TTFields therapy shows great potential for versatile clinical application across solid tumors1-3
As a highly versatile first-in-class modality, TTFields therapy has significant potential for broad applicability across solid tumor types and lines of therapy1-3
Investigation of TTFields therapy across tumor types
- Investigation of TTFields therapy is ongoing across clinical trials in multiple tumor types4-10
- The anticancer effects of TTFields therapy have been studied across > 10 tumor types in vitro4-10
TTFields therapy may be safely used with other cancer treatments
- In 2 approved indications, TTFields therapy was well-tolerated, suggesting a potential of low risk of additive systemic toxicity when used with other cancer treatment modalities.2,11
Preclinical evidence in cancer cells shows enhanced effects when TTFields is used concomitantly with other modalities4-10
Due to its multimechanistic actions, TTFields therapy can be added to cancer treatment modalities in approved indications and has demonstrated enhanced effects across solid tumor types when used with chemotherapy, radiation therapy (RT), immune checkpoint inhibitors (eg, PD-1/L1), or PARP inhibition in preclinical models.
Dive deeper into the enhanced effects of TTFields when used with other cancer modalities
Select any of the 4 modalities to explore its concomitant effects with TTFields.
With chemotherapy
TTFields used with a chemotherapeutic microtubule stabilizing agent (paclitaxel) has demonstrated enhanced effects, including synergy, in multiple preclinical tumor models.1,12,13
Cellular LDH was evaluated at the end of treatment and was used as a surrogate for cell count.1,12,13
With radiation therapy (RT)
TTFields used with RT, a therapy that induces DNA damage, have demonstrated enhanced effects in preclinical models, particularly when TTFields preceded RT.1,12,14-19
Decreased viability of malignant U-118 MG cells followed concomitant application of TTFields and varying doses of ionizing radiation.19
With DNA damage repair inhibitors
- Preclinical evidence has indicated TTFields' ability to disrupt DNA damage repair (including induction of double-strand breaks) when used with existing treatments designed for that effect19
- TTFields used with a PARP inhibitor that inhibits DNA damage repair (olaparib) have demonstrated a synergistically enhanced cytotoxic effect in preclinical cell lines (ie, the decrease in clonogenic survival of H157 and H1299 cells)14,16
Immuno-oncology (IO) agents
Preclinical evidence suggests that combining TTFields with IO agents designed to stimulate an immune response has the potential for enhanced effects:
- TTFields used with PD-1 inhibition have demonstrated decreased tumor size, increased immune cell infiltration, and increased cytokine production (eg, IFN-γ) versus monotherapy alone as assessed in tumor models20
Tumor volume (LLC-1 cells) following TTFields application and an intraperitoneal (IP) injection of anti-PD-1 (⍺PD-1) was measured using Vernier calipers.20
References: 1. Karanam NK, Story MD. An overview of potential novel mechanisms of action underlying tumor treating fields-induced cancer cell death and their clinical implications. Int J Radiat Biol. 2021;97(8):1044-1054. doi:10.1080/09553002.2020.1837984 2. Mun EJ, Babiker HM, Weinberg U, Kirson ED, Von Hoff DD. Tumor-treating fields: a fourth modality in cancer treatment. Clin Cancer Res. 2018;24(2):266-275. doi:10.1158/1078-0432.CCR-17-1117 3. Rominiyi O, Vanderlinden A, Clenton SJ, Bridgewater C, Al-Tamimi Y, Collis SJ. Tumour treating fields therapy for glioblastoma: current advances and future directions. Br J Cancer. 2021;124(4):697-709. doi:10.1038/s41416-020-01136-5 4. Pless M, Droege C, von Moos R, Salzberg M, Betticher D. A phase I/II trial of tumor treating fields (TTFields) therapy in combination with pemetrexed for advanced non-small cell lung cancer. Lung Cancer. 