Adjuvant Procarbazine, Lomustine And Vincristine Boost Low-Grade Glioma Survival

Combining chemotherapy and radiotherapy significantly improves survival outcomes for young adults with grade 2 glioma

medwireNews: Long-term results demonstrate a significant gain in overall survival (OS) with the addition of procarbazine, lomustine and vincristine to radiotherapy for young patients with low-grade glioma.

After a median 11.9 years of follow-up, 55% of the patients with grade 2 astrocytoma, oligoastroyctoma or oligodendroglioma had died, report Jan Buckner, from the Mayo Clinic in Rochester, Minnesota, USA, and co-workers.

The median OS was 13.3 years for the 125 patients who were randomly assigned to receive six cycles of the chemotherapy regimen plus 54 Gy of radiation versus just 7.8 years for the 126 patients given radiotherapy alone.

Ten-year OS was achieved by 60% of patients given combined treatment versus 40% of those treated with only radiation; the corresponding 10-year rates of progression-free survival (PFS) were 51% and 21%.

The results published in The New England Journal of Medicine follow an earlier report of improved PFS but not OS for the chemotherapy-treated patients in 2012 after 5.9 years follow-up.

Participants in the current phase III trial were either aged less than 40 years and had undergone subtotal resection or biopsy, or were at least 40 years old and had undergone any resection or biopsy of the tumour, the authors explain.

Multivariate analysis confirmed that OS after 1 year was significantly more likely if patients received chemotherapy (hazard ratio [HR]=0.35), had oligodendroglioma histology versus oligoastocytoma or astrocytoma (HR=0.35 and 0.38, respectively), and were younger than 40 years versus older (HR=0.50).

In addition, the presence of the IDH1 R132H mutation, regardless of treatment, was significantly associated with improved PFS after 1 year, as well as better OS after 1 year, although this did not reach significance.

“The differences in survival cannot be explained on the basis of treatment after tumor progression because patients who received radiation therapy alone had a shorter time to progression and more therapeutic interventions after progression than did those who received radiation therapy plus chemotherapy”, the researchers observe.

However, acknowledging that it took several years for the PFS and OS curves of the two treatment groups to separate, the team comments: “If radiation therapy plus chemotherapy is effective in all patients, we would expect the curves to begin separation much sooner.”

They therefore believe there is a small, “elusive”, cohort of patients who do not respond to chemotherapy plus radiation.

Most toxicities were grade 1 or 2 and “consistent” with other multiagent chemotherapy regimens, Jan Buckner et al note that combined treatment was associated with more frequent and more severe side effects than radiation alone.

While acknowledging the “substantial” treatment benefit with the combined regimen, they conclude: “Patients and their physicians will have to weigh whether the longer survival justifies the more toxic therapeutic approach.”

Reference

Buckner JC, Shaw EG, Pugh SL, et al. Radiation plus procarbazine, CCNU, and vincristine in low-grade glioma. N Engl J Med 2016; 374: 1344–1355. DOI: 10.1056/NEJMoa1500925

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