Temozolomide Alone or Combined with Capecitabine in Metastatic Neuroendocrine Neoplasia

2020 Year in Review - Neuroendocrine Tumors —January 9, 2021

Results of a retrospective real-world data analysis indicate that temozolomide-based regimens are associated with a high disease control rate (DCR) and a manageable toxicity profile in patients with metastatic neuroendocrine neoplasms (NENs).

To better characterize the outcomes of temozolomide-based chemotherapy in metastatic neuroendocrine neoplasia, the use of temozolomide alone and in combination with capecitabine was retrospectively analyzed using clinical data from a real-world setting. The data were presented at the European Society for Medical Oncology Virtual Congress 2020.

The study cohort included a total of 100 consecutive patients with metastatic NENs who were treated with temozolomide monotherapy or temozolomide + capecitabine between 2009 and 2019 at Osteoncology and Rare Tumors Center, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori IRCCS. The treatment regimen consisted of temozolomide 150 mg/m2 on days 1 to 5 every 28 days for the first cycle, increased to 200 mg/m2 on days 1 to 5 every 28 days, or capecitabine 750 mg/m2 twice daily on days 1 to 14 plus temozolomide 200 mg/m2 daily on days 10 to 14 every 28 days. Ondansetron prophylaxis was administered 30 minutes before temozolomide. Pretreatment tumor growth rate (TGR0), overall survival (OS), progression-free survival (PFS), tolerance, objective response rate (ORR), and DCR were calculated.

Overall, 95 patients received temozolomide-based therapy, with 70 patients treated with temozolomide monotherapy and 25 patients treated with the temozolomide + capecitabine regimen. The majority of patients were male (57.9%); the median age was 59 years (range, 26-85 years). The primary tumor sites were predominantly in the lung (28.7%), pancreas (26.5%), and gastrointestinal tract (33.3%). The majority of tumors were well-differentiated (72.6%), and were classified as neuroendocrine tumor (NET) grade 1 (13.7%) and grade 2 (55.8%).

In the total population, the median PFS was 10.4 months (95% confidence interval [CI], 6.0-11.5) and median OS was 23.4 months (95% CI, 17.0-29.0). In patients evaluable for response (N = 86), the ORR was 44.1%, with a DCR of 70.9%. Between-group comparisons showed median PFS (10.7 vs 9.3 months; P = .405) and median OS (23.9 vs 20.5 months; P = .585) to be similar for the temozolomide monotherapy and temozolomide + capecitabine treatment groups.

In multivariate analysis, the risk for progression was found to be higher for patients with grade 3 neuroendocrine carcinoma (NEC; hazard ratio [HR], 2.70; 95% CI, 1.25-5.84) and TGR0 ≥19.55 cohort (HR, 2.53; 95% CI, 1.45-4.40). A higher risk for death was also associated with the TGR0 ≥19.55 cohort (HR, 2.18; 95% CI, 1.16-4.11) compared with those with TGR0 <19.55; similarly, the NEC grade 3 cohort also showed a higher risk for death (HR, 2.42; 95% CI, 1.04-5.59) compared with the NET grade 1/2/3 cohorts. No differences by primary tumor site were noted.

The adverse event (AE) profile was predominantly grade 1/2 in severity. The most common AEs included anemia, neutropenia, and headache; grade 3 neutropenia and thrombocytopenia were rarely reported.

These results indicate that temozolomide-based regimens are associated with a high DCR and a manageable toxicity profile in patients with metastatic NENs, with clinical benefit extending to patients with NET grade 3 tumors.

Source: Bongiovanni A, et al. Ann Oncol. 2020;31(4_suppl). Abstract 1175P.

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Last modified: January 11, 2021

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