Pereira, Rafael Alvim

373 Background: Recent studies have demonstrated encouraging outcomes with neoadjuvant ICIs in pts with localized deficient mismatch repair (dMMR) and/or microsatellite instability-high (MSI-H) GEC, prompting discussions around the feasibility of nonoperative management (NOM). However, current evidence is largely from phase 1 and 2 clinical trials with limited sample sizes. Thus, the efficacy and safety of neoadjuvant ICI in this pt population remain subject to ongoing debate. Methods: We conducted a systematic review and meta-analysis of prospective and retrospective studies evaluating neoadjuvant ICIs in pts with localized dMMR/MSI-H GEC according to the PRISMA guidelines. The primary outcomes were pathological complete response (pCR) and complete clinical response (cCR) rates. cCR was defined as no evidence of residual disease on tumor-specific imaging and on endoscopy with biopsy. Secondary outcomes included major pathologic response (MPR) rates and the incidence of grade 3–4 immune-related adverse events (irAEs). Proportions with 95% confidence intervals (CI) were used to pool event rates for occurrence of cCR, pCR, MPR and grade 3-4 irAEs. The DerSimonian and Laird random-effects model was used. NOM was assessed as part of the qualitative analysis. Results: 20 studies comprising 396 pts treated with neoadjuvant ICIs were included. Three studies utilized double ICI blockade (PD-1/ PD-L1 inhibitor plus CTLA-4 inhibitor), while the remaining studies primarily utilized monotherapy with a PD-1 inhibitor, with or without chemotherapy. Overall, 320 (81.0%) underwent surgical resection. The pooled pCR rate was 41.6% (95% CI, 33.1%–50.8%), cCR 63.8% (95% CI, 45.6%–78.8%), and MPR 64.2% (95% CI, 49.1%–76.9%). The pooled incidence of grade 3–4 irAEs was 5.1% (95% CI, 0.6%–12.2%). Subgroup analysis showed higher pCR with ≥3 months versus <3 months of ICI (50.2% [95% CI 42.2–58.3] vs 28.4% [18.9–40.2]; χ²=8.69, p=0.003). Forty-four pts were managed with NOM, two experienced early local regrowth over median follow-up ranging from 11.5 to 28 months. Conclusions: Neoadjuvant ICI therapy appears to be a safe and effective therapeutic strategy for pts with localized dMMR/MSI-H GEC. Neoadjuvant ICI exposure for ≥3 months seems to yield higher pCR rates than <3 months. The high and prolonged cCR rates support the nonoperative strategy in selected patients with dMMR/MSI-H GEC.

PURPOSE Lung cancer remains a leading cause of cancer mortality in Brazil, with non–small cell lung cancer (NSCLC) accounting for 85% of cases, with 1.6% carrying epidermal growth factor receptor (EGFR) exon 20 mutations. In the phase I CHRYSALIS trial (ClinicalTrials.gov identifier: NCT02609776 ), amivantamab demonstrated a median overall survival (OS) of 22.8 months versus 8.3 months with docetaxel, the standard second-line Brazil's Unified Health System (SUS) therapy. Although the Brazilian Health Regulatory Agency approved amivantamab, the National Commission for the Incorporation of Technologies’ cost-effectiveness reviews result in an average 10-year delay before SUS incorporation. We aimed to estimate premature deaths and life-years lost attributable to this access gap. METHODS Using National Institute of Cancer (INCA) data, we estimated SUS-eligible patients, NSCLC prevalence, and EGFR exon 20 frequency. Stage distribution and 5-year recurrence rates identify candidates for amivantamab. A hazard ratio (HR) was derived from the inverse exponential method (ln(2)/OS ratio). Preventable deaths were calculated as: eligible patients × (1 – HR). Life-years gained per patient were estimated as OS difference. RESULTS Of the 26,548 new patients with lung cancer, 18,973 are SUS-eligible, 16,127 have NSCLC, and 258 have EGFR exon 20 mutations. Metastatic disease accounts for 114, whereas recurrences occur in 60 (stage III), eight (II), and four (I), totaling 186 candidates annually. With an HR of 0.364, the annual preventable death in the base-case scenario is equal to 186 × (1 – 0.364) × 95% = 112 patients. Over 10 years, 1,120 premature deaths and 1,353 life-years could be avoided. CONCLUSION Delayed SUS incorporation of amivantamab may result in over a 1,000 preventable deaths and life-years lost among Brazilian EGFR exon 20–mutated NSCLC. Urgent real-world studies and cost-effectiveness analyses are needed.