Patient benefits

Learn how ROZLYTREK can benefit your patients

Select the tumour type you are interested in to learn more about how ROZLYTREK can benefit your patients.

Meet

Graham

Graham, a 55-year-old man, presented to his GP with marked shortness of breath which was restricting his daily activities (ECOG PS 2)

He had previously been active and had never smoked and further investigation was undertaken
A left lung adenocarcinoma was found, with involvement of supraclavicular lymph nodes and left pleural effusion
Graham was diagnosed with Stage IVA non-small cell lung cancer (T3aN3M1b) which had metastasised to the CNS

Question 1:

Would you perform molecular testing at this stage?

Not at this stage
Many different genetic alterations have been found in lung cancer cells.¹Molecular testing is recommended to characterise the type of lung cancer and identify targeted treatment options.²

Learn more about molecular testing

Initial treatment:

First-line chemotherapy with carboplatin + paclitaxel

Initial response followed by symptomatic and radiological progression
I would test selected targets (PD-L1, EGFR, ALK, ROS1, BRAF) via FISH/IHC

Although these targets represent the most common forms of lung cancer, several other molecular targets such as NTRK gene fusions are known to present somatic variants with therapeutic potential^3,4

Learn more about molecular testing

Testing with FISH/IHC did not reveal any clinically-relevant gene alterations
Yes, large-panel NGS testing

NGS has the high sensitivity, accuracy and throughput necessary to test for key therapeutic targets including all gene fusions.^2,5–10 Gene fusions have been reported in approximately 20% of all cancers and ESMO guidelines recommend testing all patients with metastatic NSCLC for ROS1 gene fusion.^11,12

Furthermore, NTRK is an evolving biomarker in NSCLC.¹²NTRK1–3 are rare oncogenic drivers occurring at low prevalence (< 1%) in a variety of tumours including NSCLC – typically in adenocarcinomas and never-smokers.¹²

NGS testing results:
NGS identified NTRK1-SQSTM1 fusion. Approximately 0.1–1% of NSCLC patients have NTRK gene fusions.¹³

Proceed to second question

Meet

Graham

Graham, a 55-year-old man, presented to his GP with marked shortness of breath which was restricting his daily activities (ECOG PS 2)

He had previously been active and had never smoked and further investigation was undertaken
A left lung adenocarcinoma was found, with involvement of supraclavicular lymph nodes and left pleural effusion
Graham was diagnosed with Stage IVA non-small cell lung cancer (T3aN3M1b) which had metastasised to the CNS

Show Patient Update

Graham has Stage IVA NSCLC with an NTRK1-SQSTM1 fusion which has metastasised to the CNS

Graham has recently reported difficulties with vision
A CT scan identifies brain metastases in the left occipital lobe¹⁴

CT scan of real patient before ROZLYTREK treatment

Close Patient Update

Brain image taken from a real patient pre-ROZLYTREK treatment, in: Drilon A, et al. Cancer Discov 2017;7:400–409.

Question 2:

Knowing the patient has CNS disease with an NTRK gene fusion, what treatment would you choose?

Further chemotherapy or radiotherapy for CNS metastasis along with systemic treatment

Treatment options for advanced/metastatic NSCLC include surgery, chemotherapy, radiation therapy, immunotherapy and targeted therapy.^3,4

A TRK inhibitor with proven CNS activity in patients with NTRK fusion+ solid tumours, such as ROZLYTREK, may be the most appropriate choice for this patient.^15,16

ROZLYTREK has shown activity in NTRK fusion+ NSCLC.³It is a potent, selective TRK inhibitor demonstrating antitumour activity within the CNS.¹⁵ ROZLYTREK crosses the blood–brain barrier to deliver a clinically meaningful response in patients with NTRK gene fusions and CNS metastasis.^15,16

Learn more about the efficacy of ROZLYTREK in NTRK fusion+ cancers
TRK inhibitor such as ROZLYTREK

ROZLYTREK is a potent, selective TRK inhibitor demonstrating antitumour activity within the CNS.¹⁵ ROZLYTREK crosses the blood–brain barrier to deliver a clinically meaningful response in patients with NTRK gene fusions and CNS metastasis.^15,16

Learn more about how ROZLYTREK can help your NTRK fusion+ patients

Meet

Heidi

Heidi is a 25-year-old primary teacher who has been experiencing bloody discharge from her left nipple for around 6 months

She went to speak to her GP about it, who instructed further tests
She had no family history of breast cancer
Sonography detected a 3 cm mass in her left breast (stage IIA)

Question 1:

Would you perform molecular testing at this stage?

