An update on clinical oncology for the non-oncologist

Kaliks, Rafael Aliosha

doi:10.1590/S1679-45082016MD3550

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Sumário

Medical Developments • Einstein (São Paulo) 14 (2) • Apr-Jun 2016 • https://doi.org/10.1590/S1679-45082016MD3550 copy

An update on clinical oncology for the non-oncologist

Authorship SCIMAGO INSTITUTIONS RANKINGS

ABSTRACT

Recent advances in the understanding of tumor driver mutations, signaling pathways that lead to tumor progression, and the better understanding of the interaction between tumor cells and the immune system are revolutionizing cancer treatment. The pace at which new treatments are approved and the prices at which they are set have made it even more difficult to offer these treatments in countries like Brazil. In this review we present for the non-oncologist these new treatments and compare their availability in Brazilian public health system and private health system with that of developed countries.

Neoplasms/trends; Immunotherapy/trends

Reference	Tumor type (by organ)	Name of drug	Mechanism of action	Indication	Main results	Availability in Brazil
Verma et al.⁽⁴⁾	Breast	Ado-trastuzumab emtansine (T-DM1)	Antibody-drug conjugate against Her2+ cells	Metastatic Her2+ breast cancer, after failing trastuzumab and taxane	Improved PFS and overall survival compared with lapatinib and capecitabine	Registered in Brazil. Not available in Brazilian Public Health System
Swain et al.⁽⁵⁾	Breast	Pertuzumab	Her2 inhibition	Metastatic Her2+ breast cancer	Improved PFS and overall survival compared with trastuzumab and taxane	Registered in Brazil. Not available in Brazilian Public Health System
Piccart et al.⁽⁶⁾	Breast	Everolimus	mTOR inhibitor	Metastatic HR+ and Her2- breast cancer in combination with exemestane	Improved PFS compared with second line exemestane alone	Registered in Brazil. Not available in Brazilian Public Health System
Turner et al.⁽⁷⁾	Breast	Palbociclib	CDK4 and CDK6 inhibitor	Metastatic HR+ and Her2- breast cancer in combination with fulvestrant	Improved PFS compared with second line Fulvestrant alone	Not registered in Brazil
Tewari et al.⁽⁸⁾	Cervix	Bevacizumab	VEGF inhibitor	Metastatic cervical cancer	Improved overall survival when added to chemotherapy	Registered in Brazil. Not available in the Brazilian Public Health System
Grothey et al.⁽⁹⁾	Colorectal	Regorafenib	Multikinase inhibitor	Previously treated metastatic colorectal cancer	Modest improvement in overall survival compared with supportive care alone	Not registered in Brazil
Fuchs et al.⁽¹⁰⁾	Gastric	Ramucirumab	VEGFR2 antagonist	Inoperable gastric or gastroesophageal junction adenocarcinoma after prior chemotherapy	Improved survival compared with placebo	Not registered in Brazil
Demetri et al.⁽¹¹⁾	GIST	Regorafenib	Multikinase inhibitor	Metastatic GIST after standard treatment with imatinib and sunitinib	Improved PFS compared with placebo	Not registered in Brazil
Wu et al.⁽¹²⁾; Sequist et al.⁽¹³⁾	Lung	Afatinib	EGFR inhibitor	Metastatic NSCLC with EGFR exon 19 deletion or L858R EGFR mutation	Improved PFS compared with gemcitabine and cisplatin or with cisplatin and pemetrexed	Not registered in Brazil
Shaw et al.^(14,15)	Lung	Crizotinib	ALK inhibitor, ROS1 inhibitor	Metastatic NSCLC with ALK-EML4 fusion, or with ROS1 rearrangement	Improved PFS compared with pemetrexed in platinum refractory disease	Not registered in Brazil
Shaw et al.⁽¹⁶⁾	Lung	Ceritinib	ALK inhibitor	Metastatic ALK-rearranged NSCLC	Responses in naïve and crizotinib pretreated disease	Not registered in Brazil
Chapman et al.⁽¹⁷⁾	Melanoma	Vemurafenib	BRAF inhibitor	Metastatic melanoma with BRAF V600E mutation	Improved overall survival and PFS compared with Dacarbazine	Registered in Brazil. Not available in the Brazilian Public Health System
Robert et al.⁽¹⁸⁾	Melanoma	Dabrafenib	BRAF inhibitor	Metastatic melanoma BRAF V600E mutation	Improved overall survival when combined with Trametinib, compared with Vemurafenib	Not registered in Brazil.
Robert et al.⁽¹⁸⁾	Melanoma	Trametinib	MEK inhibitor	Metastatic Melanoma with BRAF V600E or V600K mutation	Improved overall survival when combined with Dabrafenib, compared with Vemurafenib	Not registered in Brazil
Ledermann et al.⁽¹⁹⁾	Ovary	Olaparib	Inhibitor of poly (ADP-ribose) polymerase	BRCA mutated advanced ovarian cancer	Improved PFS compared with placebo in platinum sensitive relapse	Not registered in Brazil
Brose et al.⁽²⁰⁾	Thyroid	Sorafenib	Multi-kinase inhibitor	Metastatic differentiated thyroid cancer refractory to radioactive iodine	Improved PFS compared with placebo	Not registered in Brazil for this indication
Schlumberger et al.⁽²¹⁾	Thyroid	Lenvatinib	VEGF receptor inhibitor, PDGFR inhibitor, RET and KIT	Metastatic differentiated thyroid cancer refractory to radioactive iodine	Improved PFS compared with placebo	Not registered in Brazil
Elisei et al.⁽²²⁾	Medullary thyroid	Cabozantinib	MET, VEGFR2 and RET inhibitor	Progressive metastatic medullary thyroid cancer	Improved PFS compared with placebo	Not registered in Brazil
Wells et al.⁽²³⁾	Medullary thyroid	Vandetanib	RET kinase inhibitor and VEGF inhibitor	Progressive metastatic medullary thyroid cancer	Improved PFS compared with placebo	Not registered in Brazil

