Temozolomide in Advanced Leiomyosarcoma, Immunotherapy Sensitization

Background

Retrospective cohort, N=47 anthracycline+temozolomide (TEM), N=18 gemcitabine+TEM in advanced leiomyosarcoma (LMS); subset (n=6) received subsequent PD-1 inhibitor after TEM-based therapy.

Interventions and follow up

Arm A: Anthracycline + temozolomide
Arm B: Gemcitabine + temozolomide
Primary endpoint: Overall survival, progression-free survival
mFollow up: Median OS 31.0 months (all TEM-treated); median PFS 10.0 month

Results

Subset: Post-TEM PD-1 immunotherapy rechallenge (n=6)
Overall population: mOS 31.0 months, mPFS 10.0 months
Immunotherapy post-TEM subgroup (n=6): mOS 45.0 months, mPFS 13.0 months (vs 23.5 months OS, 5 months PFS without immunotherapy)
MGMT negativity: Trend toward improved OS

Adverse events

Main adverse events: TEM-related toxicities standard (myelosuppression expected); grade 3+ rates and specific incidences not detailed in abstract; manageable with supportive care.

Conclusions

TEM-based regimens effective in advanced LMS. Post-TEM biopsies revealed dynamic changes in mismatch repair gene expression, tertiary lymphoid structures, and combined positive score, suggesting tumor microenvironment remodeling that may prime for immunotherapy sensitivity.

Key Limitations

Key Limitations: Small subset for immunotherapy (n=6); retrospective design; no control arm without TEM; single-center; heterogeneous prior therapies not fully characterized; PD-1 inhibitor selection not specified.

Clinical Context

LMS historically resistant to checkpoint inhibitors; this data suggests sequential TEM→immunotherapy may overcome resistance via microenvironment priming. Warrants prospective evaluation and may inform future LMS treatment sequencing algorithms.

References

References: Tan et al, Anticancer Drugs 2026