Not at this stage

There is no clear consensus on the treatment of secretory breast cancer, but surgery seems to be the primary treatment currently.¹⁷

Surgery may be combined with chemotherapy and radiotherapy.¹⁷

Many different genetic alterations have been found in breast cancer cells.¹⁸ Molecular testing is recommended to characterise the type of breast cancer and identify targeted treatment options.¹⁹

Learn more about molecular testing
I would test selected targets (PD-L1 & BRCA1/2) via FISH/IHC
Testing with FISH/IHC did not reveal any clinically-relevant gene alterations

Although these targets represent common forms of breast cancer, several other molecular targets such as NTRK are known to present somatic variants with therapeutic potential¹

Furthermore, secretory breast carcinoma patients are usually:

Triple negative for HER2, ER, PR²⁰

Histological patterns including solid, microcystic, and tubular²¹

Targeted therapies including TRK inhibitors have shown activity in NTRK fusion+ breast cancers¹⁵
Yes, large-panel NGS testing

NGS testing results:
Molecular testing identified ETV6-NTRK3 gene fusion which was classified as a secretory breast carcinoma.

Secretory breast carcinoma is a rare condition that accounts for < 0.1% of all cases of invasive breast cancer.²²

NTRK fusions are found in more than 25 different cancers and are highly prevalent in secretory breast carcinoma (> 90%)²³

Molecular testing is recommended to characterise the type of breast cancer and identify targeted treatment options.¹⁹

NGS has the high sensitivity, accuracy and throughput necessary to test for key therapeutic targets, including all gene fusions.^18,24

Proceed to second question

Meet

Heidi

Heidi is a 25-year-old primary teacher who has been experiencing bloody discharge from her left nipple for around 6 months

She went to speak to her GP about it, who instructed further tests
She had no family history of breast cancer
Sonography detected a 3cm mass in her left breast (stage IIA)

Show Patient Update

Heidi has secretory breast carcinoma with an ETV6-NTRK3 fusion

Heidi had been worried about the breast secretions but had been embarrassed to go and see her doctor at first
Pathology findings revealed her tumour had characteristic morphology for secretory breast carcinoma:²⁵

Cell staining image for patient with secretory breast carcinoma

Close Patient Update

Immunohistochemical staining for S-100²⁵

Question 2:

Knowing the patient has CNS disease with an NTRK gene fusion, what treatment would you choose?

Further chemotherapy or radiotherapy

There is currently no consensus regarding treatment for secretory breast carcinoma, and treatment options may depend on the person's age and the size of the tumour.¹⁷ Options may include surgery to remove the tumour or mastectomy, surgery to also remove nearby lymph nodes, radiotherapy, and chemotherapy.¹⁷

A TRK inhibitor for patients with NTRK fusion+ secretory breast carcinoma, such as ROZLYTREK, may be the most appropriate choice for this patient.¹⁵

ROZLYTREK is a potent, selective TRK inhibitor, and delivers a clinically meaningful response in patients with NTRK gene fusions.¹⁵

Learn more about the efficacy of ROZLYTREK in NTRK fusion+ cancers
TRK inhibitor such as ROZLYTREK

ROZLYTREK is a potent, selective TRK inhibitor, and delivers a clinically meaningful response in patients with NTRK gene fusions.¹⁵

Learn more about how ROZLYTREK can help your NTRK fusion+ patients

Meet

Marcus

Marcus is a 48-year-old engineer who presented to his doctor with a palpable and painful lump on the left thigh

After instruction of an MRI and biopsy, the results suggested an undifferentiated sarcoma with a 6 cm resectable tumour – histologic grade G1, stage IB

Question 1:

Would you perform molecular testing at this stage?

