MHSPC: Increased Survival with Added Docetaxel Confirmed Long-Term (CME/CE) | IUK Med Online
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MHSPC: Increased Survival with Added Docetaxel Confirmed Long-Term (CME/CE)

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MHSPC: Increased Survival with Added Docetaxel Confirmed Long-Term

13-month advantage in median overall survival

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  • by Contributing Writer, MedPage Today

Action Points

  • Docetaxel plus androgen-deprivation therapy (ADT) significantly improved long-term overall survival (OS) in men with metastatic hormone-sensitive prostate cancer (mHSPCA), compared with those who received ADT alone.
  • Note that longer follow-up in this randomized clinical trial confirmed the interim analysis that found the effect of docetaxel was more pronounced for patients with high-volume disease.

For men with metastatic hormone-sensitive prostate cancer (mHSPC), significant long-term improvement in overall survival (OS) has been confirmed for those who received docetaxel plus androgen-deprivation therapy (ADT), compared with those who received ADT alone.

As an interim analysis of the Chemohormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer (CHAARTED) had demonstrated, the survival benefit in favor of the chemohormonal arm was reported for the study population as a whole, but the greatest benefit occurred among men with high-volume disease. At a median follow-up of 28.9 months, there was a 13-month difference in median OS among men randomized to have docetaxel plus ADT, at 57.6 months compared with 44.0 months for men treated with ADT alone.

At the time of the interim analysis, 101 patients had died in the chemotherapy-plus-ADT arm compared with 136 patients in the ADT-alone arm.

Now, as shown in the new study in the Journal of Clinical Oncology by Christos Kyriakopoulos, MD, of the University of Wisconsin School of Medicine and Public Health in Madison, and colleagues, with 188 deaths in the combination arm and 211 in the ADT-alone arm, median OS was 10.4 months longer in the chemohormonal arm at the same 57.6 months after a median follow-up of 53.7 months, compared with 47.2 months in the hormonal-alone arm alone (hazard ratio [HR], 0.72; 95% CI, 0.59 to 0.89; P=.0018).

“This is a practice-changing, confirmatory follow-up study that tells us that front-line treatment with docetaxel plus ADT will be one of the new standards for high-risk metastatic prostate cancer, although this does not seem to apply to low-risk disease,” Derek Raghavan, MD, PhD, president of Carolinas Health Care System’s Levine Cancer Center in Charlotte, N.C., a genitourinary cancer specialist not affiliated with the study, affirmed via email to MedPage Today.

Until the CHAARTED results were released, it was not clear whether giving chemotherapy upfront along with ADT could delay the inevitable transformation of mHSPC into castrate-resistant prostate cancer (CRPC) and improve both quality of life and OS. Kyriakopoulos et al randomized 790 participants with mHSPC to either ADT in combination with docetaxel at a dose of 75 mg/m2 for up to six cycles of ADT alone. The primary endpoint of the study was overall survival.

The results were additionally analyzed by prospectively defined low- and high-volume disease subgroups. In the study, high-volume disease was defined as the presence of visceral metastases either with or without four or more bone metastases, one of which had to be outside the vertebral column and pelvis. A total of 513 participants were classified as having high-volume disease, with roughly equal numbers of patients receiving the combination of docetaxel plus ADT and ADT alone.

“Longer follow-up confirmed that the effect of docetaxel was more pronounced for patients with high-volume disease,” the team reported.

At the same median follow-up of 53.7 months, median OS in the high-volume disease subgroup was 16.8 months longer in the combination arm. at a median of 51.2 months compared with 34.3 months for the ADT-alone arm — HR 0.63 (95% CI, 0.50 to 0.79; P<.001). In comparison, median OS among men with low-volume disease treated with the same combination was 63.5 months, at a median follow-up of 53.8 months compared with a median survival that had not yet been reached for the ADT-alone arm at an HR of 1.04 (95% CI, 0.70 to 1.55; P=.86), the researchers added.

Time to the development of CRPC and time to clinical progression were also assessed. For the overall cohort, the time to CRPC was 39% longer, at 19.4 months in the docetaxel-plus-ADT arm, versus 11.7 months in the ADT-alone arm (HR, 0.61; 95% CI, 0.52 to 0.73; P<.001). Median time to clinical progression, again for the overall cohort, was also 38% longer, at 33.0 months in the combination arm versus 19.8 months in the ADT-alone arm, at an HR of 0.62 (95% CI, 0.51 to 0.75; P<.001).

