VOLUME
33
䡠
NUMBER
12
䡠
APRIL
20
2015
JOURNAL OF CLINICAL ONCOLOGY
E
D
I
T
O
R
I
A
L
Making Progress on Progression in Metastatic Prostate Cancer Andrew J. Armstrong, Duke Cancer Institute, Duke University, Durham, NC Susan Halabi, Alliance Statistics and Data Center, Duke University, Durham, NC See accompanying articles on page 1348 and 1356
Determining clinical benefit to therapy is among the most critical aspects of oncology care. At the individual level, this determination influences cessation or continuation of therapy and can dramatically affect patient and family perceptions of hope and optimism. At the trial level, these determinations affect regulatory approvals, optimal care delivery, and the chance of a therapy reaching the clinic. In men with metastatic castration-resistant prostate cancer (CRPC), a number of challenges exist in assessing clinical benefit to therapies. First, the vast majority of men have metastatic disease confined predominantly to bone, making response challenging to assess using traditional RECIST criteria1 that were developed for other cancer types. Second, prostate-specific antigen (PSA) as a marker of response may be valuable in some contexts such as with androgen-receptor directed therapies,2 but in other settings, PSA may not drop to arbitrary degrees despite the use of chemotherapies or immunotherapies known to prolong life.3-6 Pain responses are valuable, particularly if durable, and patient-reported outcomes are certainly helpful, but these outcomes are highly subjective, hard to quantify across a trial, and heterogeneous and dependent on baseline symptoms.4,7 Technetium-99 methylene diphosphonate bone scans have traditionally been used to quantify progression in bone, but this nuclear tracer only indirectly measures the tumor and instead more likely images osteoblastic activity in the tumor microenvironment. The problem of imaging bone metastases with traditional bone scans becomes apparent during the common observation of bone scan flare (new lesions seen during response) during treatment with novel hormonal therapies, such as abiraterone acetate or enzalutamide.8 In 2008, the Prostate Cancer Working group 2 (PCWG2) developed guidelines on the determination of progression in bone that sought to account for this initial healing reaction that can confuse the determination of progression versus response.9 These guidelines called for confirmatory scans to identify whether new lesions seen at the initial post-treatment bone scan were truly progression or were indicative of an initial successful response to therapy. Men with bone scan flare typically have a PSA decline and pain improvements but have new lesions observed as compared with pretreatment imaging. Responding men typically do not develop ongoing new bone lesions at their next follow-up bone scan. PCWG2 attempted to quantify this and defined bone scan progression as having two additional confirmed bone lesions over time for those men with two new lesions seen 1322
© 2015 by American Society of Clinical Oncology
at this first reassessment (the “2⫹2 rule”), or for time points beyond this first assessment, two new confirmed bone lesions over time.9 PCWG2 emphasized the need to maintain men on effective therapies and reduce this misclassification of progression, and these guidelines are incorporated into nearly every phase II and III trial in CRPC since their development.10 It is with this background that Morris et al11 publish their analysis of this PCWG2-defined radiographic progression-free survival (rPFS). In this study, rPFS was defined using a modified form of RECIST 1.0 for soft tissue lesions, in which only lymph nodes ⱖ 2 cm were considered measurable. Bone lesions were only considered on the basis of bone scan results using PCWG2 criteria and were ignored on CT/MRI RECIST scoring. Previous attempts at correlating PFS with the gold standard of overall survival using older definitions led to weak associations and a general lack of confidence in this end point.12,13 In the context of this phase III trial of abiraterone acetate and prednisone versus prednisone alone in chemotherapy-naive men with mCRPC, the investigators rigorously evaluated a bone scan assessment much like any biomarker for reliability, reproducibility, and for prognostic associations with overall survival. This article is a landmark analysis, as it provides validation for this modified definition of rPFS in this setting. There is widespread interest in employing surrogate end points such as rPFS to make timely decisions about the efficacy of certain drugs, as well-powered comparative trials with overall survival as the primary end point will become increasingly challenging given approvals of multiple new effective agents and lengthening survival. Morris et al11 reported several key findings. One, that there was general agreement between investigators and independent radiologists on progression (75% to 80%) in terms of the occurrence or timing of progression. This is critical because if agreement is weak, then the entire end point becomes questionable; establishing agreement provides an objective validation to the PCWG2 criteria that can be built on in future guidelines. Second, 15% to 20% of men experienced bone scan flare in the absence of confirmed bone scan progression over time. In the past, these men would have been removed from the trial as a result of progression, when in reality, they were likely experiencing a response-induced visualization of bone metastases without true progression. This improvement in misclassification may have contributed to the success of abiraterone acetate and enzalutamide, as awareness of bone scan flare led to patients staying on drug Journal of Clinical Oncology, Vol 33, No 12 (April 20), 2015: pp 1322-1324
Downloaded from jco.ascopubs.org on November 14, 2015. For personal use only. No other uses without permission. Copyright © 2015 American Society of Clinical Oncology. All rights reserved.
