Radiation Plus Intermittent Hormone Therapy Improves PFS in Oligometastatic Prostate Cancer

Chad Tang, MD

A regimen comprised of radiation and intermittent hormone therapy (HT) resulted in an improvement in progression-free survival (PFS), time off HT, and time with eugonad testosterone in patients with oligometastatic prostate cancer, according to data from the phase 2 EXTEND trial (NCT03599765) presented during the 2022 ASTRO Annual Meeting.¹

At a median follow-up of 22.1 months, the median PFS had not yet been reached in those who received combined treatment (n = 43) vs 15.8 months in those who were given HT alone (n = 44), translating to a 75% reduction in the risk of disease progression or death (HR, 0.25; 95% CI, 0.12-0.55; stratified log-rank P < .001).¹

Moreover, fewer patients who received combined treatment had new lesions 2 years following treatment than those who received HT alone, at 33% and 41%, respectively (P = .004).² Those in the combination arm also experienced normal testosterone levels for a longer duration than those who just received HT (P = .03).²

“Using radiation for oligometastatic prostate cancer can result in excellent tumor control and good long-term outcomes, and it may allow us to give these patients long breaks from HT,” Chad Tang, MD, lead study author and an associate professor of radiation oncology at The University of Texas MD Anderson Cancer Center in Houston, Texas, stated in a press release.²

HT synergizes with radiation therapy when used in the treatment of patients with prostate cancer, and when administered up front, it has been linked with survival improvements. Despite these benefits, this approach is known to have significant toxicities that can affect how patients look, their thoughts and feelings, sexual function, and muscle and bone. HT can also result in significant long-term adverse effects, like obesity, increased risk of cardiovascular disease and stroke, and increased risk of diabetes.¹

Data from the phase 3 SWOG S9346 trial (NCT00002651) showed that intermittent HT (n = 770) was noninferior to continuous HT (n = 765) in patients with metastatic prostate cancer (n = 1535).³ The median prostate-specific antigen (PSA) at the time of diagnosis in these patients was 42 (interquartile range, 15-132), and the PSA following 7 months of HT was greater than 0.2 in 65% of patients. During breaks of HT, the therapy was resumed when PSA was at 20 or higher.³

The phase 2 EXTEND basket trial enrolled adult patients with up to 5 metastases from several types of solid tumors. At the meeting, Dr Tang shared data from the primary analysis of the prostate basket, which comprised 87 patients who were on intermittent HT for their disease.²

Study participants were randomly assigned to receive 6 months of HT plus local therapy or 6 months of HT alone. Local therapy could have included radiation, surgery, or cryotherapy to all sites of oligometastatic disease; all received radiation treatment.^1,2 

Moreover, participants received hormone therapy for at least 2 months prior to starting the trial. Each patient stopped HT for a planned break of 6 months following study start. Upon disease progression, participants on both arms resumed HT.²

Stratification factors comprised number of metastatic lesions (1 to 2 vs 3 to 5), number of previous lines of systemic therapy (0 to 1 vs more than 1), whether second-generation HT was received (yes vs no), and duration of prior HT (less than 3 months vs 3 months or more).¹

The primary end point was PFS. Investigators specifically looked at biochemical progression (≥2 ng/mL or ≥25% increase above nadir), clinical progression (symptoms or need to restart HT), radiographic progression by RECIST v1.1 criteria, and death.¹

Investigators also evaluated the immune-stimulating effects of radiation and reported increased T-cell activation.² They also observed signals indicative of greater immune activity in patients who received the combined approach vs those who did not.²

In terms of safety, three grade 3 adverse effects were reported in each arm.²

Tang added that the synergy between radiation and HT could be the key to the success observed with the combined approach.2 He concluded that this combined approach offers a way to maintain disease control and preserve quality of life in this patient population.

References

1. Tang C, Sherry AD, Haymaker C, et al. Addition of metastasis-directed therapy to intermittent hormone therapy for oligometastatic prostate cancer (EXTEND): a multicenter, randomized phase II trial. Presented at: 2022 ASTRO Annual Meeting; October 23-26, 2022; San Antonio, TX. Abstract LBA 05
2. Radiation-hormone therapy combination may slow growth of oligometastatic prostate cancer. News release. ASTRO. October 25, 2022. Accessed October 27, 2022. https://bit.ly/3W5wjii
3. Hussain M, Tangen CM, Berry DL, et al. Intermittent versus continuous androgen deprivation in prostate cancer. N Engl J Med. 2013;368(14):1314-1325. doi:10.1056/NEJMoa1212299