Consolidation nivolumab and ipilimumab or nivolumab alone following concurrent chemoradiation for patients with NSCLC
Following concurrent chemoradiation for unresectable stage III non-small cell lung cancer, both nivolumab alone and nivolumab and ipilimumab combined demonstrated improved 18- month progression-free survival compared with historical controls despite a shortened interval (6 months) of treatment. The research was presented today at the IASLC 2022 World Conference on Lung Cancer in Vienna.
The PACIFIC trial demonstrated that a year of consolidation PD-(L)1 inhibition following concurrent chemoradiation (CRT) for unresectable stage III NSCLC improves overall survival, but the optimal duration of consolidation immunotherapy in this setting is undefined.
Studies in metastatic NSCLC demonstrate that combination PD-(L)1/CTLA-4 inhibition improves overall survival compared to chemotherapy alone. This trial evaluated the use of combination nivolumab plus ipilimumab or nivolumab alone for up to six months in unresectable stage III NSCLC after concurrent chemoradiation.
Dr. Greg Durm, Indiana University Melvin and Bren Simon Cancer Center, Bloomington, Ind., and colleagues created a randomized phase II, multicenter trial of 105 patients with unresectable stage IIIA/IIIB NSCLC. All patients received concurrent chemoradiation and were then enrolled and randomized 1:1 to receive nivolumab 480mg IV q4wks (Arm A) for up to 24 weeks or nivolumab 3mg/kg IV q2 weeks and ipilimumab 1mg/kg IV q6 weeks (Arm B) for up to 24 weeks. The primary endpoint is 18-month progression-free survival compared to historical controls of chemoradiation alone for arm A (30%) and chemoradiation followed by durvlumab for arm B (44%).
From September 2017 to April 2021, 105 pts were enrolled and randomized, 54 to N alone (A) and 51 to N + IPI (B). The baseline characteristics for arm A/B: median age (65/63), male (44.4%/56.9%), stage IIIA (55.6%/56.9%), stage IIIB (44.4%/43.1%), non-squamous (57.4%/54.9%), and squamous (42.6%/45.1%). The percentage of pts completing the full treatment was 70.4% in A and 56.9% in B (p=0.15). Median f/u was 24.5 and 24.1 months on A and B, respectively.
The 18- month progression-free survival was 62.3% on Arm A (p <0.1) and 67% on Arm B (p <0.1), and median progression-free survival was 25.8 months and 25.4 months, respectively. Median overall survival was not reached on either arm, but the 18- and 24-month overall survival estimates were 82.1% and 76.6% for Arm A and 85.5% and 82.8% for Arm B, respectively.
Treatment-related adverse events (trAE) on Arm A were 72.2% and 80.4% on Arm B and grade ≥3 trAEs on arm A/B were 38.9%/52.9%. There was one grade five event in each arm (COVID19-in Arm A, cardiac arrest in Arm B). The number of patients with grade ≥2 pneumonitis was 12 (22.2%) in Arm A and 15 (29.4%) in Arm B, with 5 (9.3%) and 8 (15.7%) grade ≥3 events, respectively. The most common (>10%) non-pneumonitis trAEs in A were fatigue (31.5%), rash (16.7%), dyspnea (14.8%), and hypothyroidism (13%), and in B were fatigue (31.4%), diarrhea (19.6%), dyspnea (19.6%), pruritus (17.7%), hypothyroidism (15.7%), rash (15.7%), arthralgia (11.8%), and nausea (11.8%).
Following concurrent CRT for unresectable stage III NSCLC, both N and N + IPI demonstrated improved 18- month PFS compared with historical controls despite a shortened interval (6 months) of treatment. OS data are still maturing but 18- and 24-month OS estimates compare favorably to prior consolidation trials. Toxicity for N alone was similar to prior single-agent trials, and the combination of N + IPI resulted in a higher incidence of trAE's, although consistent with prior reports.