Editorial
longer and having a better chance for improved overall survival. Third, rPFS was associated with overall survival (OS), with about half of the variability in rPFS explaining the variability in OS. Older definitions of PFS demonstrated associations in the 30% range, suggesting that when early bone scan flare is accounted for, misclassification of progression is reduced. It is noteworthy that the association of rPFS with OS was strongest in the abiraterone treatment group, suggesting that accounting for bone scan flare differentially improved misclassification where flare is more likely to occur. Finally, this analysis provides data on how men with mCRPC treated with abiraterone acetate progress. Approximately 40% of men progress in bone only, 40% progress in soft tissue only, and 12% progress in both bone and soft tissue. Only 6% of men died before progression. Thus, in following men on novel hormonal therapy before the use of docetaxel chemotherapy or radium-223, CT or MRI scans are needed to image soft tissue and visceral progression, in addition to bone scans, and omitting one may miss important progression events that could trigger a change in therapy. Likewise, progression occurs in some men quickly, by only 8 to 12 weeks, and on average progression occurs around 14 to 16 months from treatment initiation, indicating the need for ongoing surveillance imaging even in responding men. Despite the positive findings from Morris et al,11 the clinical utility of rPFS is not yet established, and this analysis has several limitations. First is that surrogacy for overall survival was not established. We know that some therapies improve rPFS without a major impact on OS,14 some therapies improve OS without a major impact on rPFS,3 and of course some therapies improve both rPFS and OS.15-18 Abiraterone acetate improved both rPFS and OS to different degrees in this trial, but this is not always the case. Thus, the value of rPFS likely remains treatment and mechanism dependent.19 However, rPFS may still be a useful phase II end point to screen potentially active agents for phase III testing in some contexts. A second limitation is the lack of analysis of PSA changes in the context of rPFS. Given that abiraterone acetate can directly modulate AR activity and PSA production, it would be valuable to understand the relationship of early PSA declines with bone scan and soft tissue response and progression/flare, whether some men can forgo imaging safely based on a substantial PSA decline, and how best to define bone scan flare in the context of this and other biomarkers such as alkaline phosphatase.20 Finally, a more appropriate method to analyze the rPFS end point is an interval-censored approach. To use this method, all assessments of the rPFS composite end point should be measured at the same time interval. Often these assessments are not measured at the same time, as patients are frequently taken off study at progression by one criterion and the other end points are not measured and censored. The importance of tracking these end points in all patients is critical to determining whether a given end point is a surrogate. This analysis raises multiple questions for future studies. The first is the need to compile a range of trials using agents with a variety of mechanisms (hormonal, cytotoxic, immunologic, and so on) to examine whether trial-level surrogacy of overall survival can be achieved for rPFS. If surrogacy is achievable, it may only apply to certain contexts, for example.2 Second is the need to develop a composite definition of bone scan flare that accounts for the clinical and biomarker context in a given patient over time. Third is the need to validate these findings externally and in different treatment contexts (prechemowww.jco.org
therapy and postchemotherapy settings, castration-sensitive setting, nonmetastatic settings). Finally, there is a need to develop more automated and objective assessments of bone scan progression that further reduce variability and account for misclassification as a result of flare. For example, the bone scan index (BSI) may be a useful tool to quantify bone burden over time by quantifying the number of hot spots and area of normal bone taken up by disease.21 However, BSI itself must still account for new lesions and flare over time, it is still subject to the limitations inherent in different contexts and drug mechanisms, and a definition of BSI progression in prostate cancer is not yet established. Morris et al11 are to be congratulated for developing, evaluating, and clinically validating a new form of radiographic progression in a large clinical trial. A critical task remains, namely to validate the clinical utility of rPFS for capturing the overall survival benefit with different agents. Only then will we be closer to an intermediate approvable end point in mCRPC. A validated surrogate would be of tremendous benefit to patients and the health care system, allowing rapid assessments of new agents in this patient population and minimizing costs to research and society. AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
