Prostate cancer: news on treatment and control options

Prostate cancer: news on treatment and control options

3 Mar 2015

A set of new findings on prostate cancer were presented during a recent international conference, including

• Low-dose brachyterapy boosts
• An update to the cabozantinib drug
• Androgen deprivation therapy.

Low-dose brachytherapy boost helps control prostate cancer

A trial tested the impact of "boosts" of low-dose brachytherapy. The outcome shows that these boosts held prostate cancer in check significantly better than dose-escalated external-beam radiation therapy (EBRT) in men with unfavorable-risk disease,.

Clinical design and findings on brachytherapy

The findings came from a randomized trial involving 398 patients with high-risk localized prostate cancer. All patients received 12 months of androgen deprivation therapy (ADT) and EBRT and were randomized to the low-dose iodine-125 brachytherapy boost to the prostate or an EBRT boost.

The primary endpoint was relapse-free survival. The two treatment arms had identical 94% relapse-free survival at 3 years. Thereafter, the brachytherapy arm demonstrated significantly better relapse-free survival:

• 89% versus 77% at 5 years,
• 86% versus 71% at 7 years, and
• 83% versus 63% at 9 years.

Brachytherapy boosts: detailed results

Patients treated with brachytherapy after androgen deprivation therapy and whole-pelvis EBRT had an estimated 9-year relapse-free survival of 83% compared with 63% for patients who received a conformal EBRT boost. The difference in favor of brachytherapy emerged after 5 years of follow-up, according to Scott Tyldesley, MD, of the British Columbia Cancer Agency in Vancouver.

"In the context of 12 months of androgen deprivation therapy and whole pelvis external beam radiotherapy, treatment with a low-dose pelvic brachytherapy boost results in a 50% reduction in biochemical relapse compared to dose-escalated EBRT to 78 Gray," Tyldesley said. "At 6.5 years of follow-up, there was no difference in overall survival, prostate cancer specific survival, or metastasis-free survival."

However, "there was increased late grade 3 or higher genitourinary toxicity with the low-dose rate boost, a 5% to 6% increase in the prevalence of late genitourinary toxicity," he said.

Assessment of late (6 years) toxicity showed that:

• 95% of patients in both arms were free of late gastrointestinal toxicity,
• 90% of patients in the EBRT arm were free of late genitourinary  toxicity, and
• 80% of patients in the brachytherapy arm were free of late genitourinary toxicity.

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Clinical updates on cabozantinib

Patients with metastatic castration-resistant prostate cancer (mCRPC) got no survival benefit from the small-molecule inhibitor cabozantinib (Cometriq) used as third- or fourth-line therapy according to a randomized trial.

Matthew R. Smith MD, PhD, of Massachusetts General Hospital Cancer Center in Boston reported final results from the phase 2, randomized COMET-1 trial involving 1,028 patients with mCRPC and progression during or after treatment with docetaxel and abiraterone (Zytiga) and/or enzalutamide (Xtandi). The patients were randomized 2:1 to cabozantinib or prednisone and followed until disease progression. The primary endpoint was overall survival.

Results of the study

Data analysis showed:

• Patients treated with cabozantinib had a median overall survival of 11.0 months versus 9.8 months with prednisone.
• Median progression-free survival in the cabozantinib arm was twice that of the prednisone control group.
• The primary analysis showed no significant difference between treatment groups. Progression-free survival in the cabozantinib arm was double that of the prednisone group.
• The cabozantinib group had a significantly higher rate of bone scan response and the duration of bone response was 5.8 months versus 1.8 months in favor of cabozantinib.

"Subgroup analyses suggested a larger improvement in overall survival in men with visceral metastases or who had received prior cabazitaxel," said Matthew R. Smith. "Cabozantinib was associated with significant improvements in bone-scan response, progression-free survival, time to first skeletal-related event, circulating tumor cell conversion, and bone biomarkers."

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Better disease control with androgen deprivation therapy

As showed in a phase 3 trial, a 6-month course of androgen deprivation therapy (ADT) added to radiation therapy led to significantly better biochemical relapse-free and disease-free survival than did irradiation alone for intermediate-risk prostate cancer.

More specifically:

• Patients who received ADT plus external beam radiotherapy (EBRT) total dose of 78 Gy had a 5-year biochemical failure rate of 2.4% compared with 13.2% for patients who received EBRT alone.
• ADT plus a 70-Gy dose of EBRT had a 5-year failure rate of 7.8%.
• Failure rates at 10 years were 34.5% with EBRT alone, 16.6% with ADT and 78 Gy EBRT, and 23.4% for ADT plus 70 Gy EBRT.

Similar advantages emerged for androgen deprivation therapy plus external beam radiotherapy with respect to disease-free survival rate. The 5-year disease-free survival  was:

• 97.6% for ADT-78 Gy EBRT,
• 93.1% for ADT-70 Gy EBRT, and
• 86.3% for 78 Gy EBRT alone.

Whereas, the 10-year disease-free survival was 89.8%, 77.2%, and 64.7%, for the two ADT arms and EBRT alone, respectively.

"In intermediate-risk prostate cancer, the use of short-term androgen deprivation therapy in association with prostate radiotherapy, even at lower doses, leads to a superior biochemical control and disease-free survival as compared to dose-escalated prostate radiotherapy alone," said Abdenour Nabid, MD, of Sherbrooke University Hospital Center in Canada.

Source: MedPage Today