Stereotactic Ablative Radiotherapy for Oligoprogressive Cancers: Results of the Randomized Phase II STOP Trial.

This trial examined if patients with ≤5 sites of oligoprogression benefit from the addition of stereotactic ablative radiotherapy (SABR) to standard of care (SOC) systemic therapy. We enrolled patients with 1-5 metastases progressing on systemic therapy, and after stratifying by type of systemic therapy (cytotoxic vs. non-cytotoxic), randomized 1:2 between continued SOC treatment vs. SABR to all progressing lesions plus SOC. The trial was initially limited to non-small cell lung cancer but was expanded to include all non-hematologic malignancies to meet accrual goals. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), lesional control, quality of life, adverse events (AEs), and duration of systemic therapy post-randomization. Ninety patients with 127 oligoprogressive metastases were enrolled across 8 Canadian institutions, with 59 randomized to SABR and 31 to SOC. Median age was 67 years and 39 (43%) were female. The most common primary sites were lung (44%), genitourinary (23%) and breast (13%). Protocol adherence in the SOC arm was suboptimal, with 11 patients (35%) either receiving high-dose/ablative therapies (conflicting with trial protocol) or withdrawing from the study. Median follow-up was 31 months. There was no difference in PFS between arms (median PFS 8.4 months in the SABR arm vs. 4.3 months in the SOC arm but curves cross and 2-year PFS was 9% vs. 24% respectively, p=0.91). Median OS was 31.2 months vs. 27.4 months, respectively (p=0.22). Lesional control was superior with SABR (70% vs. 38% respectively, p=0.0015). There were 2 (3.4%) grade 3 and no grade 4/5 AEs attributable to SABR. SABR was well-tolerated with superior lesional control but did not improve PFS or OS. Accrual to this study was difficult, and the results may have been impacted by an unwillingness to forgo ablative treatments on the SOC arm. (NCT02756793).

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Déclaration de conflit d'intérêts

Declaration of competing interest Devin Schellenberg has received grants and honoraria from AstraZeneca and honoraria from Merck and Boehringer-Ingleheim, unrelated to the current study. Zsolt Gabos has received honoraria for advisory board and speaking engagements from AstraZeneca, unrelated to the current study. Meredith E. Giuliani reports participation in advisory boards for AstraZeneca and Bristol Myers Squibb, unrelated to the current study. Benjamin H. Lok reports research grants from Pfizer, and research grants, honoraria, and non-financial support from AstraZeneca, unrelated to the current study. Michael Lock has consulted for Sanofi Canada and has participated in a speaker's bureau for Ferring, Tersera, Esai and AbbVie, unrelated to the current study. Alexander V. Louie has received honoraria for advisory board and speaking engagements from AstraZeneca, unrelated to the current study. Shilo Lefresne has received research funding and honoraria from AstraZeneca, unrelated to the current study. Mitchell Liu has received honoraria for advisory board and speaking engagements from AstraZeneca, unrelated to the current study. Robert A. Olson has received grant funding from Varian Medical Systems, and has a consultant role with equity with Need Inc, unrelated to the current study. Benjamin Mou has received honoraria from AstraZeneca and Bristol Myers Squibb, unrelated to the current study. David A. Palma receives research funding from the Ontario Institute for Cancer Research, royalties from UptoDate.com, and has a consultant role with equity with Need Inc, unrelated to the current study. All other authors declare no conflicts of interest.