D.; et al. Feasibility and clinical integration of molecular profiling for target identification in pediatric solid tumors. Pediatr. Blood Cancer 2017, 64, e26365. [Google Scholar] [CrossRef] [PubMed]
- Khater, F.; Vairy, S.; Langlois, S.; Dumoucel, S.; Sontag, T.; St-Onge, P.; Bittencourt, H.; Dal Soglio, D.; Champagne, J.; Duval, M.; et al. Molecular Profiling of Hard-to-Treat Childhood and Adolescent Cancers. JAMA Netw. Open. 2019, 2, e192906. [Google Scholar] [CrossRef] [PubMed]
- Groisberg, R.; Hong, D.S.; Holla, V.; Janku, F.; Piha-Paul, S.; Ravi, V.; Benjamin, R.; Kumar Patel, S.; Somaiah, N.; Conley, A.; et al. Clinical genomic profiling to identify actionable alterations for investigational therapies in patients with diverse sarcomas. Oncotarget 2017, 8, 39254–39267. [Google Scholar] [CrossRef] [PubMed]
- Flaherty, K.T.; Gray, R.J.; Chen, A.P.; Li, S.; McShane, L.M.; Patton, D.; Hamilton, S.R.; Williams, P.M.; Iafrate, A.J.; Sklar, J.; et al. Molecular Landscape and Actionable Alterations in a Genomically Guided Cancer Clinical Trial: National Cancer Institute Molecular Analysis for Therapy Choice (NCI-MATCH). J. Clin. Oncol. 2020, 38, 3883–3894. [Google Scholar] [CrossRef]
- Seligson, N.D.; Knepper, T.C.; Ragg, S.; Walko, C.M. Developing Drugs for Tissue-Agnostic Indications: A Paradigm Shift in Leveraging Cancer Biology for Precision Medicine. Clin. Pharmacol. Ther. 2020. [Google Scholar] [CrossRef]
- Gröbner, S.N.; Worst, B.C.; Weischenfeldt, J.; Buchhalter, I.; Kleinheinz, K.; Rudneva, V.A.; Johann, P.D.; Balasubramanian, G.P.; Segura-Wang, M.; Brabetz, S.; et al. The landscape of genomic alterations across childhood cancers. Nature 2018, 555, 321–327, Erratum in 2018, 559, E10. [Google Scholar] [CrossRef] [Green Version]
- Gianferante, D.M.; Mirabello, L.; Savage, S.A. Germline and somatic genetics of osteosarcoma—Connecting aetiology, biology and therapy. Nat. Rev. Endocrinol. 2017, 13, 480–491. [Google Scholar] [CrossRef]
- Lau, C.C.; Taylor, A.; Sun, M.J.Y.; Yu, A.; Shen, J.; Teot, L.; Barkauskus, D.; Krailo, M.; Gorlick, R.; Triche, T.; et al. Genomic Landscape of Osteosarcoma: A Target Report. In Proceedings of the The Connective Tissue Oncology Society (CTOS) Annual Meeting, Tokyo, Japan, 13–16 November 2019. Paper #01 3329872. [Google Scholar]
- Suehara, Y.; Alex, D.; Bowman, A.; Middha, S.; Zehir, A.; Chakravarty, D.; Wang, L.; Jour, G.; Nafa, K.; Hayashi, T.; et al. Clinical Genomic Sequencing of Pediatric and Adult Osteosarcoma Reveals Distinct Molecular Subsets with Potentially Targetable Alterations. Clin. Cancer Res. 2019, 25, 6346–6356. [Google Scholar] [CrossRef]
- Martin, J.W.; Squire, J.A.; Zielenska, M. The genetics of osteosarcoma. Sarcoma 2012, 2012, 627254. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Perry, J.A.; Kiezun, A.; Tonzi, P.; Van Allen, E.M.; Carter, S.L.; Baca, S.C.; Cowley, G.S.; Bhatt, A.S.; Rheinbay, E.; Pedamallu, C.S.; et al. Complementary genomic approaches highlight the PI3K/mTOR pathway as a common vulnerability in osteosarcoma. Proc. Natl. Acad. Sci. USA 2014, 111, E5564–E5573. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sayles, L.C.; Breese, M.R.; Koehne, A.L.; Leung, S.G.; Lee, A.G.; Liu, H.Y.; Spillinger, A.; Shah, A.T.; Tanasa, B.; Straessler, K.; et al. Genome-Informed Targeted Therapy for Osteosarcoma. Cancer Discov. 2019, 9, 46–63. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Roberts, R.D.; Lizardo, M.M.; Reed, D.R.; Hingorani, P.; Glover, J.; Allen-Rhoades, W.; Fan, T.; Khanna, C.; Sweet-Cordero, E.A.; Cash, T.; et al. Provocative questions in osteosarcoma basic and translational biology: A report from the Children’s Oncology Group. Cancer 2019, 125, 3514–3525. [Google Scholar] [CrossRef] [PubMed]