Disclosures provided by the authors are available with this article at www.jco.org. AUTHOR CONTRIBUTIONS
Administrative support: Andrew J. Armstrong Manuscript writing: All authors Final approval of manuscript: All authors REFERENCES 1. Eisenhauer EA, Therasse P, Bogaerts J, et al: New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1). Eur J Cancer 45:228-247, 2009 2. Armstrong AJ, Eisenberger MA, Halabi S, et al: Biomarkers in the management and treatment of men with metastatic castration-resistant prostate cancer. Eur Urol 61:549-559, 2012 3. Kantoff PW, Higano CS, Shore ND, et al: Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med 363:411-422, 2010 4. Armstrong AJ, Garrett-Mayer E, Ou Yang YC, et al: Prostate-specific antigen and pain surrogacy analysis in metastatic hormone-refractory prostate cancer. J Clin Oncol 25:3965-3970, 2007 5. Petrylak DP, Ankerst DP, Jiang CS, et al: Evaluation of prostate-specific antigen declines for surrogacy in patients treated on SWOG 99-16. J Natl Cancer Inst 98:516-521, 2006 6. Halabi S, Armstrong AJ, Sartor O, et al: Prostate-specific antigen changes as surrogate of overall survival (OS) in men with metastatic castration-resistant prostate cancer (mCRPC) treated with second line chemotherapy. J Clin Oncol 31:3944-3950, 2003 7. Halabi S, Vogelzang NJ, Kornblith AB, et al: Pain predicts overall survival in men with metastatic castration-refractory prostate cancer. J Clin Oncol 26:25442549, 2008 8. Ryan CJ, Shah SK, Efstathiou E, et al: Phase II study of abiraterone acetate in chemotherapy-naive metastatic castration-resistant prostate cancer displaying bone flare discordant with serologic response. Clin Cancer Res 17:4854-4861, 2011 9. Scher HI, Halabi S, Tannock I, et al: Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: Recommendations of the Prostate Cancer Clinical Trials Working Group. J Clin Oncol 26:1148-1159, 2008 10. Scher HI, Morris MJ, Basch E, et al: End points and outcomes in castration-resistant prostate cancer: From clinical trials to clinical practice. J Clin Oncol 29:3695-3704, 2011 11. Morris MJ, Molina A, Small EJ, et al: Radiographic progression-free survival as a response biomarker in metastatic castration-resistant prostate cancer: COU-AA-302 results. J Clin Oncol 33:1356-1363, 2015
© 2015 by American Society of Clinical Oncology
Downloaded from jco.ascopubs.org on November 14, 2015. For personal use only. No other uses without permission. Copyright © 2015 American Society of Clinical Oncology. All rights reserved.
1323
Editorial
12. Halabi S, Vogelzang NJ, Ou SS, et al: Progression-free survival as a predictor of overall survival in men with castrate-resistant prostate cancer. J Clin Oncol 27:2766-2771, 2009 13. Scher HI, Warren M, Heller G: The association between measures of progression and survival in castrate-metastatic prostate cancer. Clin Cancer Res 13:1488-1492, 2007 14. Kelly WK, Halabi S, Carducci MA, et al: A randomized, double-blind, placebo-controlled phase III trial comparing docetaxel, prednisone, and placebo with docetaxel, prednisone, and bevacizumab in men with metastatic castrationresistant prostate cancer (mCRPC): Survival results of CALGB 90401. J Clin Oncol 28:344s, 2010 (suppl; abstr LBA4511) 15. Beer TM, Armstrong AJ, Rathkopf DE, et al: Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med 372:1755-1756, 2014 16. de Bono JS, Oudard S, Ozguroglu M, et al: Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: A randomised open-label trial. Lancet 376:1147-1154, 2010
17. Ryan CJ, Smith MR, de Bono JS, et al: Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med 368:138-148, 2013 18. Tannock IF, de WR, Berry WR, et al: Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med 351:1502-1512, 2004 19. Hoos A, Eggermont AM, Janetzki S, et al: Improved endpoints for cancer immunotherapy trials. J Natl Cancer Inst 102:1388-1397, 2010 20. Sonpavde G, Pond GR, Berry WR, et al: Serum alkaline phosphatase changes predict survival independent of PSA changes in men with castrationresistant prostate cancer and bone metastasis receiving chemotherapy. Urol Oncol 117:3963-3971, 2010 21. Armstrong AJ, Kaboteh R, Carducci MA, et al: Assessment of the bone scan index in a randomized placebo-controlled trial of tasquinimod in men with metastatic castration-resistant prostate cancer (mCRPC). Urol Oncol 32:1308-1316, 2014
DOI: 10.1200/JCO.2014.59.4283; published online ahead of print at www.jco.org on February 9, 2015
■ ■ ■
Simplify Your Search With JCO Subject Collections Subject Collections are topic-specific archives of articles published on jco.org that make it easy for you to find the research you need. Instead of random, time-consuming keyword searches, JCO Subject Collections allow you to quickly browse your interest areas for articles on specific diseases and treatments. Best of all, by signing up for Collection Alerts, you’ll receive e-mail notification whenever JCO publishes an article in your interest area. Sign up today at jco.org/collections.