2013;81(3):445-450. doi:10.1016/j.lungcan.2013.06.025 5. Novocure. Pivotal, open-label, randomized study of radiosurgery with or without tumor treating fields (TTFields) for 1-10 brain metastases from non-small cell lung cancer (NSCLC). Clinical Trials. Accessed June 21, 2022. https://clinicaltrials.gov/ct2/show/NCT02831959 6. Rivera F, Benavides M, Gallego J, Guillen-Ponce C, Lopez-Martin J, Küng M. Tumor treating fields in combination with gemcitabine or gemcitabine plus nab-paclitaxel in pancreatic cancer: results of the PANOVA phase 2 study. Pancreatology. 2019;19(1):64-72. doi:10.1016/j.pan.2018.10.004 7. Novocure. Effect of tumor treating fields (TTFields, 150 kHz) as front-line treatment of locally-advanced pancreatic adenocarcinoma concomitant with gemcitabine and nab-paclitaxel (PANOVA-3). Clinical Trials. Accessed June 21, 2022. https://clinicaltrials.gov/ct2/show/NCT03377491 8. Vergote I, von Moos R, Manso L, Van Nieuwenhuysen E, Concin N, Sessa C. Tumor treating fields in combination with paclitaxel in recurrent ovarian carcinoma: results of the INNOVATE pilot study. Gynecol Oncol. 2018;150(3):471-477. doi:10.1016/j.ygyno.2018.07.018 9. Novocure. Effect of tumor treating fields (TTFields, 200 kHz) concomitant with weekly paclitaxel for the treatment of recurrent ovarian cancer (ENGOT-ov50 / GOG-3029 / INNOVATE-3). Clinical Trials. Accessed June 21, 2022. https://clinicaltrials.gov/ct2/show/NCT03940196 10. Lavi-Shahaf G, Giladi M, Schneiderman RS, et al. Pooled analysis of response markers in cancer cell lines treated with tumor treating fields. Poster presented at: AACR Annual Meeting; March 29-April 3, 2019; Atlanta, GA. 11. Stupp R, Taillibert S, Kanner A, et al. Effect of tumor-treating fields plus maintenance temozolomide vs maintenance temozolomide alone on survival in patients with glioblastoma: a randomized clinical trial. JAMA. 2017;318(23):2306-2316. doi:10.1001/jama.2017.18718 12. Michelhaugh SK, Mittal S. Combined in vitro TTFields and paclitaxel reduce proliferation and clonogenicity in non-small cell lung cancer (NSCLC) cells from a patient previously treated with standard-of-care. Poster presented at: AACR Annual Meeting 2020; April 27-28 and June 22-24, 2020; Philadelphia, PA. 13. Voloshin T, Munster M, Blatt R, et al. Alternating electric fields (TTFields) in combination with paclitaxel are therapeutically effective against ovarian cancer cells in vitro and in vivo. Int J Cancer. 2016;139(12):2850-2858. doi:10.1002/ijc.30406 14. Karanam NK, Srinivasan K, Ding L, Sishc B, Saha D, Story MD. Tumor-treating fields elicit a conditional vulnerability to ionizing radiation via the downregulation of BRCA1 signaling and reduced DNA double-strand break repair capacity in non-small cell lung cancer cell lines. Cell Death Dis. 2017;8(3):1-10. doi:10.1038/cddis.2017.136 15. Silginer M, Weller M, Stupp R, Roth P. Biological activity of tumor-treating fields in preclinical glioma models. Cell Death Dis. 2017;8(4):e2753. doi:10.1038/cddis.2017.171 16. Karanam NK, Ding L, Aroumougame A, Story MD. Tumor treating fields cause replication stress and interfere with DNA replication fork maintenance: implications for cancer therapy. Transl Res. 2020;217:33-46. doi:10.1016/j.trsl.2019.10.003 17. Jo Y, Oh G, Gi Y, et al. Tumor treating fields (TTF) treatment enhances radiation-induced apoptosis in pancreatic cancer cells. Int J Radiat Biol. 2020;96(12):1528-1533. doi:10.1080/09553002.2020.1838658 18. Kim EH, Kim YJ, Song HS, et al. Biological effect of an alternating electric field on cell proliferation and synergistic antimitotic effect in combination with ionizing radiation. Oncotarget. 2016;7(38):62267-62279. doi:10.18632/oncotarget.11407 19. Giladi M, Munster M, Schneiderman RS, et al. Tumor treating fields (TTFields) delay DNA damage repair following radiation treatment of glioma cells. Radiat Oncol. 2017;12(1):1-13. doi:10.1186/s13014-017-0941-6 20. Voloshin T, Kaynan N, Davidi S, et al. Tumor-treating fields (TTFields) induce immunogenic cell death resulting in enhanced antitumor efficacy when combined with anti-PD-1 therapy. Cancer Immunol Immunother. 2020;69(7):1191-1204. doi:10.1007/s00262-020-02534-7