Stereotactic Radiation Improves Survival in Inoperable Stage I NSCLC

Patients with stage I non-small cell lung cancer (NSCLC), who are not eligible for surgical resection, can still potentially be cured with radiotherapy alone. Advances in radiotherapy technology have led to the development of stereotactic ablative body radiotherapy (SABR), a technique that enables very precise delivery of high-radiation (ablative) doses to small tumors in a short period of time (1 to 5 treatments over two weeks), with surrounding healthy tissue receiving only lower doses. Its use for the management of inoperable, peripherally-located stage I NSCLC is increasing, though there is little prospective evidence supporting the efficacy of SABR over standard radiotherapy. To evaluate the efficacy of this treatment modality, the prospective, randomized phase III CHISEL trial (N = 101), compared SABR (54Gy in three 18Gy fractions or 48Gy in four 12Gy fractions) to standard radiotherapy (66Gy in 33 daily 2Gy fractions or 50Gy in 20 daily 2.5Gy fractions) in patients with inoperable, peripherally located stage I NSCLC.

The median follow-up was 2.6 years for the SABR cohort and 2.1 years for the standard radiotherapy cohort. At data cut-off, 14% of patients receiving SABR had experienced local progression, compared to 31% of patients receiving standard radiotherapy. There was a significant improvement in freedom from local treatment failure in patients receiving SABR compared to standard radiotherapy (HR 0.32, P = .008). The 2-year rate of local control was 89% and 65% for SABR and standard radiotherapy, respectively. At data cut-off, 39% of patients in the SABR arm and 62% in the standard radiotherapy arm had died. Of note, the median overall survival (OS) was 5 years with SABR, compared to 3 years with standard radiotherapy (HR 0.53, P = .027). The 2-year OS rate was 77% with SABR and 59% with standard radiotherapy.

Treatment was generally well tolerated in both groups, though there was a slight increase in grade 3/4 adverse events (AEs) in patients receiving SABR. In the SABR group, there was 1 grade 4 AE (dyspnea) and 7 grade 3 AEs (2 cough, 1 hypoxia, 1 lung infection, 1 weight loss, 1 dyspnea, 1 fatigue). In the standard radiotherapy group, there were 2 grade 3 AEs (chest pain) and no grade 4 AEs. However, quality of life was not significantly different between the groups.

The investigators concluded that, compared to standard radiotherapy, SABR results in a significant improvement in local disease control and survival in patients with peripherally located inoperable stage I NSCLC and should be the treatment of choice for these patients. In an accompanying commentary, the authors agreed that SABR should be considered a standard of care for patients with inoperable stage I NSCLC, and further added that the impressive OS benefit seen with SABR in this trial suggest a potential role for this treatment in operable patients as an alternative to surgery. Additionally, the potential for SABR in combination with immunotherapy is something that should be investigated in clinical trials, given the synergistic activities of these two treatment modalities.

Lancet Oncol. 2019 Feb 12. [Epub ahead of print].

Clinical Opinion Poll

When would you recommend dabrafenib + trametinib combo for a patient with advanced, symptomatic, PD-L1–low, lung adenocarcinoma and BRAF V600 mutation?