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25-06-2021 | Non-small-cell lung cancer | News

Adding SBRT to neoadjuvant durvalumab shows promise in early NSCLC

Hannah Kitt

medwireNews: The addition of stereotactic body radiotherapy (SBRT) to neoadjuvant durvalumab significantly improves the major pathologic response (MPR) rate in patients with early-stage non-small-cell lung cancer (NSCLC), phase 2 trial data suggest.

“In contrast to prevailing strategies, combining immunotherapy with stereotactic body radiotherapy might be associated with a more favourable safety profile and higher patient compliance than is currently reported using combinations with full-dose chemotherapy or chemoradiation,” say Nasser Altorki (Weill Cornell Medicine–New York Presbyterian Hospital, USA) and colleagues.

The open-label trial included 60 patients with stage I–IIIA tumors who were randomly assigned to either receive SBRT in three daily fractions of 8 Gy followed by two cycles of neoadjuvant durvalumab 1.12 g given 3 weeks apart or the PD-L1 inhibitor alone.

Altorki et al say in The Lancet Oncology: “This dose and fractionation were selected based on preclinical evidence for the immunogenicity of this type of regimen, and because of concerns about safety due to overlapping organ toxicities of lung stereotactic body radiotherapy and durvalumab, particularly when used preoperatively in patients with operable NSCLC.”

MPR, defined as having 10% or fewer viable tumor cells in the primary tumor, was achieved by 53.3% of patients who received SBRT plus durvalumab and 6.7% of those given durvalumab alone, a significant difference that equated to a 16-fold increased probability of MPR with the addition of SBRT.

Of note, half of the responses in the SBRT group were complete – defined as the absence of viable tumor cells in the tumor and lymph node specimens – while there were no complete responses in the control group.

No patient in either group had a complete radiographic response, but partial radiographic responses occurred in 46.7% of patients treated with SBRT plus durvalumab and 3.3% of those given durvalumab alone.

The study authors highlight “the significant imbalance in PD-L1 expression between groups,” but note that a post-hoc multivariable analysis adjusted for baseline PD-L1 expression still showed a significant 12.6 times increased likelihood of MPR with the addition of SBRT to immunotherapy.

An identical 87% of patients in the SBRT and control groups underwent surgical resection as planned – at a median of 5.3 and 5.4 weeks, respectively, from the initiation of durvalumab – and the resection was complete in a respective 96% and 88%.

The researchers note that the median time to resection was “considerably shorter than the 12–16 weeks commonly required for preoperative therapy using chemotherapy or chemoradiotherapy, without higher toxicity or any apparent reduction in activity, as measured by major pathological response.”

Grade 3–4 adverse events (AEs) were reported in 20% of patients given the combination and 17% of those given durvalumab alone, most commonly hyperlipasemia (10 vs 0%) and hyperglycemia (7 vs 0%). Three patients in the SBRT–durvalumab group did not receive the second cycle of durvalumab due to grade 2 pancreatitis, grade 3 hepatitis, and grade 3 fatigue and thrombocytopenia, respectively.

Serious AEs occurred in two patients in each group, but there were no treatment-related deaths or deaths within 30 days of surgery.

The team cautions that “neither major pathological response nor complete pathological response are validated survival surrogates in patients with lung cancer,” but nevertheless concludes that “the robust and better than expected effect size between the groups in major pathological response is promising and merits confirmation in a larger trial.”

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2021 Springer Healthcare Ltd, part of the Springer Nature Group

Lancet Oncol 2021; doi:10.1016/S1470-2045(21)00149-2

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