Abstract 31P
Background
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.
Methods
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.
Results
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: 31P
| Anemia | Neutropenia | Thrombocytopenia | ||||||
| Treatment | No. of studies | Range, % | Mean, % (n/N) | Range, % | Mean, % (n/N) | Range, % | Mean, % (n/N) | |
| 1G TKI | 2 | 4.8–21.1 | 15.7 (40/254) | 4.1–6.0 | 4.7 (12/254) | 5.3–3.6 | 4.7 (12/254) | |
| 3G TKI | 1 | 7.5 | 7.5 (21/279) | 7.9 | 7.9 (22/279) | 10.0 | 10.0 (28/279) | |
| CBCT | 2 | 30.1–72.2 | 44.7 (93/208) | 22.8–69.4 | 38.9 (81/208) | 19.9–63.9 | 35.1 (73/208) | |
| 1G TKI + CBCT | 2 | 38.1–66.5 | 63.4 (121/191) | 59.4–81.0 | 61.8 (118/191) | 4.8–53.5 | 48.2 (92/191) | |
| 3G TKI + CBCT | 2 | 30.0–97.0 | 71.7 (38/53) | 87.9–90.0 | 88.7 (47/53) | 40.0–93.9 | 73.6 (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.
Conclusions
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.
Editorial acknowledgement
Medical writing assistance was provided by Evidera and Lumanity Communications Inc and funded by Janssen Global Services LLC.
Legal entity responsible for the study
Janssen Pharmaceuticals.
Funding
Janssen Pharmaceuticals.
Disclosure
N. Girard: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, MSD, Roche, Pfizer, Mirati, Amgen, Novartis, Sanofi, Gilead; Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, MSD, Roche, Pfizer, Janssen, Boehringer, Novartis, Sanofi, AbbVie, Amgen, Lilly, Grunenthal, Takeda, Owkin, Leo Pharma, Daiichi Sankyo, Ipsen; Financial Interests, Institutional, Research Grant, Local: Roche, Sivan, Janssen; Financial Interests, Institutional, Funding: BMS, Leo Pharma; Financial Interests, Institutional, Research Grant: MSD; Other, Personal, Other, Family member is an employee: AstraZeneca. S.V. Liu: Financial Interests, Personal, Advisory Board, Consultant: AstraZeneca, Elevation Oncology, Genentech / Roche, Janssen, Jazz Pharmaceuticals, Novartis, Regeneron, Sanofi, Turning Point Therapeutics; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Catalyst, Eisai, Gilead, Guardant Health, Merus, Takeda; Financial Interests, Personal, Other, Consultant: Daiichi Sankyo, Merck; Financial Interests, Institutional, Invited Speaker: Alkermes, Elevation Oncology, Gilead, Merck, Merus, Nuvalent, RAPT, Turning Point Therapeutics; Financial Interests, Institutional, Invited Speaker, Local PI: Genentech; Non-Financial Interests, Personal, Member: ASCO, IASLC. W. Nassib William Junior: Financial Interests, Personal, Invited Speaker: Amgen, Genentech / Roche, Eli Lilly, BMS, Pfizer, Janssen, United Medical; Financial Interests, Personal, Advisory Board: AstraZeneca, Merck, Bayer, Sanofi, Takeda, Novartis; Financial Interests, Personal, Expert Testimony: Boehringer Ingelheim. K. Schaible: Financial Interests, Personal, Full or part-time Employment: Evidera. D. Junqueira: Financial Interests, Personal, Full or part-time Employment: Evidera. H. Burnett: Financial Interests, Personal, Full or part-time Employment: Evidera. P. Mahadevia: Financial Interests, Personal, Full or part-time Employment: Janssen; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. M. Chioda: Financial Interests, Personal, Full or part-time Employment: Janssen; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. J.M. Bauml: Financial Interests, Personal, Full or part-time Employment: Janssen; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. N. Leighl: Financial Interests, Personal, Other, CME/independent lectures: MSD, BMS, Hoffmann LaRoche, EMD Serono; Financial Interests, Personal, Invited Speaker, independent lectures: Novartis, Takeda; Financial Interests, Personal, Advisory Board: Puma Biotechnology; Financial Interests, Institutional, Research Grant: Amgen, AstraZeneca, Array, Bayer, EMD Serono, Guardant Health, Lilly, MSD, Pfizer, Roche, Takeda, Janssen.