I sarcomi dei tessuti molli

(1)

Giacomo G. Baldi

Oncologia Medica “Sandro Pitigliani”

Nuovo Ospedale “S.Stefano”

Azienda USL Toscana centro Prato

Novità e sequenze terapeutiche nelle neoplasie ginecologiche,

melanoma e tumori rari:

I sarcomi dei tessuti molli

(2)

Fletcher CDM et al, WHO Classification 2013 Adipocytic tumours

Well deifferentiated / dedifferentiated liposarcoma Myxoid / round cell liposarcoma

Pleomorphic liposarcoma Fibroblastic / myofibroblastic tumours

Fibromatosis (desmoid) DFSP

Solitary fibrous tumour / haemangiopericytoma IMT

Low grade myofibroblastic sarcoma Infantile fibrosarcoma

Adult fibrosarcoma Mixofibrosarcoma SEF

LGFMS

Smooth muscle tumours Leiomyosarcoma Skeletal muscle tumours

Embryonal rhabdomyosarcoma Alveolar rhabdomyosarcoma Pleomorphic rhabdomyosarcoma Vascular tumours

Epithelioid haemangioendothelioma Angiosarcoma of soft tissue

GIST

Nerve sheath tumors MPNST Malignant GCT Chondro-osseous tumours

Mesenchymal chondrosarcoma Extraskeletal osteosarcoma Tumours of uncertain differentiation

Synovial sarcoma Epithelioid sarcoma Alveolar soft part sarcoma Clear cell sarcoma of soft tissue Extraskeletal myxoid chondrosarcoma Extraskeletal Ewing sarcoma

Desmoplastic small round cell tumour Extra-renal rhabdoid tumour

Malignant mesenchymoma Malignant PEComa

Intimal sarcoma

(3)

Soft tissue sarcoma

Courtesy A.P. Dei Tos

(4)

Soft tissue sarcoma

# 1463 pts

• Full  56%

• Partial  35%

• Zero  8%

Ray-Coquard I et al, Ann Oncol 2012

(5)

Soft tissue sarcoma: localised disease…

Soft tissue sarcoma-high risk-primary and localised disease completely resected/resectable

standard: surgery +/- RT

(neo) adjuvant systemic treatment to increase the chance of cure

(6)

Pervaiz et al, Cancer 2008

5-10% absolute improvement in OS

(7)

# 351 pts

• Median FUP 8 yrs

• Adm 75 mg/sqm + Ifo 5 g/sqm

• G2 and G3 (46%)

• Any histology (90 pts other histo)

Woll et al, Lancet Oncol 2012

(8)

Frustaci et al, J Clin Oncol 2001

epiADM 120 mg/sqm + IFX 9 g/sqm q 21 days

Gronchi et al, J Clin Oncol 2012

(9)

Gronchi et al, Lancet Oncol 2017

(10)

Median FUP 12.6 months

(11)

Weaknesses

• One-sided significance test

• No control arm

• Short median follow-up (12.6 months)

Actions taken

• Amendment to two-sided significance test

• Final analysis awaited

Strengths

• Significance both in DFS and OS

• Size of the effect

• Persistent difference in DFS in 2 indipendent sets of observations

• Effect on DM free survival

(12)

Longer FU is needed but the shape of the curve of the standard arm is superimposable to the previous study

(13)

(Neo) adjuvant chemotherapy not standard High risk

Waiting for the final analysis of the STS-ISG 10-01 study

(14)

Soft tissue sarcoma: advanced disease…

Tap et al, Lancet 2016

(15)

(16)

(17)

Weaknesses

• Unknown mechanisms of actions

• Discrepancy between PFS and OS improvement

• Limited number of patients

Actions taken

• Phase 1b study ongoing in potentially resectable patients

• Phase 1 study ongoing olara plus doxorubicin and ifosfamide vs doxorubicin and ifosfamide

• Phase 3 study completed, results awaited

Strengths

• First study showing a improvement in OS

• Magnitude of improvement

(18)

Novel standard?

Patient selection (need for tumor shrinkage, histology)

Doxorubicin: 8 cycles? (75 mg/smq = 600 mg/smq)

Cardioxane administration (off label)

(19)

Soft tissue sarcoma: advanced disease…further line

Schöffski et al, Lancet 2016

(20)

(21)

(22)

X

Demetri et al, J Clin Oncol 2017

(23)

Demetri et al, J Clin Oncol 2017

(24)

Progressive WD/DD retroperitoneal LPS

4^th line…

Eribulin X 3

(25)

Soft tissue sarcoma: what future?

Frezza et al, BMC Med 2017

(26)

Phase I-II trial of sunitinib plus nivolumab after standard treatment

in advanced soft tissue and bone sarcomas

Main inclusion criteria

 Histologic diagnosis of soft tissue sarcoma (undifferentiated pleomorphic sarcoma, synovial sarcoma, alveolar soft part sarcoma, clear cell sarcoma, angiosarcoma, epithelioid hemangiosarcoma, solitary fibrous tumor and epithelioid sarcomas) or bone sarcoma (osteosarcoma/high grade bone sarcoma, Ewing sarcoma or dedifferentiated chondrosarcoma)

 Pathology specimens available for centralized review

 ECOG PS <=2

Patients have previously received at least anthracyclines Main exclusion criteria

Three or more previous lines of chemotherapy for the advanced disease

Soft tissue sarcoma: what future?

(27)

Soft tissue sarcoma: conclusions

 Sarcomas are heterogeneous

 Accurate diagnosis is a challenge

 Referral to expert rare cancer pathologist

 Multidisciplinar approach in referral institutions

(28)

Networks are the best tool for proper referral

(29)

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