Introduction: Literature suggests an increased risk of mortality in patients with solid tumors and thrombocytopenia, but data on OS after pCIT are limited, particularly in patients with mCRC receiving chemotherapies known to cause thrombocytopenia. A more detailed description of patients who develop pCIT and factors associated with OS will help assessment of the clinical burden and potential supportive therapy.

Methods: From the Flatiron-Health Enhanced Data Mart, patients diagnosed with mCRC between January 1, 2011 to March 31, 2023 were included. pCIT was defined as the first occurrence of a platelet count measurement ≤85×109/L, ≥13 days after the nearest prior chemotherapy administration with fluorouracil and oxaliplatin (FOLFOX) or fluorouracil, irinotecan, and oxaliplatin (FOLFOXIRI); or ≥ 20 days after oxaliplatin and capecitabine (CAPOX). Inclusion of other concurrent antineoplastic agents was allowed. The time from the first pCIT to death was summarized using the Kaplan-Meier estimator, stratified by line of therapy (LOT), age, sex, race, Eastern Cooperative Oncology Group (ECOG), CIT grade at the first pCIT onset, and use of epidermal growth factor receptor (EGFR) inhibitors and bevacizumab.

Results: A total of 2,367 patients with mCRC had their first pCIT following FOLFOX (87.8%), FOLFOXIRI (5.6%), and CAPOX (6.6%). The median time from the first date of index LOT to the first pCIT was 89 days (IQR 49, 135). Most patients had their first pCIT in the first LOT (77.5%), while 14.6%, 4.4% and 3.5% had one in the second, third, and fourth or more LOT, respectively. Forty-seven percent were ≥65 years; 59% were male; 68% were White. Eighty-eight percent were from community oncology practices. Thirty-one percent, 35.3%, and 8.0% of patients had ECOG score of 0, 1, and ≥2, respectively. Prior or current use of EGFR inhibitors and bevacizumab were identified in 10.5% and 58.9% of patients, respectively. Most patients had CIT Grade 1 (75 to ≤85×109/L; 58.6%) or Grade 2 (50 to <75×109/L; 36.4%) at the first pCIT onset, while 5.0% had Grade 3 (25 to <50x109/L) or Grade 4 (<25x109/L).

From the time of first pCIT in the first LOT, the median OS was 23.5 months (95% CI 21.8-24.4), with 6, 12, and 24-month survival probabilities of 0.90 (95% CI 0.89-0.92), 0.74 (95% CI 0.72-0.76), and 0.49 (95% CI 0.46-0.51), respectively. The median OS was 26.9 months (95% CI 24.4-29.9) in patients <65 years; 20.6 months (95% CI 19.2-21.8) in patients ≥65 years; 21.8 months (95% CI 20.5-23.6) in males; 26.0 months (95% CI 23.4-29.7) in females; 23.3 months (95% CI 21.7-24.7) in White patients; 23.6 months (95% CI 14.8-35.6) in Asian patients; 23.9 months (95% CI 18.4-27.9) in Black or African American patients. The median OS was 30.3 months (95% CI 25.7-33.9), 20.7 months (95% CI 19.2-22.9), and 15.5 months (95% CI 11.2-18.4) in ECOG 0, 1, and ≥2, respectively. The median OS was 24.2 months (95% CI 22.6-26.7), 23.0 months (95% CI 20.5—24.7), 19.8 months (95% CI 17.2-51.5), and 10.8 months (95% CI 7.6-16.1) in CIT Grade 1, 2, 3, and 4, respectively. The median OS was 30.3 months (95% CI 20.2-36.5) in those with current or prior EGFR inhibitor; 23.3 months (95% CI 21.8-24.3) in those without EGFR inhibitors; 21.0 months (95% CI 19.5-22.3) in those with current or prior bevacizumab; and 28.3 months (95% CI 24.6-30.8) in those without bevacizumab.

From the time of first pCIT in the second, third, and fourth or more LOT, the median survival was 15.9 months (95% CI 14.5-19.4), 9.7 months (95% CI 6.9-11.2), and 11.2 months (95% CI 8.0-12.4), respectively. The 6-month survival probabilities in the same groups were 0.84 (95% CI 0.80-0.87), 0.64 (0.54-0.73), and 0.71 (0.60-0.80).

Conclusion: The median OS for mCRC patients following the first pCIT ranges from 9.7 to 23.5 months, with 6-month survival probabilities between 64% and 90%, across different LOTs. Multiple factors, such as LOT, ECOG, age, CIT grade, and bevacizumab use, are associated with clinically relevant differences in survival in patients with pCIT. These findings provide clinically relevant benchmarks for survival and may be useful in assessing the need for supportive therapy. Direct comparisons with other mCRC OS or CIT studies should be approached cautiously, as this study followed up patients from the first pCIT, and their characteristics may differ, such as history of pCIT, LOT, disease severity, and cancer treatment patterns, which can affect mortality outcome.

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2025
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