Phase III Trial Shows Improved Survival With Long‑Term Androgen-Deprivation Therapy Plus High-Dose Radiotherapy in Localized Prostate Cancer

“In the Spanish phase III DART01/05 GICOR trial reported in Lancet Oncology, Zapatero and colleagues found that long-term androgen-deprivation therapy (ADT) increased biochemical disease-free survival and overall survival vs short-term ADT when combined with high-dose radiotherapy in men with localized prostate cancer.

“In this open-label trial, 355 patients were randomly assigned between November 2005 and December  2010 to receive 4 months of ADT (n = 178) or 24 months of ADT (n = 177) following three-dimensional conformal radiotherapy at a minimum dose of 76 Gy (range, 76–82 Gy). Patients had to have clinical stage T1c–T3b, N0, M0 prostate adenocarcinoma with intermediate or high risk based on 2005 National Comprehensive Cancer Network criteria.

“The short-term ADT group received 4 months of neoadjuvant and concomitant androgen deprivation with subcutaenous goserelin (Zoladex) 2 months before and 2 months in combination with high-dose radiotherapy, with flutamide at 750 mg/d or bicalutamide at 50 mg/d added during the first 2 months of treatment. Patients in the long-term ADT group continued with the same luteinizing hormone–releasing hormone analog every 3 months for 24 months. The primary endpoint was biochemical disease-free survival on intention-to-treat analysis.”

Seeds Top EBRT as Boost Tx in Prostate Cancer

“Low-dose brachytherapy boosts held prostate cancer in check significantly better than dose-escalated external-beam radiation therapy (EBRT) in men with unfavorable-risk disease, a randomized trial showed.

“Patients treated with brachytherapy after androgen deprivation therapy (ADT) and whole-pelvis EBRT had an estimated 9-year relapse-free survival (RFS) 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, Scott Tyldesley, MD, of the British Columbia Cancer Agency in Vancouver, reported here at the Genitourinary Cancers Symposium.

” ‘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 GU toxicity with the low-dose rate boost, a 5% to 6% increase in the prevalence of late GU toxicity,’ he said.”

Maintenance Sunitinib Improved PFS in Extensive-Stage SCLC

“The use of maintenance sunitinib improved progression-free survival (PFS) over placebo among patients with untreated extensive-stage small-cell lung cancer (SCLC) in a new phase II study.

“ ‘Most of the 30,000 patients newly diagnosed each year with SCLC in the United States have extensive-stage disease,’ wrote study authors led by Neal E. Ready, MD, PhD, of Duke University Medical Center in Durham, North Carolina. ‘Despite achieving good disease control initially, patients with SCLC usually experience relapse within 6 months of first-line chemotherapy and often do not respond to subsequent chemotherapy.’

“In previous studies, maintenance chemotherapy after standard platinum-based therapy did not show any overall survival benefit. The new study aimed to test whether sunitinib, a small-molecule tyrosine kinase inhibitor that inhibits VEGF receptors and other targets. Results of the new study were published online ahead of print in the Journal of Clinical Oncology.

“The study enrolled a total of 144 patients, 49 of whom progressed or did not complete induction chemotherapy; 95 patients were randomly assigned to a placebo maintenance therapy group (46 patients) or a sunitinib maintenance therapy group (49 patients), and five patients on each arm did not receive the maintenance therapy. Sunitinib patients received 37.5 mg per day until progression.”

ADT Plus Docetaxel for Prostate Ca: Home Run or Foul Ball?

“A ‘home run’ in advanced prostate cancer did not clear the fence in a second evaluation of androgen deprivation therapy (ADT) with docetaxel, according to a study reported here.

“An updated analysis of a French study showed that adding chemotherapy to ADT did not significantly improve overall survival for men with hormone-sensitive, metastatic prostate cancer. However, the 13-month difference in favor of the docetaxel arm was comparable to the statistically significant 14-month improvement observed in a larger U.S. trial reported last year.

“The French study also failed to show a survival benefit in patients with high-volume disease, which accounted for two-thirds of the patients in the U.S. trial.

