Does major pathological response after neoadjuvant Immunotherapy in resectable non-small-cell lung cancers predict prognosis? a systematic review and meta-analysis

Abstract

Objective: Overall survival is the gold-standard outcome measure for phase 3 trials, but the need for a long follow-up period can delay the translation of potentially effective treatment to clinical practice. The validity of major pathological response (MPR) as a surrogate of survival for non small cell lung cancer (NSCLC) after neoadjuvant immunotherapy remains unclear. Methods: Eligibility was resectable stage I–III NSCLC and delivery of PD-1/PD-L1/CTLA-4 inhibitors prior to resection; other forms/modalities of neoadjuvant and/or adjuvant therapies were allowed. Statistics utilized the Mantel–Haenszel fixed-effect or random-effect model depending on the heterogeneity (I 2). Results: Fifty-three trials (seven randomized, 29 prospective nonrandomized, 17 retrospective) were identified. The pooled rate of MPR was 53.8%. Compared to neoadjuvant chemotherapy, neoadjuvant chemo-immunotherapy achieved higher MPR (OR 6.19, 4.39–8.74, P<0.00001). MPR was associated with improved disease-free survival/progression-free survival/event-free survival (HR 0.28, 0.10–0.79, P=0.02) and overall survival (HR 0.80, 0.72–0.88, P<0.0001). Patients with stage III (vs I/II) and PD-L1 ≥1% (vs <1%) more likely achieved MPR (OR 1.66,1.02–2.70, P=0.04; OR 2.21,1.28–3.82, P=0.004). Conclusions: The findings of this meta-analysis suggest that neoadjuvant chemo-immunotherapy achieved higher MPR in NSCLC patients, and increased MPR might be associated with survival benefits treated with neoadjuvant immunotherapy. It appears that the MPR may serve as a surrogate endpoint of survival to evaluate neoadjuvant immunotherapy.

Clinical factors and major pathological response after neoadjuvant chemoimmunotherapy in potentially resectable lung squamous cell carcinoma

“…With the increased clinical application of NCIO for NSCLC, pCR and MPR are now internationally recognized as important predictors of treatment efficacy compared to the commonly studied endpoints of PFS and OS, which need longer follow-up times (28). Patients with pCR and MPR have better tumor prognosis and improved OS (29)(30)(31). Patients who achieved MPR were found to have increased 5-year OS from 40% to 85% (32,33).…”

Risk factors and a prognostic model for patients with borderline resectable locally advanced T3–4N0–1 non-small cell lung cancer: a population-based study

“…Neoadjuvant immunotherapy has been employed in various types of cancer ( 45 , 46 ). Since our data did not include information on immunotherapy, the potential benefits of neoadjuvant immunotherapy in T3–4N0 patients still require further discussion.…”

“…A recent meta-analysis has reported that neoadjuvant immunotherapy achieves a higher rate of major pathological response (MPR) in patients diagnosed with stage II/III NSCLC compared to neoadjuvant chemotherapy alone. Furthermore, MPR has been found to be associated with improved OS [hazard ratio (HR) 0.80, 95% CI: 0.72–0.88, P<0.001] ( 45 ). This suggests that neoadjuvant immunotherapy seems to be beneficial for patients diagnosed with both T3–4N0 and T3–4N1 NSCLC.…”

Easily applicable predictive score for MPR based on parameters before neoadjuvant chemoimmunotherapy in operable NSCLC: a single-center, ambispective, observational study

“…However, neoadjuvant chemotherapy only can increase survival rate by about 5%, and there is an urgent need for new treatment modalities to improve survival 5 . In recent years, a number of prospective clinical trials have shown that immune checkpoint inhibitors (ICIs) combined with chemotherapy produced better major pathological response (MPR) and pathological complete response (pCR) than neoadjuvant chemotherapy alone, and preliminary results have indicated that it can translate into survival benefit 6 – 10 . Therefore, the primary study endpoint of phase II and phase III clinical studies in the neoadjuvant stage is MPR or pCR 11 , 12 .…”