- Chen, X.; Bahrami, A.; Pappo, A.; Easton, J.; Dalton, J.; Hedlund, E.; Ellison, D.; Shurtleff, S.; Wu, G.; Wei, L.; et al. Recurrent somatic structural variations contribute to tumorigenesis in pediatric osteosarcoma. Cell Rep. 2014, 7, 104–112. [Google Scholar] [CrossRef] [Green Version]
- Tawbi, H.A.; Burgess, M.; Bolejack, V.; Van Tine, B.A.; Schuetze, S.M.; Hu, J.; D’Angelo, S.; Attia, S.; Riedel, R.F.; Priebat, D.A.; et al. Pembrolizumab in advanced soft-tissue sarcoma and bone sarcoma (SARC028): A multicentre, two-cohort, single-arm, open-label, phase 2 trial. Lancet Oncol. 2017, 18, 1493–1501, Erratum in 2017, 18, e711. [Google Scholar] [CrossRef]
- Keung, E.Z.; Burgess, M.; Salazar, R.; Parra, E.R.; Rodrigues-Canales, J.; Bolejack, V.; Van Tine, B.A.; Schuetze, S.M.; Attia, S.; Riedel, R.F.; et al. Correlative Analyses of the SARC028 Trial Reveal an Association Between Sarcoma-Associated Immune Infiltrate and Response to Pembrolizumab. Clin. Cancer Res. 2020, 26, 1258–1266. [Google Scholar] [CrossRef]
- Wu, C.C.; Beird, H.C.; Andrew Livingston, J.; Advani, S.; Mitra, A.; Cao, S.; Reuben, A.; Ingram, D.; Wang, W.L.; Ju, Z.; et al. Immuno-genomic landscape of osteosarcoma. Nat. Commun. 2020, 11, 1008. [Google Scholar] [CrossRef] [Green Version]
- Cathomas, R.; Rothermundt, C.; Bode, B.; Fuchs, B.; von Moos, R.; Schwitter, M. RANK ligand blockade with denosumab in combination with sorafenib in chemorefractory osteosarcoma: A possible step forward? Oncology 2015, 88, 257–260. [Google Scholar] [CrossRef] [Green Version]
- Zhou, Y.; Zhang, W.; Tang, F.; Luo, Y.; Min, L.; Zhang, W.; Shi, R.; Duan, H.; Tu, C. A case report of apatinib in treating osteosarcoma with pulmonary metastases. Medicine 2017, 96, e6578. [Google Scholar] [CrossRef]
- Glade Bender, J.; Verma, A.; Schiffman, J.D. Translating genomic discoveries to the clinic in pediatric oncology. Curr. Opin. Pediatr. 2015, 27, 34–43. [Google Scholar] [CrossRef] [PubMed]
- Zhou, Y.; Yang, D.; Yang, Q.; Lv, X.; Huang, W.; Zhou, Z.; Wang, Y.; Zhang, Z.; Yuan, T.; Ding, X.; et al. Single-cell RNA landscape of intratumoral heterogeneity and immunosuppressive microenvironment in advanced osteosarcoma. Nat. Commun. 2020, 11, 6322. [Google Scholar] [CrossRef] [PubMed]
Trial Title | Inclusion Criteria | N° Patients Enrolled/Analysed | N° Enrolled Patients with OS | N° Patients with One or More Actionable Alteration | N° Patients Treated with a Matched Therapy Based on Genomic Data | Ref. |
---|---|---|---|---|---|---|
Peds-MiOncoSeq | R/R tumours or rare tumours age: ≤22 yrs | 102/91 | 29 patients with sarcoma (unspecified) | 42 | 15 | [16] |
INFORM | R/R solid tumours age: <40 yrs | 57/52 | 4 OS | 39 * | 10 | [17] |
INFORM update 2020 | R/R solid tumours age: <40 yrs | 1300/525 | Not reported | 444 (120 pts with very high or high priority target) | 149 | [18] |
MOSCATO-01 | R/R solid tumours age: <25 yrs | 73/69 | 4 OS | 42 | 14 | [19] |
BASIC3 | paediatric tumours age: ≤18 yrs | 150/121 | 4 OS | 33 | Not reported | [10] |
PIPSeq | high-risk tumours age: ≤26 yrs | 107/101 | 6 OS + 5 other sarcoma not more defined | 38 | 6 | [20] |
