Olaparib in combination with temozolomide for glioma

Lauren R.
Schaff et al.
of Memorial Sloan-Kettering Cancer Center in New York, USA, retrospectively analyzed the efficacy and adverse effects
of olaparib + TMZ combination in the treatment of glioma patients.

The results were published online in Neurology in August 2022
.

- Excerpted from the article chapter

【Ref: Schaff LR, et al.
Neurology.
2022 Aug 10:10.
1212/WNL.
0000000000201203.
doi:10.
1212/WNL.
0000000000201203.
[Epub ahead of print] 】

Research background

Glioma is a common intracranial malignancy that can be avoided
after treatment.

There is currently no consensus on
treatment options for recurrent gliomas.

Recent studies using polyadenosine diphosphate ribose polymerase (PARP) inhibitors for the treatment of gliomas with isocitrate dehydrogenase (IDH) mutations have demonstrated efficacy
.

Kills tumor cells
by producing homologous recombinant defects (HRD).

Even in the absence of HRD, PARP inhibitors exert a synergistic therapeutic effect
with the DNA alkylating agent temozolomide (TMZ).

Currently, the results of olaparib in combination with TMZ are limited to the glioblastoma population, and the number of studies is limited
.

Lauren R.
Schaff et al.
of Memorial Sloan-Kettering Cancer Center in New York, USA, retrospectively analyzed the efficacy and adverse effects
of olaparib + TMZ combination in the treatment of glioma patients.

The results were published online in Neurology in August 2022
.

Research methods

The study included 20 patients
treated with olaparib + TMZ between September 2018 and December 2021.

Collect medical records
of glioma characteristics, treatment history, side effects, and laboratory test results.

Radiographic responses
were assessed according to RANO criteria.

Progression-free survival (PFS)
from treatment initiation was calculated using the Kaplan Meier method.

Study results

The median age of the 20 patients was 42 years (24-75 years); The median Karnofsky score is 90 (60–100).


Glioma subtypes included 5 cases of IDH mutant oligodendroglioma, 4 cases of IDH mutant WHO grade II-III astrocytoma, 7 cases of IDH mutant WHO grade IV astrocytoma and 4 cases of IDH wild-type glioma, including 1 case of diffuse midline glioma and 3 cases of glioblastoma, of which 1 case was a BRCA1 mutant patient
.

All patients take olaparib at a dose of 150 mg 3 times / week; Twelve patients took TMZ 50mg/m²/day, and 8 patients took 75mg/m²/day
.

Ten patients continued treatment, while the other 10 patients received 6 weeks of treatment with a 2-3 week
break.

Side reactions were: 14 cases of lymphopenia, 10 cases of leukopenia, 7 cases of anemia, 6 cases of thrombocytopenia, 6 cases of elevated alanine aminotransferase, 4 cases of elevated aspartate aminotransferase, 4 cases of neutropenia and 1 case of hypomagnesemia
.

One patient developed grade 4 pneumocystis pneumonia (PCP) (subsequently recovered
).

Two patients discontinued treatment for PCP pneumonia and no treatment-related deaths
occurred.

Of the 20 patients, 16 showed a complete response, 3 had a partial response, and 3 were stable
.

The objective response rate of WHO grade II-III IDH mutant glioma patients was 50%, and the progression-free survival was 7.
8 months
.

Patients with WHO grade IV IDH mutant astrocytoma and IDH wild-type glioma had no objective remission, and only 2 patients had stable disease, and their PFS were 1.
3 months and 2.
0 months
, respectively.

Conclusion of the study

In summary, this study analyzes the efficacy and complications of olaparib + TMZ combination in glioma patients, laying a foundation
for further clinical trials.