Comparison of different maintenance regimens following first-line immunochemotherapy for advanced non-small cell lung...

Immunochemotherapy is the standard first-line treatment for non-small cell lung cancer (NSCLC). However, the ideal combination strategy and maintenance regimen remain uncertain. This study aims to compare the clinical efficacy of different first-line maintenance regimens for advanced EGFR/ALK (epidermal growth factor receptor/anaplastic lymphoma Kinase) negative NSCLC and explore the eligibility of chemo-free maintenance.

We conducted a retrospective evaluation of 1,510 EGFR/ALK negative NSCLC patients who received immune checkpoint inhibitors (ICIs) treatment in our center from 2019 to 2021. Patients who had controlled disease after 2-6 cycles of first-line ICIs in combination with platinum-based doublet chemotherapy with or without anti-angiogenesis were included. Four maintenance regimens were analyzed: ICIs plus platinum-free chemotherapy with (group 1, I+C+A) or without anti-angiogenesis maintenance (group 2, I+C), single-agent ICIs maintenance (group 3, I) or ICIs plus anti-angiogenesis maintenance (group 4, I+A). For group 3-4, rechallenge with initial chemo-agents was given upon the first progression, those who achieved controlled disease were repeatedly followed by another chemo-free period. The primary outcome was progression-free survival (PFS). Notably, for group 3-4, PFS was characterized as the duration between treatment initiation and failure of rechallenge (last disease progression).

In total, 140 eligible patients in the maintenance phase were analyzed, with 20, 40, 42, and 38 patients in groups 1 to 4, respectively, displaying comparable baselines. Median PFS was similar in the I+C+A maintenance group (22.6 months), I+C maintenance group (21.0 months), and I+A maintenance group (21.5 months), whereas PFS was inferior in group 4 with I maintenance alone (13.4 months). Median chemo-free duration were 6.3 months in I maintenance group, while 13.5 months in I+A maintenance group. During the maintenance period of group 1 to 4, 25%, 25%, 19%, and 42% of patients experienced partial response (PR) again, respectively. Fifty-five percent, 65%, 48% and 61% of patients sustained durable disease control at the end of follow-up. In group 4, 39% of patients received progressive disease (PD) and rechallenge initial chemo-agents. Fifty percent of patients achieved PR and resumed to chemo-free maintenance.

We showed that following first-line immunochemotherapy, chemo-free maintenance by ICIs plus anti-angiogenesis and on-demand chemo-rechallenge provided comparable efficacy to chemo-on maintenance in terms of PFS, thus allowing the minimization of cytotoxic drugs without compromising therapeutic effectiveness. In addition, anti-angiogenesis is essential during chemo-free maintenance.