1324
© 2015 by American Society of Clinical Oncology
JOURNAL OF CLINICAL ONCOLOGY
Downloaded from jco.ascopubs.org on November 14, 2015. For personal use only. No other uses without permission. Copyright © 2015 American Society of Clinical Oncology. All rights reserved.
Editorial
AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
Making Progress on Progression in Metastatic Prostate Cancer The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I ⫽ Immediate Family Member, Inst ⫽ My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO’s conflict of interest policy, please refer to www.asco.org/rwc or jco.ascopubs.org/site/ifc. Andrew J. Armstrong Consulting or Advisory Role: Janssen Oncology, Medivation/Astellas, sanofi-aventis, Bayer, Dendreon Speakers’ Bureau: Dendreon Research Funding: Dendreon (Inst), Medivation (Inst), Janssen (Inst), sanofi-aventis (Inst), Bayer (Inst)
www.jco.org
Travel, Accommodations, Expenses: Janssen, Medivation, Dendreon, Bayer Susan Halabi Research Funding: sanofi-aventis (Inst)
© 2015 by American Society of Clinical Oncology
Downloaded from jco.ascopubs.org on November 14, 2015. For personal use only. No other uses without permission. Copyright © 2015 American Society of Clinical Oncology. All rights reserved.
33
䡠
NUMBER
12
䡠
APRIL
20
2015
JOURNAL OF CLINICAL ONCOLOGY
E
D
I
T
O
R
I
A
L
Making Progress on Progression in Metastatic Prostate Cancer Andrew J. Armstrong, Duke Cancer Institute, Duke University, Durham, NC Susan Halabi, Alliance Statistics and Data Center, Duke University, Durham, NC See accompanying articles on page 1348 and 1356
Determining clinical benefit to therapy is among the most critical aspects of oncology care. At the individual level, this determination influences cessation or continuation of therapy and can dramatically affect patient and family perceptions of hope and optimism. At the trial level, these determinations affect regulatory approvals, optimal care delivery, and the chance of a therapy reaching the clinic. In men with metastatic castration-resistant prostate cancer (CRPC), a number of challenges exist in assessing clinical benefit to therapies. First, the vast majority of men have metastatic disease confined predominantly to bone, making response challenging to assess using traditional RECIST criteria1 that were developed for other cancer types. Second, prostate-specific antigen (PSA) as a marker of response may be valuable in some contexts such as with androgen-receptor directed therapies,2 but in other settings, PSA may not drop to arbitrary degrees despite the use of chemotherapies or immunotherapies known to prolong life.3-6 Pain responses are valuable, particularly if durable, and patient-reported outcomes are certainly helpful, but these outcomes are highly subjective, hard to quantify across a trial, and heterogeneous and dependent on baseline symptoms.4,7 Technetium-99 methylene diphosphonate bone scans have traditionally been used to quantify progression in bone, but this nuclear tracer only indirectly measures the tumor and instead more likely images osteoblastic activity in the tumor microenvironment. The problem of imaging bone metastases with traditional bone scans becomes apparent during the common observation of bone scan flare (new lesions seen during response) during treatment with novel hormonal therapies, such as abiraterone acetate or enzalutamide.8 In 2008, the Prostate Cancer Working group 2 (PCWG2) developed guidelines on the determination of progression in bone that sought to account for this initial healing reaction that can confuse the determination of progression versus response.9 These guidelines called for confirmatory scans to identify whether new lesions seen at the initial post-treatment bone scan were truly progression or were indicative of an initial successful response to therapy. Men with bone scan flare typically have a PSA decline and pain improvements but have new lesions observed as compared with pretreatment imaging. Responding men typically do not develop ongoing new bone lesions at their next follow-up bone scan. PCWG2 attempted to quantify this and defined bone scan progression as having two additional confirmed bone lesions over time for those men with two new lesions seen 1322
© 2015 by American Society of Clinical Oncology