Not at this stage

Initial treatment:
Surgery (wide excision with negative margins (R0) when possible) is the standard of care for sarcoma, associated with radiation therapy and chemotherapy.²⁶High-risk patients tend to relapse within 2–3 years.²⁶

Many different genetic alterations have been found in sarcoma cells.²⁷ Broad molecular testing to further characterise the tumour profile could support additional treatment options.²⁸

Learn more about molecular testing
I would test selected targets via FISH/IHC

Specific driver molecular abnormalities have been identified in up to 40% of soft tissue sarcomas,²⁹ with < 5% of sarcoma cases presenting with NTRK fusions.³⁰

Standard diagnosis of sarcoma consists of imaging assessments (MRI, CT or PET) and tissue biopsy to determine histological type, stage and resectability of the tumour.^26,31

Molecular testing is recommended to characterise the type of sarcoma and identify targeted treatment options, with immunohistochemistry being a valuable screening tool.³²

Targeted agents such as tyrosine kinase inhibitors are becoming important treatment options for soft tissue sarcomas.³³
Yes, large-panel NGS testing

NGS testing results:
Molecular testing identified an TPM3-NTRK1 gene fusion as soft tissue sarcoma.

p53, RB, PI3K and IDH gene mutations are the most prevalent mutations identified in sarcomas.³⁴

However, NTRK gene fusions are also oncogenic drivers in a variety of tumour types, including adult and paediatric sarcomas.³²

Molecular testing is recommended to characterise the type of sarcoma and identify targeted treatment options, and immunohistochemistry is a valuable screening tool.³²

Proceed to second question

Meet

Marcus

Marcus is a 48-year-old engineer who presented to his doctor with a palpable and painful lump on the left thigh

After instruction of an MRI and biopsy, the results suggested an undifferentiated sarcoma with a 6cm resectable tumour – histologic grade G1, stage IB

Show Patient Update

Marcus had been experiencing pain in his leg for a few months, which worsened when he was walking
Biopsy showed positivity for SMA and negative for CD31, CD34, desmin, keratins, S-100
Patient underwent primary resection, with subsequent progression in lung with multiple resectable lung metastases
He also had an episode of convulsions and a brain CT scan suggested resectable brain metastasis

Close Patient Update

MRI of mass in thigh³⁵

Image taken from here

Question 2:

Knowing the patient has CNS disease with an NTRK gene fusion, what treatment would you choose?

Further chemotherapy, radiotherapy and resection for metastasis

Chemotherapy, radiotherapy and, if possible, resection of metastases are the standard treatment options for advanced/metastatic soft tissue sarcoma.²⁶

However, targeted agents such as tyrosine kinase inhibitors are becoming important treatment options for soft tissue sarcomas.³³

A TRK inhibitor also with proven CNS activity in patients with NTRK fusion+ solid tumours, such as ROZLYTREK, may be the most appropriate choice for this patient.¹⁵

ROZLYTREK is a potent, selective TRK inhibitor demonstrating antitumour activity within the CNS.¹⁶ROZLYTREK crosses the blood-brain barrier to deliver a clinically meaningful response in patients with NTRK gene fusions and CNS metastasis.^15,16

Learn more about the efficacy of ROZLYTREK in NTRK fusion+ cancers
TRK inhibitor such as ROZLYTREK

TRK inhibitors provide effective treatment options for patients with sarcomas harboring NTRK gene fusions.³²

ROZLYTREK is a potent, selective TRK inhibitor demonstrating antitumour activity within the CNS.^15,16 ROZLYTREK crosses the blood-brain barrier to deliver a clinically meaningful response in patients with NTRK gene fusions and CNS metastasis.^15,16

Learn more about how ROZLYTREK can help your NTRK fusion+ patients

This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 4.8 of the SmPC for details on how to report adverse reactions.

Footnotes

ALK, anaplastic lymphoma kinase; BRCA, BReast CAncer gene; CD31/34, cluster of differentiation 31/34; CNS, central nervous system; CT, computed tomography; ECOG PS, Eastern Cooperative Oncology Group performance status; EGFR, epidermal growth factor receptor; ER, oestrogen receptor; FISH, fluorescence in situ hybridisation; HER, human epidermal growth factor receptor; HER2, human epidermal growth factor receptor 2; IDH, isocitrate dehydrogenase mutation; IHC, immunohistochemistry; MRI, magnetic resonance imaging; NGS, next-generation sequencing; NSCLC, non-small cell lung cancer; NTRK, neurotrophic tyrosine receptor kinase; PD-L1, programmed death-ligand 1; PET, positron emission tomography; PI3K, phosphoinositide 3-kinase; PR, progesterone receptor; RB, retinoblastoma; ROS1, c-ros oncogene 1; S-100, dysregulated S100 expression is a common feature in several human cancers; SMA, smooth muscle actin; TPM3, tropomyosin 3; TRK, tropomyosin receptor kinase.

