medwireNews: The addition of immunotherapy to stereotactic ablative radiotherapy (SABR) significantly improves the event-free survival (EFS) of patients with treatment-naïve, early-stage or isolated parenchymal recurrent non-small-cell lung cancer (NSCLC), indicate phase 2 results.
The risk for recurrence, disease progression, or death was reduced by a significant 62% among patients who received four cycles of nivolumab alongside SABR versus those given SABR alone, reports the research team from The University of Texas MD Anderson Cancer Center in Houston, USA.
Therefore, SABR with immunotherapy “could be a treatment option in these participants, but further confirmation from a number of currently accruing phase 3 trials is required,” comment Joe Chang and colleagues.
Writing in a commentary accompanying the research in The Lancet, Eric Brooks (University of Florida College of Medicine, Jacksonville, USA) says that the study offers “a potentially practice-changing approach.”
He adds: “Although this is only a phase 2 trial, the results are long-awaited, and finally support the much-needed use of effective and safe systemic therapy for early-stage disease.”
The I-SABR study, conducted in three hospitals in Texas, enrolled 156 patients who were medically inoperable or refused surgery for treatment-naïve stage IA–IB (tumor size ≤4 cm, N0M0), stage IIA (≤5 cm, N0M0), or stage IIB (>5 cm and ≤7 cm, N0M0) disease or had isolated parenchymal recurrences (tumor size ≤7 cm) of initially TanyNanyM0 disease.
Participants were aged a median of 72 years and the majority were women (55–70%) and White (85–94%). They were randomly allocated to receive SABR with or without four cycles of nivolumab 480 mg every 4 weeks, with the first dose administered on the same day or within 36 hours of the first SABR fraction. SABR for peripheral and central lesions that met dose–volume constraints for radiation-sensitive organs consisted of 50 Gy over four daily fractions with a simultaneous 60 Gy boost to the internal gross tumor volume. All other central lesions were treated with 70 Gy over 10 daily fractions with an 80 Gy boost to the internal gross tumor volume where feasible.
In the per-protocol population, comprising 141 patients who received the assigned therapy, the 4-year EFS rate was 77% for those treated with SABR plus nivolumab and 53% for those treated with SABR alone, a statistically significant difference equating to a hazard ratio (HR) of 0.38.
The findings were similar in the intention-to-treat population, with a significant HR of 0.42 in favor of the combined approach.
Of note, while the EFS benefit of add-on nivolumab was significant in the subgroup of patients with treatment-naïve, early-stage NSCLC, at an HR of 0.32, “there was no discernible difference” between treatments in the subgroup with isolated parenchymal recurrences, report Chang et al.
They point out, however, that the number of patients with isolated parenchymal recurrences was small and the subgroup analyses were exploratory.
In terms of safety, 10 (15%) patients in the SABR plus nivolumab group experienced adverse events of grade 3 compared with none in the SABR alone group. However, there were no grade 4 or 5 toxicities in either group.
“These findings support our hypothesis that the I-SABR strategy of combining immunotherapy with the immune-galvanising effects of SABR can reduce recurrence and increase cure rates,” write the study authors.
“As such, it might be interesting to explore the effectiveness of I-SABR compared with immunotherapy and surgery for participants with resectable, early-stage NSCLC,” they conclude.
The commentator notes that “the study is not without substantial limitations,” such as a moderate sample size, patient population heterogeneity, sparse routine PD-L1 testing for correlative analysis, and a short follow-up (median 33 months).
Nevertheless, Brooks believes that “it adds to the evidence base and offers ongoing lessons about lung cancer anti-tumour immunity.”
medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2023 Springer Healthcare Ltd, part of the Springer Nature Group
Lancet 2023; doi:10.1016/S0140-6736(23)01384-3
Lancet 2023; doi:10.1016/S0140-6736(23)01464-2