Other major findings:

  • For patients with high-volume disease, the median time to CRPC was 42% longer, at 14.9 months for the chemohormonal arm compared with 8.6 months for the ADT-alone arm, at an HR of 0.59 (95% CI, 0.47 to 0.71; P<.001)
  • For men with low-volume disease, the median time to CRPC was 30% longer, at 31.0 months among men in the combination arm compared with 22.7 months for those treated with ADT alone, at an HR of 0.70 (95% CI, 0.50 to 0.96; P=.03)
  • For men with high-volume disease, the median time to clinical progression at 27.3 months was 47% longer for those treated with the combination compared with a median of 13.0 months, at an HR of 0.53 (95% CI, 0.42 to 0.67; P<.001) for those in the ADT-alone arm
  • For men with low-volume disease, the median time to clinical progression was virtually identical in both treatment groups, at 42.5 months in the combination arm versus 44.3 months in the ADT-alone arm, at an HR of 0.86 (95% CI, 0.60 to 1.25; P=.43)

“With longer follow-up, the clinical benefit observed with chemohormonal therapy was confirmed for patients with high-volume disease regardless of whether they had relapsed after [prior local therapy] of the prostate with or without curative intent,” the researchers concluded. “In contrast, the subgroup with low-volume disease showed no evidence of survival benefit when docetaxel was added (HR, 1.04 with 100 deaths), despite the [earlier] analysis showing a nonsignificant HR of 0.60 with 44 deaths.”

The team cautioned that the results need to be viewed in light of recent guidelines issued by the American Society of Clinical Oncology indicating that both docetaxel and abiraterone (Zytiga) represent two separate standards of care for mHSPC, since the addition of either drug to ADT significantly improved OS in men with newly diagnosed metastatic noncastration-resistant prostate cancer. Raghavan also emphasized that it is not yet clear whether abiraterone or enzalutamide (XTANDI) plus ADT have equivalent efficacy in this context, although the combination approach seems to be superior to ADT alone, as he indicated.

“Added considerations in this comparison will include toxicity, ease of delivery, patient compliance, and cost,” he said. In addition, “fiscal toxicity has become a much bigger factor [in cancer therapy, even though] it is pleasing to see meaningful increases in median- and long-term survival from these new treatment algorithms.”

Kyriakopoulos reported a financial relationship with Exelixis, and other co-authors reported financial relationships with multiple pharmaceutical companies.

Sanofi supplied the docetaxel used in the study.

Raghavan reported having no relevant financial conflicts of interest.

2018-04-16T15:00:00-0400
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Medpage Today

MHSPC: Increased Survival with Added Docetaxel Confirmed Long-Term

13-month advantage in median overall survival

MedpageToday

  • register today

    Earn Free CME Credits by reading the latest medical news in your specialty.

    sign up

  • by Contributing Writer, MedPage Today

Action Points

  • Docetaxel plus androgen-deprivation therapy (ADT) significantly improved long-term overall survival (OS) in men with metastatic hormone-sensitive prostate cancer (mHSPCA), compared with those who received ADT alone.
  • Note that longer follow-up in this randomized clinical trial confirmed the interim analysis that found the effect of docetaxel was more pronounced for patients with high-volume disease.

For men with metastatic hormone-sensitive prostate cancer (mHSPC), significant long-term improvement in overall survival (OS) has been confirmed for those who received docetaxel plus androgen-deprivation therapy (ADT), compared with those who received ADT alone.

As an interim analysis of the Chemohormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer (CHAARTED) had demonstrated, the survival benefit in favor of the chemohormonal arm was reported for the study population as a whole, but the greatest benefit occurred among men with high-volume disease. At a median follow-up of 28.9 months, there was a 13-month difference in median OS among men randomized to have docetaxel plus ADT, at 57.6 months compared with 44.0 months for men treated with ADT alone.

At the time of the interim analysis, 101 patients had died in the chemotherapy-plus-ADT arm compared with 136 patients in the ADT-alone arm.

Now, as shown in the new study in the Journal of Clinical Oncology by Christos Kyriakopoulos, MD, of the University of Wisconsin School of Medicine and Public Health in Madison, and colleagues, with 188 deaths in the combination arm and 211 in the ADT-alone arm, median OS was 10.4 months longer in the chemohormonal arm at the same 57.6 months after a median follow-up of 53.7 months, compared with 47.2 months in the hormonal-alone arm alone (hazard ratio [HR], 0.72; 95% CI, 0.59 to 0.89; P=.0018).

"This is a practice-changing, confirmatory follow-up study that tells us that front-line treatment with docetaxel plus ADT will be one of the new standards for high-risk metastatic prostate cancer, although this does not seem to apply to low-risk disease," Derek Raghavan, MD, PhD, president of Carolinas Health Care System's Levine Cancer Center in Charlotte, N.C., a genitourinary cancer specialist not affiliated with the study, affirmed via email to MedPage Today.

