Leandro Brust

PURPOSE Epidermal growth factor receptor ( EGFR ) tyrosine kinase inhibitors (TKIs) are standard first-line therapy for EGFR -mutant, metastatic non–small cell lung cancer (NSCLC); however, most patients experience disease progression. We report results from the randomized, double-blind, phase III KEYNOTE-789 study of pemetrexed and platinum–based chemotherapy with or without pembrolizumab for TKI-resistant, EGFR -mutant, metastatic nonsquamous NSCLC (ClinicalTrials.gov identifier: NCT03515837 ). METHODS Adults with pathologically confirmed stage IV nonsquamous NSCLC, documented DEL19 or L858R EGFR mutation, and progression after EGFR-TKI treatment were randomly assigned 1:1 to 35 cycles of pembrolizumab 200 mg or placebo once every 3 weeks plus four cycles of pemetrexed and carboplatin or cisplatin once every 3 weeks and then maintenance pemetrexed. Dual primary end points were progression-free survival (PFS) and overall survival (OS). Final PFS testing was completed at the second interim analysis (IA2; data cutoff, December 3, 2021); OS was tested at final analysis (FA; data cutoff, January 17, 2023). Efficacy boundaries were one-sided P = .0117 for PFS and OS. RESULTS Four hundred ninety-two patients were randomly assigned to pembrolizumab plus chemotherapy (n = 245) or placebo plus chemotherapy (n = 247). At IA2, the median PFS was 5.6 months for pembrolizumab plus chemotherapy versus 5.5 months for placebo plus chemotherapy (hazard ratio [HR], 0.80 [95% CI, 0.65 to 0.97]; P = .0122). At FA, the median OS was 15.9 versus 14.7 months, respectively (HR, 0.84 [95% CI, 0.69 to 1.02]; P = .0362). Grade ≥3 treatment-related adverse events occurred in 43.7% of pembrolizumab plus chemotherapy recipients versus 38.6% of placebo plus chemotherapy recipients. CONCLUSION Addition of pembrolizumab to chemotherapy in patients with TKI-resistant, EGFR -mutant, metastatic nonsquamous NSCLC did not significantly prolong PFS or OS versus placebo plus chemotherapy in KEYNOTE-789.

203 Background: Anti-EGFR treatment of RAS wild-type metastatic colorectal cancer (mCRC) in Latin America includes cetuximab or panitumumab, added to chemotherapy (cet+CT and pan+CT, respectively). Adverse event (AE) profiles for each regimen may influence the treatment decision. This study aimed to estimate the associated financial impact of AE management in three countries: Argentina (AR), Brazil (BR) and Panama (PA) from a healthcare payer perspective. Methods: We revised a published Microsoft Excel-based economic model to calculate average patient- and population-level costs from a payer perspective of mCRC AE management for first-line cet+CT and pan+CT treatment, using AE frequency and severity data derived from the authorization relevant FDA prescribing information (PI), multiplied by the country-specific unit costs of managing AEs. Costs of AE management were obtained from publicly available sources in each country and converted to US dollars (USD). Country-specific market research data were applied to calculate costs at the eligible mCRC population level. The model structure and input parameters were endorsed by local practising oncologists. Results: A 17.5% (all-grade) and 31.6% (grade 3-4) lower average per patient AE frequency were estimated from the PI, for cet+CT vs pan+CT. Cost results are presented in the table. Projected AE management costs of cet+CT for the eligible mCRC population are $297,643 (AR), $124,981 (BR) and $65,895 (PA), annually, reducing current annual estimated AE costs by $42,181 (AR), $8,548 (BR) and $4,691 (PA). Conclusions: According to the average estimated AE frequencies, patients treated with cet+CT are expected to experience fewer AEs than with pan+CT. According to our analyses, the lower frequency rates could result in lower overall and severe AEs’ management costs, resulting in 12.4% (AR), 6.4% (BR) and 6.6% (PA) lower costs of AE management for cet+CT versus pan+CT.[Table: see text]