First Trial to Show Adjuvant Therapy Benefit in Prostate Cancer Revealed

Howard M. Sandler, MD, MS

Howard M. Sandler, MD, MS

In the first phase III trial to show a benefit for adjuvant therapy in prostate cancer, treatment with an adjuvant combination of docetaxel, androgen deprivation therapy (ADT), and radiation therapy (RT) improved 4-year overall survival (OS) rates in patients with high-risk localized prostate cancer, when compared with ADT plus RT alone.

“For the first time, improvement in overall survival was observed in men with localized, high-risk, hormone-sensitive prostate cancer who received tolerable adjuvant chemotherapy,” said Howard M. Sandler, MD, MS, chair of radiation oncology at Cedars-Sinai Medical Center, during press briefing of the 2015 ASCO Annual Meeting.¹“The potential role [of this regimen] is consistent with and supported by our data and other studies such as STAMPEDE and CHAARTED.”

STAMPEDE, which is the largest randomized prostate cancer trial ever conducted, was also presented at the 2015 ASCO meeting. In this study, researchers reported that adding docetaxel to standard hormonal therapy significantly improved survival among men with newly diagnosed hormone-naïve advanced prostate cancer. In the phase III CHAARTED trial, which was presented at the 2014 ASCO Meeting, it was shown that docetaxel in combination with standard hormone therapy extended OS by nearly 14 months.

In the Sandler et al adjuvant study, the 4-year OS rates were 89% for men who received ADT and RT versus 93% for men treated with ADT, RT, and docetaxel (HR = 0.70; 90% CI, 0.51-0.98;P= .04).

A total of 612 men were enrolled in Radiation Therapy Oncology Group (RTOG) 0521 from December 2005 through August 2009. The trial was designed to detect improvement in 4-year OS rates from 86% to 93% with a 51% hazard reduction (HR = 0.49). The primary endpoint was OS.

Patients were eligible for the trial if they had a Gleason score 7-8, any T-stage, and prostate-specific antigen (PSA) >20; or Gleason score 8, T2, and any PSA; or Gleason score 9-10, any T-stage, any PSA.

“These patients were the highest of the high risk,” said Sandler. Locally advanced or high-risk localized prostate cancer has a relatively poor prognosis. Standard treatment involves radiotherapy and long-term hormonal treatment, he added.

All patients received ADT for 24 months and RT for 8 weeks at 75.6 Gy. Patients in the chemotherapy arm received 6-cycles of docetaxel plus prednisone in 21-day increments, starting 28 days after receiving RT.

After undergoing eligibility review and exclusion, 562 men were determined to be evaluable. These patients had a median age of 66 years, median PSA of 15.1, 53% had Gleason score 9 to 10, and 27% had prostate cancer staged at cT3-4. All patients had PSA levels ≤150 and average follow-up was 5.5 years.

At a median 5.5-year follow-up, 5-year disease-free survival rates were 66% in the standard therapy group versus 73% in the docetaxel group (HR = 0.76; 95% CI: 0.57-1.00;P= .05). There was also a reduction in the incidence of distant metastasis and other secondary endpoints with the addition of docetaxel, a significant clinical finding, Sandler noted.

There were 52 centrally reviewed deaths in the ADT/RT arm versus 36 in the chemotherapy group. There were fewer deaths due to prostate cancer or treatment (16 vs 20) or due to other causes or unknown (20 vs 32) with chemotherapy versus without, respectively.

“Whether or not adding chemotherapy becomes a standard of care for this population remains to be seen,” said Sandler. “For the right patient and for the right physician, there might be justification for considering it. This analysis that looked at a four-year endpoint is relatively early and additional follow up will likely be further enlightening.”

The toxicity with the addition of docetaxel was labeled "acceptable" by the study authors. There was one death that was unlikely related to treatment in the ADT plus RT arm and two deaths that were possibly related to treatment in the chemotherapy arm.

“Adjuvant chemotherapy has delivered major survival gains to people with several of the most common types of cancer, and now we’re finally seeing the same with prostate cancer,” ASCO expert Charles J. Ryan, MD, from the University of California, San Francisco, said concerning the results. “Here we have a powerful new use for a long-established therapy. It’s an advance that would not have been possible without federally funded clinical trials.”

Sandler HM, Hu C, Rosenthal SA, et al. A phase III protocol of androgen suppression (AS) and 3DCRT/IMRT vs AS and 3DCRT/IMRT followed by chemotherapy (CT) with docetaxel and prednisone for localized, high-risk prostate cancer (RTOG 0521).J Clin Oncol. 2015;33 (suppl; abstr LBA5002).