31P Myelosuppression risk from epidermal growth factor receptor-tyrosine kinase inhibitors, carboplatin chemotherapy, or both in EGFR mutated non-small cell lung cancer (NSCLC)

The addition of carboplatin-doublet chemotherapy (CBCT) to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) improves progression-free survival in EGFR mutated NSCLC. However, both classes of agents are associated with myelosuppression presenting as neutropenia, anemia, and/or thrombocytopenia. We evaluated rates of myelosuppression (any grade) for EGFR-TKIs alone and in combination with CBCT. A systematic literature review (SLR) was conducted to summarize the incidence of myelosuppression events reported in clinical trials evaluating EGFR-TKIs alone, CBCT alone, or both among patients with EGFR-mutant advanced NSCLC. Searches were conducted in Embase and MEDLINE to identify full-text articles and conference proceedings published between 2010 and 2023 that met prespecified inclusion criteria. Sixteen trials, including 14 randomized controlled trials, were included. Twelve trials evaluated first-line treatments, and 4 evaluated second-line or later. Included trials assessed 1st- and 3rd-generation TKIs; none assessed 2nd generation TKIs. Across trials, the weighted average incidence of any-grade myelosuppressive events for 1st generation TKIs plus CBCT versus CBCT alone was 63.4% vs 44.7% for anemia, 61.8% vs 38.9% for neutropenia, and 48.2% vs 35.1% for thrombocytopenia. The incidence for any-grade myelosuppressive events for 3rd generation TKIs plus CBCT versus CBCT alone was 71.7% vs 44.7% for anemia, 88.7% vs 38.9% for neutropenia, and 73.6% vs 35.1% for thrombocytopenia.Table: 31PAnemiaNeutropeniaThrombocytopeniaTreatmentNo. of studiesRange, %Mean, % (n/N)Range, %Mean, % (n/N)Range, %Mean, % (n/N)1G TKI24.8–21.115.7 (40/254)4.1–6.04.7 (12/254)5.3–3.64.7 (12/254)3G TKI17.57.5 (21/279)7.97.9 (22/279)10.010.0 (28/279)CBCT230.1–72.244.7 (93/208)22.8–69.438.9 (81/208)19.9–63.935.1 (73/208)1G TKI + CBCT238.1–66.563.4 (121/191)59.4–81.061.8 (118/191)4.8–53.548.2 (92/191)3G TKI + CBCT230.0–97.071.7 (38/53)87.9–90.088.7 (47/53)40.0–93.973.6 (39/53)Means calculated as total events/total participants across trials. Most studies did not evaluate cytopenic events in the first 14 days of treatment when the rate of cytopenia is highest. Open table in a new tab Means calculated as total events/total participants across trials. Most studies did not evaluate cytopenic events in the first 14 days of treatment when the rate of cytopenia is highest. Adding EGFR TKIs to CBCT results in higher rates of cytopenic events than seen with CBCT or TKI monotherapy alone. Risk was higher for 3rd generation TKIs, especially for neutropenia and thrombocytopenia.