Stupp Trial: What the Glioblastoma Trial Found

In brief

Before 2005, the standard treatment for newly diagnosed glioblastoma was surgery followed by radiotherapy. The trial led by Roger Stupp asked whether adding the chemotherapy drug temozolomide to that radiotherapy would help people live longer. It did. The gain was modest in months and large in proportion: median survival rose from 12.1 to 14.6 months, and the share of people alive at five years rose from 1.9% to 9.8%.

Trial at a glance

Field	Detail
Trial	EORTC 26981-22981 / NCIC CE.3 (the Stupp trial)
Identifier	NCT00006353
Phase	Phase 3
Design	Randomized, open-label, 85 centers
Cancer type	Newly diagnosed glioblastoma
Comparator	Radiotherapy alone (60 Gy over six weeks)
Primary endpoint	Overall survival
Enrollment	573 patients randomized

Who took part

573 adults with newly diagnosed, biopsy-confirmed glioblastoma were randomized between August 2000 and March 2002. The registry set the age limit at 18 to 70 years. Median age was 56, and 84% had already had debulking surgery to remove as much tumor as safely possible.

What the trial found

One group received radiotherapy alone: 2 Gy a day, five days a week, for six weeks, totalling 60 Gy. The other received the same radiotherapy plus temozolomide every day throughout radiotherapy, then up to six further cycles taken for five days out of every 28, at a higher daily amount worked out from body size.

At a median follow-up of 28 months, median survival was 14.6 months with radiotherapy plus temozolomide and 12.1 months with radiotherapy alone. The hazard ratio for death was 0.63 (95% CI, 0.52 to 0.75; P<0.001). Two-year survival was 26.5% versus 10.4%. Grade 3 or 4 blood-count toxicity during the combined phase affected 7% of patients.

The five-year analysis, published in 2009, showed the gap held. Survival with temozolomide was 27.2% at two years, 16.0% at three, 12.1% at four and 9.8% at five years, against 10.9%, 4.4%, 3.0% and 1.9% with radiotherapy alone. Benefit appeared across every clinical subgroup studied, including patients aged 60 to 70. Methylation of the MGMT gene promoter, assessed later in tumor tissue from 206 patients, was the strongest predictor of who benefited.

What changed in practice

This regimen became the standard. The National Cancer Institute lists temozolomide as approved for glioblastoma "with radiation therapy in patients with newly-diagnosed cancer and then alone as maintenance therapy." Almost every glioblastoma trial since has used the Stupp regimen as its control arm.

What this story cannot tell you

• It does not tell you glioblastoma became curable. Most participants in both groups died within two years, and 89% of the temozolomide group had died by five years.
• It does not apply directly to people over 70, who were outside the entry criteria. A separate 2017 trial in patients aged 65 and older found that adding temozolomide to a shorter three-week radiotherapy course raised median survival from 7.6 to 9.3 months (hazard ratio 0.67; 95% CI, 0.56 to 0.80).
• It cannot tell you whether you personally will benefit. MGMT promoter methylation status predicted benefit, but it was tested retrospectively in only some tumors, and it is a probability, not a promise.
• Treatment has moved on in ways this trial could not anticipate. A 2017 randomized trial found that adding tumor-treating fields to maintenance temozolomide raised median overall survival from 16.0 to 20.9 months (hazard ratio 0.63; 95% CI, 0.53 to 0.76), at the cost of skin irritation under the scalp arrays in 52% of users.

Questions worth asking

• Has my tumor been tested for MGMT promoter methylation, and what did it show?
• Given my age and how much tumor was removed, is the standard six-week course right for me?
• What clinical trials are open for newly diagnosed glioblastoma at this centre?

Sources

This article was written from the sources below, which were checked on the source-check date shown above.

• NEJM 2005: Radiotherapy plus Concomitant and Adjuvant Temozolomide for Glioblastoma (primary)
• Lancet Oncology 2009: Five-year analysis of the EORTC-NCIC trial (primary)
• ClinicalTrials.gov: NCT00006353 (registry)
• NCI: Temozolomide (reference)
• NEJM 2017: Short-Course Radiation plus Temozolomide in Elderly Patients (supporting)
• JAMA 2017: Tumor-Treating Fields plus Maintenance Temozolomide (supporting)

Related reading: brain tumors and brain tumor treatment.

How this article was prepared

Prepared by Cancer Explained's AI-assisted editorial system and checked against the sources listed above. This article has not been reviewed by a healthcare professional unless a named reviewer is specifically shown.

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