Top Line: Regional and/or distant recurrences remain the biggest oncologic downside to exceedingly well-tolerated ablative radiation for early stage non-small cell lung cancer (NSCLC).
The Study: A randomized phase 2 study is finally here to begin to answer the question we’ve all been wondering for a while now: can the addition of immune checkpoint inhibition help across a broad population receiving ablative radiation for radiographic early-stage disease? It randomized 141 patients with biopsy-confirmed T1-2N0 non-small cell lung cancer receiving definitive ablative radiation to +/- the addition of nivolumab q4 weeks x 4 to start on day 1 of radiation. Importantly, median tumor size was <2 cm and only 12% of patients had tumors over 3 cm so these are really early-stage folks here. However, they did allow recurrent tumors (n=28, 20%). Radiation was delivered to 50 Gy in 4 fractions when safe (87%) and 70 Gy in 10 fractions in no-fly zone (13%). And…dun dun dun…at a median follow-up of 33 months, the primary endpoint of event-free survival was significantly increased from 53 → 77% with the addition of nivo, producing an impressive hazard ratio of 0.38. The benefit was more pronounced among the minority of patients with known PD-L1 >1% but persisted regardless. And recurrence was reduced at all sites: local from 13 → 0%, regional 11 → 6%, and distant 16 → 3%. There did not appear to be any increase in the very low rates of radiation toxicity with the addition of nivo.
TBL: In this randomized phase 2 trial, the addition of just 4 cycles of nivolumab significantly improved event free survival. Larger phase 3 studies may usher in immune checkpoint inhibition as part of the package with the non-operative management of early stage NSCLC. | Chang, Lancet 2023
The Study: A randomized phase 2 study is finally here to begin to answer the question we’ve all been wondering for a while now: can the addition of immune checkpoint inhibition help across a broad population receiving ablative radiation for radiographic early-stage disease? It randomized 141 patients with biopsy-confirmed T1-2N0 non-small cell lung cancer receiving definitive ablative radiation to +/- the addition of nivolumab q4 weeks x 4 to start on day 1 of radiation. Importantly, median tumor size was <2 cm and only 12% of patients had tumors over 3 cm so these are really early-stage folks here. However, they did allow recurrent tumors (n=28, 20%). Radiation was delivered to 50 Gy in 4 fractions when safe (87%) and 70 Gy in 10 fractions in no-fly zone (13%). And…dun dun dun…at a median follow-up of 33 months, the primary endpoint of event-free survival was significantly increased from 53 → 77% with the addition of nivo, producing an impressive hazard ratio of 0.38. The benefit was more pronounced among the minority of patients with known PD-L1 >1% but persisted regardless. And recurrence was reduced at all sites: local from 13 → 0%, regional 11 → 6%, and distant 16 → 3%. There did not appear to be any increase in the very low rates of radiation toxicity with the addition of nivo.
TBL: In this randomized phase 2 trial, the addition of just 4 cycles of nivolumab significantly improved event free survival. Larger phase 3 studies may usher in immune checkpoint inhibition as part of the package with the non-operative management of early stage NSCLC. | Chang, Lancet 2023