An update on the STOMP Trial.
STOMP is a small (Phase II) trial involving metastases-directed therapy [MDT] in men with oligometastatic disease (few mets - in this case, ≤3 on choline PET/CT at recurrence).
From 2014 [1]: "One of the goals of this approach is to delay the start of palliative androgen deprivation therapy (ADT), with its negative impact on quality of life."
"Patients with an oligometastatic recurrence, diagnosed on choline PET/CT after local treatment with curative intent, will be randomised in a 1:1 ratio between arm A: active surveillance only and arm B: MTD followed by active surveillance. Patients will be stratified according to the location of metastasis (node vs. bone metastases) and PSA doubling time (≤3 vs. > 3 months). Both surgery and SBRT are allowed as MDT. Active surveillance means 3-monthly PSA testing and re-imaging at PSA progression. The primary endpoint is ADT-free survival. ADT will be started in both arms at time of polymetastatic disease (>3 metastatic lesions), local progression or symptoms. The secondary endpoints include progression-free survival, quality of life, toxicity and prostate-cancer specific survival."
The update:
"Immediate treatment of limited metastatic recurrence of prostate cancer led to a fourfold improvement in the proportion of patients alive without androgen deprivation therapy (ADT) at 5 years, according to data reported here.
"The estimated 5-year ADT-free survival rate was 34% for treated patients and 8% for those who were followed with active surveillance. Metastasis-directed treatment (MDT) led to better ADT-free survival regardless of prostate-specific antigen doubling time or lymph node involvement. Immediate treatment also delayed the time to development of castration-resistant prostate cancer (CRPC). Overall survival (OS) rate was 80-90% in both groups.
"The results added to evidence that immediate treatment may delay progression and improve survival but cannot be considered definitive because predefined criteria for statistical significance were not met, Piet Ost, MD, of Ghent University in Belgium, said at the Genitourinary Cancers Symposium.
"This was a phase II screening trial, and these are initial, nondefinitive results," said Ost. "Any P-value below 0.20 is considered significant for this specific trial, but a significant result does not mean this type of trial will change practice. This trial was designed to show maybe what we should be doing in the next trial, a phase III trial."
"The findings came from the Belgium-based, multicenter STOMP trial involving men with metachronous oligorecurrent prostate cancer. The trial began in 2012, when the European Association of Urology (EAU) clinical guidelines dichotomized treatment recommendations for metastatic prostate cancer into symptomatic and asymptomatic. All patients with symptomatic disease received ADT, whereas clinicians had the option to offer asymptomatic patients either ADT or observation with delayed ADT until disease progression.
"STOMP limited enrollment to men with asymptomatic or minimally symptomatic metastatic recurrence (oligometastatic, one to three extracranial lesions identified by choline positron emission tomography/computed tomography). In keeping with EAU recommendations at the time, the investigators chose observation as the standard of care for the control arm. In the intervention arm, patients received immediate MDT. In both groups, treatment continued until development of symptomatic local or polymetastatic progression, when ADT was initiated.
"The trial had a primary endpoint of time to initiation of ADT (ADT-free survival). The researchers defined statistical significance for the trial as P=0.20, but only results associated with a P-value of <0.005 were considered definitive.
"The study included 62 patients, with a median follow-up of 5.3 years. Baseline characteristics and other details of the trial design have been reported previously.
"The primary analysis showed that immediate treatment led to a 43% reduction in the hazard for ADT-free survival (80% CI 0.38-0.84, P=0.06). A per-protocol analysis yielded a hazard ratio of 0.53 (80% CI 0.35-0.79, P=0.04). Subgroup analyses yielded hazard ratios of 0.41 for patients with a PSA doubling time of less than 3 months, 0.65 for those with a PSA doubling time of 3 or more months, 0.42 for patients with lymph-node involvement, and 0.74 for those without nodal involvement.
"CRPC-free survival (post-ADT) favored the intervention arm (HR 0.62, 80% CI 0.35-1.09), but the difference did not achieve the trial-defined level of statistical significance. A per-protocol analysis showed a 49% reduction in the hazard ratio (80% CI 0.29-0.90, P=0.12).
"Five-year OS was high in both groups, as was prostate cancer-specific survival, as only six of 14 total deaths resulted from prostate cancer, said Ost.
"Whether MDT will lead to improvement in "outcomes that matter" remains to be determined, Neha Vapiwala, MD, of the University of Pennsylvania in Philadelphia, said during a review that preceded Ost's presentation. Studies of stereotactic ablative radiotherapy (SABR) have yielded encouraging results, but trials to date had small numbers of patients and limited enrollment to patients with limited metastatic disease burden (generally one to three metastases).
"The previously reported primary results of the STOMP trial showed a median ADT-free survival of 21 months with MDT versus 13 months with surveillance. Vapiwala noted that metastatic progression was the principal reason for starting ADT in both treatment groups. Summarizing five recent studies involving about 350 patients total, she said half the patients had a solitary metastasis and nodal lesions accounted for about two thirds of the lesions versus one third for osseous lesions. Collectively, the studies showed a 2-year rate of freedom from systemic therapy of about 50%, accompanied by "promising gains in progression-free survival and distant metastasis-free survival."
"Multiple trials of MDT with SABR are ongoing, including several randomized trials and trials of combination therapy.
"The value of metastasis-directed therapy is really in the eyes of the beholder," Vapiwala said. "Whether the beholder is the patient, the provider, the insurer, or society is for us to answer as a group. We know that MDT is safe, feasible, and effective by a variety of important measures, but whether the outcomes -- such as ADT-free survival -- justify the intervention is an unanswered question."
"Regardless of your take on the value, MDT is happening," she added. "Let's hope we can do it in a way that is scientific and explore it in a responsible way."
-Patrick
Apalutamide for Metastatic Castration-Sensitive Prostate Cancer