Until the CHAARTED results were released, it was not clear whether giving chemotherapy upfront along with ADT could delay the inevitable transformation of mHSPC into castrate-resistant prostate cancer (CRPC) and improve both quality of life and OS. Kyriakopoulos et al randomized 790 participants with mHSPC to either ADT in combination with docetaxel at a dose of 75 mg/m2 for up to six cycles of ADT alone. The primary endpoint of the study was overall survival.

The results were additionally analyzed by prospectively defined low- and high-volume disease subgroups. In the study, high-volume disease was defined as the presence of visceral metastases either with or without four or more bone metastases, one of which had to be outside the vertebral column and pelvis. A total of 513 participants were classified as having high-volume disease, with roughly equal numbers of patients receiving the combination of docetaxel plus ADT and ADT alone.

"Longer follow-up confirmed that the effect of docetaxel was more pronounced for patients with high-volume disease," the team reported.

At the same median follow-up of 53.7 months, median OS in the high-volume disease subgroup was 16.8 months longer in the combination arm. at a median of 51.2 months compared with 34.3 months for the ADT-alone arm -- HR 0.63 (95% CI, 0.50 to 0.79; P<.001). In comparison, median OS among men with low-volume disease treated with the same combination was 63.5 months, at a median follow-up of 53.8 months compared with a median survival that had not yet been reached for the ADT-alone arm at an HR of 1.04 (95% CI, 0.70 to 1.55; P=.86), the researchers added.

Time to the development of CRPC and time to clinical progression were also assessed. For the overall cohort, the time to CRPC was 39% longer, at 19.4 months in the docetaxel-plus-ADT arm, versus 11.7 months in the ADT-alone arm (HR, 0.61; 95% CI, 0.52 to 0.73; P<.001). Median time to clinical progression, again for the overall cohort, was also 38% longer, at 33.0 months in the combination arm versus 19.8 months in the ADT-alone arm, at an HR of 0.62 (95% CI, 0.51 to 0.75; P<.001).

Other major findings:

  • For patients with high-volume disease, the median time to CRPC was 42% longer, at 14.9 months for the chemohormonal arm compared with 8.6 months for the ADT-alone arm, at an HR of 0.59 (95% CI, 0.47 to 0.71; P<.001)
  • For men with low-volume disease, the median time to CRPC was 30% longer, at 31.0 months among men in the combination arm compared with 22.7 months for those treated with ADT alone, at an HR of 0.70 (95% CI, 0.50 to 0.96; P=.03)
  • For men with high-volume disease, the median time to clinical progression at 27.3 months was 47% longer for those treated with the combination compared with a median of 13.0 months, at an HR of 0.53 (95% CI, 0.42 to 0.67; P<.001) for those in the ADT-alone arm
  • For men with low-volume disease, the median time to clinical progression was virtually identical in both treatment groups, at 42.5 months in the combination arm versus 44.3 months in the ADT-alone arm, at an HR of 0.86 (95% CI, 0.60 to 1.25; P=.43)

"With longer follow-up, the clinical benefit observed with chemohormonal therapy was confirmed for patients with high-volume disease regardless of whether they had relapsed after [prior local therapy] of the prostate with or without curative intent," the researchers concluded. "In contrast, the subgroup with low-volume disease showed no evidence of survival benefit when docetaxel was added (HR, 1.04 with 100 deaths), despite the [earlier] analysis showing a nonsignificant HR of 0.60 with 44 deaths."

The team cautioned that the results need to be viewed in light of recent guidelines issued by the American Society of Clinical Oncology indicating that both docetaxel and abiraterone (Zytiga) represent two separate standards of care for mHSPC, since the addition of either drug to ADT significantly improved OS in men with newly diagnosed metastatic noncastration-resistant prostate cancer. Raghavan also emphasized that it is not yet clear whether abiraterone or enzalutamide (XTANDI) plus ADT have equivalent efficacy in this context, although the combination approach seems to be superior to ADT alone, as he indicated.

"Added considerations in this comparison will include toxicity, ease of delivery, patient compliance, and cost," he said. In addition, "fiscal toxicity has become a much bigger factor [in cancer therapy, even though] it is pleasing to see meaningful increases in median- and long-term survival from these new treatment algorithms."

Kyriakopoulos reported a financial relationship with Exelixis, and other co-authors reported financial relationships with multiple pharmaceutical companies.

Sanofi supplied the docetaxel used in the study.

Raghavan reported having no relevant financial conflicts of interest.

2018-04-16T15:00:00-0400
Take Posttest Comments

Accessibility Statement

At MedPage Today, we are committed to ensuring that individuals with disabilities can access all of the content offered by MedPage Today through our website and other properties. If you are having trouble accessing www.medpagetoday.com, MedPageToday's mobile apps, please email legal@ziffdavis.com for assistance. Please put "ADA Inquiry" in the subject line of your email.



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