Reference	Tumor type (by organ)	Name of drug	Mechanism of action	Indication	Main results	Availability in Brazil
Hodi et al.⁽²⁵⁾; Robert et al.⁽²⁶⁾	Melanoma	Ipilimumab	Anti-CTLA-4	Metastatic melanoma	Improved overall survival compared with gp100 vaccine and improved overall survival when added to dacarbazine compared with dacarbazine alone	Registered in Brazil. Not available in the Brazilian Public Health System
Robert et al.⁽²⁷⁾ e Weber et al.⁽²⁸⁾	Melanoma	Nivolumab	Anti-PD1	Metastatic melanoma without BRAF mutation or after progression on Ipilimumab and BRAF inhibitor	Improved overall survival and progression free survival compared with dacarbazine	Not registered in Brazil
Robert et al.⁽²⁹⁾	Melanoma	Pembrolizumab	Anti-PD1	Metastatic melanoma	Improved overall survival and progression free survival compared with ipilimumab	Not registered in Brazil
Brahmer et al.⁽³⁰⁾	Lung	Nivolumab	Anti-PD1	Metastatic NSCLC, squamous histology	Improved overall survival, progression free survival and response rate compared with Docetaxel	Not registered in Brazil
Garon et al.⁽³¹⁾	Lung	Pembrolizumab	Anti-PD1	Metastatic NSCLC	Significant antitumor activity	Not registered in Brazil

Reference	Tumor type (by organ)	Name of drug	Mechanism of action	Indication	Main results	Availability in Brazil
Ryan et al.⁽³⁹⁾	Prostate	Abiraterone	Blocks cytochrome P450 17 alpha-hydroxilase reducing androgen production	Metastatic castration resistant prostate cancer	Improvement in overall survival compared with prednisone	Registered in Brazil. Not available in the Brazilian Public Health System
Beer et al.⁽⁴⁰⁾	Prostate	Enzalutamide	Androgen receptor blocker and androgen receptor signal inhibitor	Metastatic Castration resistant prostate cancer	Improvement in overall survival compared with placebo	Registered in Brazil for castration and chemotherapy refractory disease. Not available in Brazilian Public Health System
Sweeney et al.⁽⁴¹⁾; James et al.⁽⁴²⁾	Prostate	Docetaxel	Interferes with mitotic spindle	Upfront treatment of castration sensitive metastatic prostate cancer	Improvement in overall survival when added to castration, compared with castration alone	Registered in Brazil. Available in the Brazilian Public Health System
Parker et al.⁽⁴³⁾	Prostate	Rad 223 dichloride	Alpha emitter that targets bone metastases	Metastatic (to the bones) castration resistant prostate cancer	Improved overall survival compared with placebo	Registered in Brazil. Not available in the Brazilian Public Health System
Cortes et al.⁽⁴⁴⁾	Breast	Eribulin mesilate	Microtubule inhibitor	Previously treated metastatic breast cancer	Improved overall survival compared with treatment of physicians choice	Registered in Brazil. Not available in the Brazilian Public Health System

Instituto Israelita de Ensino e Pesquisa Albert Einstein Avenida Albert Einstein, 627/701 , 05651-901 São Paulo - SP, Tel.: (55 11) 2151 0904 - São Paulo - SP - Brazil
E-mail: revista@einstein.br

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[1] Corresponding author
: Rafael Aliosha Kaliks – Avenida Albert Einstein, 627/701 – Morumbi – Zip code: 05652-900 – São Paulo, SP, Brazil – Phone: (55 11) 2151-1648 – E-mail: rkaliks@einstein.br