” ‘We are awaiting the analysis of [a third randomized trial], and we hope to come up with a common analysis of the three studies altogether in order to give the good [best] treatment for the good [best] patient,’ Gwenaelle Gravis, MD, of Institut Paoli-Calmettes in Marseilles, France, said here at the Genitourinary Cancers Symposium.

“For more than 40 years, ADT has represented standard of care for metastatic hormone-sensitive advanced prostate cancer. The emergence of effective chemotherapy for castration-resistant prostate cancer led to speculation that use of cytotoxic therapy in hormone-sensitive advanced prostate cancer might improve outcomes as compared with ADT alone.”

Improved Survival for Patients with Brain Mets Who Are 50 and Younger and Receive SRS Alone

“Cancer patients with limited brain metastases (one to four tumors) who are 50 years old and younger should receive stereotactic radiosurgery (SRS) without whole brain radiation therapy (WBRT), according to a study available online, open-access, and published in the March 15, 2015 issue of the International Journal of Radiation Oncology * Biology * Physics (Red Journal), the official scientific journal of the American Society for Radiation Oncology (ASTRO). For patients 50 years old and younger who received SRS alone, survival was improved by 13 percentage points when compared to those patients 50 years old and younger who received both SRS and WBRT.

“This study, ‘Phase 3 Trials of Stereotactic Radiation Surgery With or Without Whole-Brain Radiation Therapy For 1 to 4 Brain Metastases: Individual Patient Data Meta-Analysis,’ analyzed patient data from the three largest randomized clinical trials (RCT) of SRS and WBRT conducted to-date: the Asian trial (JROSG99-1) by Aoyama et al.[1], published in 2006; the North American trial (MDACC NCT00548756) by Chang et al.[2], published in 2009; and the European trial (EORTC 22952-26001) by Kocher et al.[3], published in 2011. A total of 364 patients from the three RCTs were evaluated for this meta-analysis. Of those 364 patients, 51 percent (186) were treated with SRS alone, and 49 percent (178) received both SRS and WBRT. Nineteen percent of patients (68) were 50 years old and younger, and 61 percent (19) of these patients had a single brain metastasis. Twenty percent of all patients (72) had local brain failure, which is the occurrence of progression of previously treated brain metastases; and 43 percent (156) experienced distant brain failure, which is the occurrence of new brain metastases in areas of the brain outside the primary tumor site(s).

“The impact of age on treatment effectiveness revealed SRS alone yielded improved overall survival (OS) in patients 50 years old and younger. Patients 50 years old and younger who received SRS alone had a median survival of 13.6 months after treatment, a 65 percent improvement, as opposed to 8.2 months for patients 50 years old and younger who were treated with SRS plus WBRT. Patients >50 years old had a median survival of 10.1 months when treated with SRS alone, and 8.6 months for those who received SRS plus WBRT.”

High-Dose Radiotherapy Fails to Improve Prostate Cancer Survival

“A high-dose radiotherapy schedule did not improve overall survival (OS) compared with the standard dose in men with stage II localized prostate cancer. But, local disease control and rates of distant metastasis were improved.

“After a median follow-up of 7 years, the 5-year OS rates were 88% and 89% in the high-dose and standard radiotherapy arms, and the 10-year OS rates were 67% and 66% in the high-dose and standard arms, respectively (P = .87).

“The results (Abstract 4) of the Radiation Therapy Oncology Group (RTOG) 0126 phase III trial were presented by Jeff M. Michalski, MD, of Washington University School of Medicine in St. Louis, at the 2015 Genitourinary Cancers Symposium.

“ ‘Disappointingly, we did not see an improvement in OS as we had hoped,’ Michalski told Cancer Network. ‘Dose escalation did not significantly decrease the rate of death from prostate cancer.’ ”

Provenge Induces Sustained Immune Response Even at 2 Years after Treatment

“Preliminary results from the phase II STAND trial have demonstrated a robust immune response with sipuleucel-T (Provenge) that continues 2 years after completing treatment in men with biochemically recurrent prostate cancer. The findings, along with data from an ongoing phase IV registry related to increasing enrollment of African Americans in prostate cancer trials, are being presented at the 2015 Genitourinary Cancers Symposium, held February 26 to 28 in Orlando…

“The STAND study (Abstract 171) is a randomized, phase II trial that consisted of two patient study groups. One group completed sipuleucel-T 2 weeks before initiation of androgen-deprivation therapy, and the second received the drug 3 months after the start of androgen-deprivation therapy. Preliminary results from STAND indicate that immune responses were observed in both study arms and suggest there may be a greater cellular immune response in patients who received sipuleucel-T prior to androgen-deprivation therapy. Humoral immune responses were observed and similar between both treatment arms.