at this first reassessment (the “2⫹2 rule”), or for time points beyond this first assessment, two new confirmed bone lesions over time.9 PCWG2 emphasized the need to maintain men on effective therapies and reduce this misclassification of progression, and these guidelines are incorporated into nearly every phase II and III trial in CRPC since their development.10 It is with this background that Morris et al11 publish their analysis of this PCWG2-defined radiographic progression-free survival (rPFS). In this study, rPFS was defined using a modified form of RECIST 1.0 for soft tissue lesions, in which only lymph nodes ⱖ 2 cm were considered measurable. Bone lesions were only considered on the basis of bone scan results using PCWG2 criteria and were ignored on CT/MRI RECIST scoring. Previous attempts at correlating PFS with the gold standard of overall survival using older definitions led to weak associations and a general lack of confidence in this end point.12,13 In the context of this phase III trial of abiraterone acetate and prednisone versus prednisone alone in chemotherapy-naive men with mCRPC, the investigators rigorously evaluated a bone scan assessment much like any biomarker for reliability, reproducibility, and for prognostic associations with overall survival. This article is a landmark analysis, as it provides validation for this modified definition of rPFS in this setting. There is widespread interest in employing surrogate end points such as rPFS to make timely decisions about the efficacy of certain drugs, as well-powered comparative trials with overall survival as the primary end point will become increasingly challenging given approvals of multiple new effective agents and lengthening survival. Morris et al11 reported several key findings. One, that there was general agreement between investigators and independent radiologists on progression (75% to 80%) in terms of the occurrence or timing of progression. This is critical because if agreement is weak, then the entire end point becomes questionable; establishing agreement provides an objective validation to the PCWG2 criteria that can be built on in future guidelines. Second, 15% to 20% of men experienced bone scan flare in the absence of confirmed bone scan progression over time. In the past, these men would have been removed from the trial as a result of progression, when in reality, they were likely experiencing a response-induced visualization of bone metastases without true progression. This improvement in misclassification may have contributed to the success of abiraterone acetate and enzalutamide, as awareness of bone scan flare led to patients staying on drug Journal of Clinical Oncology, Vol 33, No 12 (April 20), 2015: pp 1322-1324
Downloaded from jco.ascopubs.org on November 14, 2015. For personal use only. No other uses without permission. Copyright © 2015 American Society of Clinical Oncology. All rights reserved.
Editorial
longer and having a better chance for improved overall survival. Third, rPFS was associated with overall survival (OS), with about half of the variability in rPFS explaining the variability in OS. Older definitions of PFS demonstrated associations in the 30% range, suggesting that when early bone scan flare is accounted for, misclassification of progression is reduced. It is noteworthy that the association of rPFS with OS was strongest in the abiraterone treatment group, suggesting that accounting for bone scan flare differentially improved misclassification where flare is more likely to occur. Finally, this analysis provides data on how men with mCRPC treated with abiraterone acetate progress. Approximately 40% of men progress in bone only, 40% progress in soft tissue only, and 12% progress in both bone and soft tissue. Only 6% of men died before progression. Thus, in following men on novel hormonal therapy before the use of docetaxel chemotherapy or radium-223, CT or MRI scans are needed to image soft tissue and visceral progression, in addition to bone scans, and omitting one may miss important progression events that could trigger a change in therapy. Likewise, progression occurs in some men quickly, by only 8 to 12 weeks, and on average progression occurs around 14 to 16 months from treatment initiation, indicating the need for ongoing surveillance imaging even in responding men. Despite the positive findings from Morris et al,11 the clinical utility of rPFS is not yet established, and this analysis has several limitations. First is that surrogacy for overall survival was not established. We know that some therapies improve rPFS without a major impact on OS,14 some therapies improve OS without a major impact on rPFS,3 and of course some therapies improve both rPFS and OS.15-18 Abiraterone acetate improved both rPFS and OS to different degrees in this trial, but this is not always the case. Thus, the value of rPFS likely remains treatment and mechanism dependent.19 However, rPFS may still be a useful phase II end point to screen potentially active agents for phase III testing in some contexts. A second limitation is the lack of analysis of PSA changes in the context of rPFS. Given that abiraterone acetate can directly modulate AR activity and PSA production, it would be valuable to understand the relationship of early PSA declines with bone scan and soft tissue response and progression/flare, whether some men can forgo imaging safely based on a substantial PSA decline, and how best to define bone scan flare in the context of this and other biomarkers such as alkaline phosphatase.20 Finally, a more appropriate method to analyze the rPFS end