Elsevier

Urology

Volume 81, Issue 6, June 2013, Pages 1297-1302
Urology

Medical Oncology
Lower Baseline Prostate-specific Antigen Is Associated With a Greater Overall Survival Benefit From Sipuleucel-T in the Immunotherapy for Prostate Adenocarcinoma Treatment (IMPACT) Trial

https://doi.org/10.1016/j.urology.2013.01.061Get rights and content

Objective

To explore the prognostic and predictive value of baseline variables in 512 patients with metastatic castration-resistant prostate cancer from the phase III Immunotherapy for Prostate Adenocarcinoma Treatment (IMPACT) trial who were randomized to receive sipuleucel-T or control.

Methods

The most powerful of these prognostic factors, baseline prostate-specific antigen (PSA), was subdivided into quartiles to evaluate treatment effect patterns. Cox regression analyses were used to assess predictors of overall survival (OS) and sipuleucel-T treatment effect within PSA quartiles. Median OS was estimated by the Kaplan-Meier method.

Results

PSA was the strongest baseline prognostic factor (P <.0001). Furthermore, the sipuleucel-T treatment effect appeared greater with decreasing baseline PSA. The OS hazard ratio for patients in the lowest baseline PSA quartile (≤22.1 ng/mL) was 0.51 (95% confidence interval, 0.31-0.85) compared with 0.84 (95% confidence interval, 0.55-1.29) for patients in the highest PSA quartile (>134 ng/mL). Estimated improvement in median survival varied from 13.0 months in the lowest baseline PSA quartile to 2.8 months in the highest quartile. Estimated 3-year survival in the lowest PSA quartile was 62.6% for sipuleucel-T patients and 41.6% for control patients, representing a 50% relative increase.

Conclusion

The greatest magnitude of benefit with sipuleucel-T treatment in this exploratory analysis was observed among patients with better baseline prognostic factors, particularly those with lower baseline PSA values. These findings suggest that patients with less advanced disease may benefit the most from sipuleucel-T treatment and provide a rationale for immunotherapy as an early treatment strategy in sequencing algorithms for metastatic castration-resistant prostate cancer.

Section snippets

Study Design

The study design and patient inclusion have been previously described in detail.3 The trial enrolled patients with mCRPC. Initially, only men with asymptomatic disease, a Gleason score of ≤7, and PSA of ≥5 ng/mL were enrolled. The trial was subsequently amended to include men with any Gleason score and minimally symptomatic disease. Patients with ECOG PS of ≥2, visceral metastases, or previous treatment with >2 chemotherapy regimens were excluded.3 Further details of the trial are registered at

Patients

Patients in the study population had a median age of 71 years, and approximately 82% of enrolled patients were chemotherapy-naive.3 Baseline clinical characteristics for the prognostic factors previously identified as important in this patient population were similar in the 2 study groups.3

Prognostic Factors and Efficacy by Prognostic Subgroup

All of the variables identified by Halabi et al6 and available for evaluation in IMPACT (PSA, LDH, Hgb, ECOG PS, ALP, and Gleason score) were significant independent prognostic factors for survival (P <.05)

Comment

We have previously demonstrated that sipuleucel-T prolongs survival in men with mCRPC and is effective in multiple patient subgroups. In this exploratory analysis, we show a trend toward a more pronounced treatment effect in patients with better baseline prognostic features. This appeared most prominent with baseline PSA, where those in the lowest quartile (<22.1 ng/mL) achieved a 49% reduction in the risk of death (HR, 0.51; 95% CI, 0.31-0.85) and a median survival difference of 13.0 months

Conclusions

The results from our exploratory analyses suggest that the greatest magnitude of benefit with sipuleucel-T treatment was observed among patients with better baseline prognostic factors and particularly those with lower baseline PSA values. These findings provide a rationale for immunotherapy as an early step in sequencing treatment algorithms for mCRPC and also suggest a greater benefit when immunotherapy is used earlier in the treatment paradigm.

Acknowledgments

Medical writing assistance was provided by Emma Warr and Stuart Langley of Gardiner-Caldwell Communications and funded by Dendreon Corporation.

References (24)

  • A.J. Armstrong et al.

    A contemporary prognostic nomogram for men with hormone-refractory metastatic prostate cancer: ATAX327 Study Analysis

    Clin Cancer Res

    (2007)
  • B. Seruga et al.

    Cytokines and their relationship to the symptoms and outcome of cancer

    Nat Rev Cancer

    (2008)
  • Cited by (0)

    Financial Disclosure: James B. Whitmore, Robert Sims, and Mark W. Frohlich are employees of Dendreon Corporation. Paul F. Schellhammer is on the advisory board and speakers bureau for Dendreon Corporation and on the advisory board for Janssen. Gerald Chodak is a consultant for Dendreon Corporation and Watson and is a speaker for Dendreon Corporation, Amgen, and Watson. Philip W. Kantoff is on the advisory boards for Dendreon Corporation, Bavarian Nordic Immunotherapeutics, Bellicum, Sanofi, Janssen, Bristol Myers Squibb, BIND, and Pfizer.

    Funding Support: This study was funded by Dendreon Corporation.

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