References

Medline Plus. Genetics Home Reference. Lung Cancer. Available at: https://ghr.nlm.nih.gov/condition/lung-cancer#statistics (Accessed December 2020).
National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). Non-Small Lung Cancer. V.2.2021, December 16 2020. Available at: www.nccn.org/professionals/physician_gls/ (Accessed January 2020).
ESMO Guidelines. Advanced/metastatic NSCLC. Available at: https://www.esmo.org/guidelines/lung-and-chest-tumours/clinical-practice-living-guidelines-metastatic-non-small-cell-lung-cancer (Accessed December 2020).
Gregg JP, et al. Transl Lung Cancer Res 2019;8:286–301.
International Association for the Study of Lung Cancer. IASLC Atlas of ALK and ROS1 Testing in Lung Cancer. Available at: https://www.iaslc.org/research-education/publications-resources-guidelines/iaslc-atlas-alk-and-ros1-testing-lung-cancer (Accessed December 2020).
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Zheng Z, et al. Nat Med 2014;20:1479–1484.
Drilon A, et al. Clin Cancer Res 2015;21:3631–3639.
Grada A, et al, Invest Dermatol 2013;133:e11.
Vaishnavi A, Le AT, Doebele RC. Cancer Discov 2015;5:25–34.
Planchard D, et al. Ann Oncol 2018;29(Suppl 4):iv192–iv237.
Farago AF, et al. JCO Precis Oncol 2018;2018:PO.18.00037.
Drilon A, et al. Cancer Discov 2017;7:400–409.
ROZLYTREK Summary of Product Characteristics, 2020.
Doebele RC, et al. Efficacy and Safety of Entrectinib in Locally Advanced or Metastatic ROS1-Positive Non-Small Cell Lung Cancer (NSCLC). Poster presented at IASCLC 19^th World Conference on Lung Cancer; September 23–28, 2018; Toronto, Canada.
Malacards. Breast Secretory Carcinoma (SBC) Available at: https://www.malacards.org/card/breast_secretory_carcinoma (Accessed December 2020).
National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). Breast Cancer. V.6.2020, September 8 2020. Available at: https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf (Accessed December 2020).
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Krings G, et al. Modern Pathology 2017;30:1086–1099.
Li L, et al. Cancer Biol Med 2019;16(1):139–146.
Horowitz DP, et al. The Breast;2012:21(3):350–351.
Okamura R, et al. JCO Precis Oncol 2018;2018:PO.18.00183
Colomer R, et al. EClinicalMedicine 2020;25:100487.
Laé M, et al. Modern Pathology 2009;22:291–298.
Casali PG, et al. Anns Oncol 2018; 29 (Supplement 4): iv51–iv67.
Lucchesi C, et al. JAMA Oncol 2018;4(10):1398–1404.
Antonescu CR. Histopathology 2006;48(1):13–21.
Carmagnani Pestana R, et al. JCO Precis Oncol 2019;3:doi:10.1200/PO.12.00247.
Cocco E, et al. Nat Rev Clin Oncol 2018;15(12):731–747.
Smille, et al. EFFORT Open Rev 2017;2:421–431.
Demetri GD, et al. Ann Oncol 2020;S0923-7534(20)42297-5.
American Cancer Society. Targeted Drug Therapy for Soft Tissue Sarcoma. Available at: https://www.cancer.org/cancer/soft-tissue-sarcoma/treating/targeted-therapy.html (Accessed December 2020)
Gao P, et al. Ant-tum treat 2018;62:98–109.
Consult QD. Case study: Complex Resection of Soft Tissue Sarcoma. Available at: https://consultqd.clevelandclinic.org/case-study-complex-resection-of-soft-tissue-sarcoma/ (Accessed December 2020).