point is an interval-censored approach. To use this method, all assessments of the rPFS composite end point should be measured at the same time interval. Often these assessments are not measured at the same time, as patients are frequently taken off study at progression by one criterion and the other end points are not measured and censored. The importance of tracking these end points in all patients is critical to determining whether a given end point is a surrogate. This analysis raises multiple questions for future studies. The first is the need to compile a range of trials using agents with a variety of mechanisms (hormonal, cytotoxic, immunologic, and so on) to examine whether trial-level surrogacy of overall survival can be achieved for rPFS. If surrogacy is achievable, it may only apply to certain contexts, for example.2 Second is the need to develop a composite definition of bone scan flare that accounts for the clinical and biomarker context in a given patient over time. Third is the need to validate these findings externally and in different treatment contexts (prechemowww.jco.org
therapy and postchemotherapy settings, castration-sensitive setting, nonmetastatic settings). Finally, there is a need to develop more automated and objective assessments of bone scan progression that further reduce variability and account for misclassification as a result of flare. For example, the bone scan index (BSI) may be a useful tool to quantify bone burden over time by quantifying the number of hot spots and area of normal bone taken up by disease.21 However, BSI itself must still account for new lesions and flare over time, it is still subject to the limitations inherent in different contexts and drug mechanisms, and a definition of BSI progression in prostate cancer is not yet established. Morris et al11 are to be congratulated for developing, evaluating, and clinically validating a new form of radiographic progression in a large clinical trial. A critical task remains, namely to validate the clinical utility of rPFS for capturing the overall survival benefit with different agents. Only then will we be closer to an intermediate approvable end point in mCRPC. A validated surrogate would be of tremendous benefit to patients and the health care system, allowing rapid assessments of new agents in this patient population and minimizing costs to research and society. AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
Disclosures provided by the authors are available with this article at www.jco.org. AUTHOR CONTRIBUTIONS
Administrative support: Andrew J. Armstrong Manuscript writing: All authors Final approval of manuscript: All authors REFERENCES 1. Eisenhauer EA, Therasse P, Bogaerts J, et al: New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1). Eur J Cancer 45:228-247, 2009 2. Armstrong AJ, Eisenberger MA, Halabi S, et al: Biomarkers in the management and treatment of men with metastatic castration-resistant prostate cancer. Eur Urol 61:549-559, 2012 3. Kantoff PW, Higano CS, Shore ND, et al: Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med 363:411-422, 2010 4. Armstrong AJ, Garrett-Mayer E, Ou Yang YC, et al: Prostate-specific antigen and pain surrogacy analysis in metastatic hormone-refractory prostate cancer. J Clin Oncol 25:3965-3970, 2007 5. Petrylak DP, Ankerst DP, Jiang CS, et al: Evaluation of prostate-specific antigen declines for surrogacy in patients treated on SWOG 99-16. J Natl Cancer Inst 98:516-521, 2006 6. Halabi S, Armstrong AJ, Sartor O, et al: Prostate-specific antigen changes as surrogate of overall survival (OS) in men with metastatic castration-resistant prostate cancer (mCRPC) treated with second line chemotherapy. J Clin Oncol 31:3944-3950, 2003 7. Halabi S, Vogelzang NJ, Kornblith AB, et al: Pain predicts overall survival in men with metastatic castration-refractory prostate cancer. J Clin Oncol 26:25442549, 2008 8. Ryan CJ, Shah SK, Efstathiou E, et al: Phase II study of abiraterone acetate in chemotherapy-naive metastatic castration-resistant prostate cancer displaying bone flare discordant with serologic response. Clin Cancer Res 17:4854-4861, 2011 9. Scher HI, Halabi S, Tannock I, et al: Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: Recommendations of the Prostate Cancer Clinical Trials Working Group. J Clin Oncol 26:1148-1159, 2008 10. Scher HI, Morris MJ, Basch E, et al: End points and outcomes in castration-resistant prostate cancer: From clinical trials to clinical practice. J Clin Oncol 29:3695-3704, 2011 11. Morris MJ, Molina A, Small EJ, et al: Radiographic progression-free survival as a response biomarker in metastatic castration-resistant prostate cancer: COU-AA-302 results. J Clin Oncol 33:1356-1363, 2015
© 2015 by American Society of Clinical Oncology
Downloaded from jco.ascopubs.org on November 14, 2015. For personal use only. No other uses without permission. Copyright © 2015 American Society of Clinical Oncology. All rights reserved.
