Progress in Rare Cancers Is ASCO Advance of the Year

Zosia Chustecka

February 04, 2019

Advances in the treatment of rare cancers have been chosen as the clinical cancer advances of the year by the American Society of Clinical Oncology (ASCO).

ASCO's annual report on progress against cancer, issued for the 14th consecutive year, was published online January 31 in the Journal of Clinical Oncology. The report covers the period from November 2017 through October 2018.

The report highlights five studies that show "significant steps forward" in the treatment of rare cancers, which together account for about 20% of all cancers diagnosed in the United States.

The five advances in rare cancers highlighted in the report were as follows:

  • Targeted therapy for anaplastic thyroid carcinomas (ATCs). This is a rare type of thyroid cancer, accounting for fewer than 2% of cases. It is associated with a worse prognosis than more common forms of thyroid cancer. In 2018, the US Food and Drug Administration approved a new treatment for ATC for the first time in 50 years. The agent, for use in the treatment of BRAF-mutated ATC, consists of a combination of the targeted therapies the BRAF inhibitor dabrafenib (Tafinlar, Novartis) and the MEK inhibitor trametinib (Mekinist, Novartis). The approval was based on results from a single-arm phase 2 trial in 16 patients with BRAF-mutated tumors, all of whom had received prior radiotherapy, surgery, and/or chemotherapy. Of these patients, 69% responded to the drug combination, and at the time of publication, nearly half (seven patients) had experienced ongoing responses (J Clin Oncol. 2018;36:7-13).

  • Sorafenib benefit in desmoid tumor. This rare type of sarcoma, which can regress spontaneously, was previously treated with off-label products. In what was hailed as a landmark study, investigators conducted a global, phase 3 trial in 87 patients with unresectable progressive desmoid tumors. The rate for 2-year progression-free survival (PFS) was 87% among patients who received the tyrosine kinase inhibitor sorafenib (Nexavar, Bayer), compared to 43% for those taking placebo (N Engl J Med. 2018;379:2417-2428).

  • Radiolabeled drug benefit in midgut neuroendocrine tumors (NETs). This is a rare cancer, thought to affect fewer than 3 per 100,000 people annually. It is usually treated with somatostatin or octreotide (Sandostatin, Novartis), a synthetic long-lasting form of somatostatin. The advance is with the product lutetium dotatate Lu-177 (Lutathera, Advanced Accelerator Applications), which was approved by the FDA in January 2018 and consists of octreotide to which is attached the radioisotope 177Lu. In the phase 3 NETTER-1 trial, conducted in 229 patients with midgut NET, the estimated PFS after 20 months was 65.2% in the lutetium dotatate Lu-177 group and 10.8% in the octreotide group (N Engl J Med. 376:125-135, 2017). An interim analysis suggested a longer overall survival; there were 14 deaths among patients taking the novel drug, compared with 26 deaths among patients taking octreotide. A follow-up analysis showed important quality-of-life benefits, with a longer period of overall better health (28.8 months vs 6.1 months) and better physical functioning (25.2 months vs 11.5 months) (J Clin Oncol. 2018;36:2578-2584).

  • Trastuzumab for uterine serous carcinoma. This is a rare form of endometrial cancer that accounts for about 10% of cases but around 40% of recurrences and deaths. About 30% of uterine serous carcinomas overexpress the HER2 gene. The HER2-targeted agent trastuzumab (Herceptin, Roche/Genentech) is used primarily for women with HER2-positive breast cancer. In a phase 2 trial involving 61 women with advanced or recurrent uterine serous carcinoma who overexpressed HER2/neu, patients were treated with either chemotherapy (carboplatin plus paclitaxel) alone or with chemotherapy plus trastuzumab. The addition of trastuzumab improved the median time to disease progression to 12.6 months, compared to 8 months for patients who received chemotherapy alone (J Clin Oncol. 2018;36:2044-2051).

  • Pexidartinib for tenosynovial giant cell tumors. These rare, debilitating tumors, which are generally found in younger, working-age adults, frequently affect physical ability and cause severe loss of function. There is no standard therapy; the usual management is surgery, with multiple synovectomies and even joint replacements. The novel drug pexidartinib (Daiichi Sankyo) acts as an inhibitor of colony stimulating factor–1 receptor and has shown some promise, although it is not currently available. In the ENLIVEN trial, which involved 122 patients, the drug yielded an overall response rate of 39%, compared with 0% for patients receiving placebo. Patients taking pexidartinib showed a statistically significant improvement in pain scores, range of motion, and physical function compared to those taking placebo (J Clin Oncol. 2018;36_suppl.11502). However, serious liver toxicity occurred in some patients, and a study is underway to examine these safety concerns, the ASCO report notes.

The report also highlights a number of other clinical cancer advances, including progress made in the past year with immunotherapy in various cancer types, as well as a promising potential cancer diagnostic tests, dubbed CANCERSEEK. Most of the advances highlighted in the report have been reported in detail by Medscape Medical News.

J Clin Oncol. Published online January 19. 2019. Full text

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