iCat | R/R high-risk non-CNS solid tumours age: ≤30 yrs | 101/89 | 11 OS | 31 | 3 | [21] |
ClinOmics Program | non CNS solid tumours age: ≤25 yrs | 64/57 | 4 OS | 30 | Not reported ** | [22] |
MBB | High risk or R/R solid tumors age: ≤22 yrs | 60/58 | 4 OS | 23 | 6 | [23] |
TRICEPS | R/R or hard-to-treat tumours age: ≤22 yrs | 84/62 | 7 OS | 47 | 9 | [24] |
MD Anderson Program | R/R sarcoma age: 8–76 yrs | 102/102 | 11 OS | 95 | 14 (only 1 OS pt) | [25] |
NCI-MATCH Trial | R/R solid tumour, R/R lymphoma, R/R myeloma age: ≥18 yrs | 6391/5540 | 255 sarcomas not more defined | 31 | 21 | [26] |
Tumour Histotype | Age/Sex | Actionable Alteration Considered for Target-Therapy/Methods | Drugs Administered | Response | Ref. | |
---|---|---|---|---|---|---|
Patient 1 | Metastatic OS refractory to 3rd CT line | 21 yrs/female |
| Metformin + Rapamycine + Crizotinib | PD | [3] |
Patient 2 | Metastatic OS refractory to 4rd CT line | 16 yrs/male |
| Sorafenib + Bevacizumab + Temsirolimus (Phase I clinical trial NCT01187199) | PD | [3] |
Patient 3 | Localized OS refractory to 2nd CT line | 37 yrs/male |
| Sunitinib + Denosumab | SD after 18 months of treatment | [40] |
Patient 4 | Localized OS relapsed after 1st CT line | 50 yrs/male |
| Apatinib | PR at 11 months of treatment | [41] |
CHARACTERISTICS OF THE TRIALS (N° tot: 60 Clinical Trials Registered on clinicaltrials.gov) | N | % |
---|---|---|
INCLUSION CRITERIA | ||
TUMOUR HISTOLOGY | ||
Only Osteosarcoma | 14 | 23% |
Bone Sarcomas | 3 | 5% |
All type of sarcomas | 6 | 10% |
All solid tumour | 37 | 62% |
AGE OF ENROLLEMENT | ||
<12 years | 40 | 67% |
<25 years | 60 | 100% |
PHASE | ||
I | 16 | 27% |
II | 29 | 48% |
I/II | 13 | 22% |
IV | 2 | 3% |
RANDOMIZATION | ||
Yes | 9 | 15% |
No | 51 | 85% |
LINE OF THERAPY | ||
1st line | 5 | 8% |
2nd line and other | 49 | 82% |
Maintenance phase | 3 | 5% |
All lines of therapy | 3 | 5% |
TYPE OF INVESTIGATIONAL DRUG | ||
Target Therapy | 44 | 73% |
Non Target Therapy | 16 | 27% |
TYPE OF TARGET THERAPY | ||
Tyrosine kinase inhibitor | 11 * | 24% |
Monoclonal antibody | 8 * | 18% |
CAR-T | 6 | 13% |
CDK inhibitor | 5 | 11% |
mTOR inhibitor | 3 | 7% |
Combination of two target drugs | 4 | 9% |
Others | 8 | 18% |
TARGET THERAPY ASSOCIATED WITH CHEMOTHERAPY | ||
Yes | 16 | 36% |
No | 24 | 54% |
CAR-T conditioning regimen | 4 | 9% |
REQUESTED TARGET-ALTERATION FOR ENROLLMENT | ||
None | 42 | 70% |
IHC specific positive staining | 4 | 7% |
Specific genetic alteration | 14 | 23% |
AGE OF ENROLLEMENT | ||
<12 years | 40 | 67% |
<18 years | 56 | 93% |
>18 years | 60 | 100% |
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Tirtei, E.; Campello, A.; Asaftei, S.D.; Mareschi, K.; Cereda, M.; Fagioli, F. Precision Medicine in Osteosarcoma: MATCH Trial and Beyond. Cells 2021, 10, 281. https://doi.org/10.3390/cells10020281
Tirtei E, Campello A, Asaftei SD, Mareschi K, Cereda M, Fagioli F. Precision Medicine in Osteosarcoma: MATCH Trial and Beyond. Cells. 2021; 10(2):281. https://doi.org/10.3390/cells10020281
Chicago/Turabian StyleTirtei, Elisa, Anna Campello, Sebastian D. Asaftei, Katia Mareschi, Matteo Cereda, and Franca Fagioli. 2021. "Precision Medicine in Osteosarcoma: MATCH Trial and Beyond" Cells 10, no. 2: 281. https://doi.org/10.3390/cells10020281
APA StyleTirtei, E., Campello, A., Asaftei, S. D., Mareschi, K., Cereda, M., & Fagioli, F. (2021). Precision Medicine in Osteosarcoma: MATCH Trial and Beyond. Cells, 10(2), 281. https://doi.org/10.3390/cells10020281