1323
Editorial
12. Halabi S, Vogelzang NJ, Ou SS, et al: Progression-free survival as a predictor of overall survival in men with castrate-resistant prostate cancer. J Clin Oncol 27:2766-2771, 2009 13. Scher HI, Warren M, Heller G: The association between measures of progression and survival in castrate-metastatic prostate cancer. Clin Cancer Res 13:1488-1492, 2007 14. Kelly WK, Halabi S, Carducci MA, et al: A randomized, double-blind, placebo-controlled phase III trial comparing docetaxel, prednisone, and placebo with docetaxel, prednisone, and bevacizumab in men with metastatic castrationresistant prostate cancer (mCRPC): Survival results of CALGB 90401. J Clin Oncol 28:344s, 2010 (suppl; abstr LBA4511) 15. Beer TM, Armstrong AJ, Rathkopf DE, et al: Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med 372:1755-1756, 2014 16. de Bono JS, Oudard S, Ozguroglu M, et al: Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: A randomised open-label trial. Lancet 376:1147-1154, 2010
17. Ryan CJ, Smith MR, de Bono JS, et al: Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med 368:138-148, 2013 18. Tannock IF, de WR, Berry WR, et al: Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med 351:1502-1512, 2004 19. Hoos A, Eggermont AM, Janetzki S, et al: Improved endpoints for cancer immunotherapy trials. J Natl Cancer Inst 102:1388-1397, 2010 20. Sonpavde G, Pond GR, Berry WR, et al: Serum alkaline phosphatase changes predict survival independent of PSA changes in men with castrationresistant prostate cancer and bone metastasis receiving chemotherapy. Urol Oncol 117:3963-3971, 2010 21. Armstrong AJ, Kaboteh R, Carducci MA, et al: Assessment of the bone scan index in a randomized placebo-controlled trial of tasquinimod in men with metastatic castration-resistant prostate cancer (mCRPC). Urol Oncol 32:1308-1316, 2014
DOI: 10.1200/JCO.2014.59.4283; published online ahead of print at www.jco.org on February 9, 2015
■ ■ ■
Simplify Your Search With JCO Subject Collections Subject Collections are topic-specific archives of articles published on jco.org that make it easy for you to find the research you need. Instead of random, time-consuming keyword searches, JCO Subject Collections allow you to quickly browse your interest areas for articles on specific diseases and treatments. Best of all, by signing up for Collection Alerts, you’ll receive e-mail notification whenever JCO publishes an article in your interest area. Sign up today at jco.org/collections.
1324
© 2015 by American Society of Clinical Oncology
JOURNAL OF CLINICAL ONCOLOGY
Downloaded from jco.ascopubs.org on November 14, 2015. For personal use only. No other uses without permission. Copyright © 2015 American Society of Clinical Oncology. All rights reserved.
Editorial
AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
Making Progress on Progression in Metastatic Prostate Cancer The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I ⫽ Immediate Family Member, Inst ⫽ My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO’s conflict of interest policy, please refer to www.asco.org/rwc or jco.ascopubs.org/site/ifc. Andrew J. Armstrong Consulting or Advisory Role: Janssen Oncology, Medivation/Astellas, sanofi-aventis, Bayer, Dendreon Speakers’ Bureau: Dendreon Research Funding: Dendreon (Inst), Medivation (Inst), Janssen (Inst), sanofi-aventis (Inst), Bayer (Inst)
www.jco.org
Travel, Accommodations, Expenses: Janssen, Medivation, Dendreon, Bayer Susan Halabi Research Funding: sanofi-aventis (Inst)
© 2015 by American Society of Clinical Oncology
Downloaded from jco.ascopubs.org on November 14, 2015. For personal use only. No other uses without permission. Copyright © 2015 American Society of Clinical Oncology. All rights reserved.