“ ‘It is very encouraging to observe that [sipuleucel-T] provides an immune response in men with biochemical-recurrent prostate cancer long after the course of androgen deprivation therapy has ended,’ said Neal Shore, MD, Medical Director at the Carolina Urologic Research Center. ‘This study may also provide guidance on the optimal sequencing of immunotherapy and androgen-deprivation therapy in biochemical-recurrent prostate cancer.’ ”

Progenics Pharmaceuticals Presents Positive Phase 2 Data for PSMA ADC in Metastatic Castration-Resistant Prostate Cancer

“Progenics Pharmaceuticals, Inc., (Nasdaq:PGNX) today announced the presentation of the full results from its Phase 2 clinical study of PSMA ADC in patients with metastatic castration-resistant prostate cancer (mCRPC), including new data from the recently completed chemo-naïve cohort. The data was presented in a poster session and was also selected for inclusion in the ASCO GU Audio Poster Tour at the American Society of Clinical Oncology Genitourinary Cancers (ASCO GU) Symposium, taking place from February 26 – 28, 2015 in Orlando, Florida.

” ‘The full data from this trial provides compelling evidence of the anti-cancer properties of PSMA ADC, with both the surrogate biomarker and radiological data suggesting a meaningful clinical benefit in progressive metastatic castration-resistant prostate cancer,’ stated Daniel Petrylak, M.D., Professor of Medical Oncology at Yale Cancer Center, Clinical Research Program Leader for the Prostate and Urologic Cancers Program at Smilow Cancer Hospital at Yale-New Haven, and lead investigator on the trial.

” ‘Although advances in androgen deprivation therapy, or ADT, have provided great benefit to prostate cancer patients, treatment options when ADT fails remain limited, which is why the results for PSMA ADC in this patient population are so encouraging. We observed shrinkage of patients’ tumors, the conversion of unfavorable levels of circulating tumor cells to favorable levels and the reduction in patients’ PSA scores, all of which provide strong evidence of PSMA ADC anti-tumor activity,’ said Mark Baker, CEO of Progenics.”

Blood Samples as Surrogates for Tumor Biopsies in Patients with Lung Cancer

“A study examined the feasibility of using circulating free DNA (cfDNA) from blood samples of patients with advanced non-small-cell lung cancer as a surrogate for tumor biopsies to determine tumor-causing epidermal growth factor receptor (EGFR) mutations and then correlate that with expected patient outcomes, according to a study published online by JAMA Oncology.

“The analysis was a secondary objective of the EURTAC trial, which demonstrated the efficacy of erlotinib compared with standard chemotherapy for the first-line treatment of European patients with advanced non-small-cell lung cancer (NSCLC) with oncogenic EGFR mutations (exon 19 deletion or L858R mutations in exon 21) in tumor tissue.

“Rafael Rosell, M.D., of the Hospital Germans Trias I Pujol, Badalona, Spain, and coauthors examined EGFR mutations in cfDNA isolated from 97 baseline blood samples.

“Results show that in 76 samples from 97 (78 percent) patients, EGFR mutations in cfDNA were detected. Median overall survival was shorter in patients with the L858R mutation in cfDNA than in those with the exon 19 deletion (13.7 vs. 30 months). For patients with the L858R mutation in tissue, median overall survival was 13.7 months for patients with the L858R mutation in cfDNA and 27.7 months for those in whom the mutation was not detected in cfDNA. For the 76 patients with EGFR mutations in cfDNA, only erlotinib treatment was an independent predictor of longer disease progression-free survival.”