希少脳腫瘍治療を変化させる可能性(Abstract LBA2000)

術後補助化学療法は1p/19q co-deletionのない退形成性神経膠腫患者の予後を改善する

Adjuvant chemotherapy improves outcomes for patients with anaplastic glioma without 1p/19q co-deletion

2016年American Society of Clinical Oncology年次集会で発表された第III相試験の早期結果から、標準的放射線療法にテモゾロミドによる術後補助化学療法を上乗せすることにより、1p/19q co-deletionのない退形成性神経膠腫患者の生存期間が延長することが示唆された。推定5年生存率は、放射線療法と術後補助化学療法の併用群で56%であったのに対し、テモゾロミドによる術後補助化学療法の非併用群では44%であった。増悪までの期間中央値は、テモゾロミド併用群で2倍以上であった（42.8か月対19か月）。これらの結果は、この希少脳腫瘍患者の治療選択肢を拡大し治療法を変化させるはずである、と筆者らは述べている。

Patients with anaplastic glioma without 1p/19q co-deletion benefit from adjuvant chemotherapy, according to early results from a European phase III trial. The estimated five-year survival rates were 56% with radiation therapy and adjuvant temozolomide versus 44% without adjuvant temozolomide. Addition of adjuvant temozolomide also delayed disease progression by more than two years.

The study was presented at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting.

"Until this study, doctors had no evidence to support the use of adjuvant temozolomide in patients with grade III anaplastic glioma," said lead study author Martin J. van den Bent, MD, a professor of neuro-oncology at Erasmus MC Cancer Center in Rotterdam, The Netherlands. "These findings should expand treatment choices and change the way we treat patients with this rare form of brain cancer."

Co-deletion of chromosome arms 1p and 19q occurs in a specific type of brain cancer. Patients who have this genetic abnormality tend to respond better to chemotherapy and live longer. The Concurrent and Adjuvant Temozolomide Chemotherapy in Non---1p/19q Deleted Anaplastic Glioma (CATNON) trial was limited to patients who lack 1p/19q co-deletion (a separate trial focuses on patients who have this marker).

Researchers randomly assigned 748 patients to four different treatment groups:

Radiation therapy alone
Temozolomide during radiation therapy
Temozolomide during and after radiation therapy
Temozolomide after radiation therapy (adjuvant temozolomide)

The study was conducted by the European Organisation for Research and Treatment of Cancer (EORTC) and enrolled patients in 118 institutions in Europe, North America, and Australia.

Patients who received temozolomide after radiation therapy with or without concurrent temozolomide had slower disease progression than those treated without adjuvant therapy. The median time to disease progression was more than double in the adjuvant temozolomide group (42.8 months vs. 19 months).

The median overall survival has not been reached in patients treated with adjuvant temozolomide. Long-term survival estimates also support the use of adjuvant temozolamide; 56% of patients were alive at five years with adjuvant temozolomide compared to 44% with radiation therapy alone or with temozolomide given during radiation therapy. The results of the temozolomide treatment given only during radiation therapy are not yet available and final data from this study are expected in 2020.

Temozolomide is an oral drug and is generally well tolerated by patients. The most common toxicities in the temozolomide study arms were mainly hematologic (e.g., low platelets and white blood cells), with severe toxicity in 5-10% of patients.

Future research will focus on identifying patients who are most likely to benefit from adjuvant temozolomide. The researchers plan to assess or re-examine additional genetic abnormalities known to affect prognosis in this cancer: MGMT promotor methylation and IDH mutation.

"As physicians, our goal is to make every treatment matter, which includes recommending only treatments that our patients need – no more and no less. This study offers a good answer to a long-standing question, showing that adding temozolomide following radiation or concurrent chemoradiation offers clear benefits. For decades, anaplastic glioma has proven not only hard to treat, but also hard to study because it is so rare, making this finding even more important," said Brian Alexander, MD, MPH, ASCO Expert in brain cancers.

Anaplastic gliomas are uncommon, accounting for about 2% of primary brain cancers and highly aggressive tumors. They often occur in young adults – the median age at diagnosis is 35 to 50 years. Grade III anaplastic gliomas can grow quickly and progress to glioblastoma within a few years of diagnosis.

This study received funding from an unrestricted grant from Schering Plough/MSD, by the EORTC Cancer Research Fund, by Cancer Research UK, by NRG grants U10CA180868 (NRG Oncology Operations) and U10CA180822 (NRG Oncology SDMC); and by Cancer Australia. Temozolomide was made available for this study by Schering Plough/MSD.