Clinical Edge

Summaries of Must-Read Clinical Literature, Guidelines, and FDA Actions

Outcomes after cross-over to regorafenib in advanced non-adipocytic soft tissue sarcoma

Brodowicz T et al. European Journal of Cancer 2018: 99; 28-36. https://doi.org/10.1016/j.ejca.2018.05.008

Key clinical point: Regorafenib warrants further clinical investigation in refractory non-adipocytic sarcomas, based on an updated analysis of the patients who crossed over from placebo to active drug in the placebo-controlled, phase-2 REGOSARC trial.

Main finding: The progression-free survival (PFS) benefit of regorafenib as compared to placebo was confirmed with longer follow-up (HR = 0.50; 95% CI: 0.35–0.71; P less than .0001). Overall survival was not significantly different (HR = 0.78; 0.54–1.12; P = .18); however, 55 of 68 patients who progressed on placebo (81%) received cross-over regorafenib after progression and 59% of them had a growth modulation index of at least 1.3 (95% CI, 45–71%). Delayed start of regorafenib was associated with a statistically non-significant shorter PFS as compared to early treatment (HR = 1.21; 0.84–1.73; P = .30) without impact on overall survival.

Study details: From June 2013 to December 2014, 139 patients were enrolled in the non-adipocytic sarcoma cohorts. Median follow-up is now 32.4 months. In the placebo arm, intra-patient benefit of regorafenib after cross-over was evaluated by the growth modulation index (PFS after cross-over regorafenib divided by PFS with placebo). The activity of delayed (after cross-over) vs. early (at study entry) regorafenib was evaluated by comparing PFS after cross-over to regorafenib to PFS after randomisation in the regorafenib arm.

Disclosures: The study was supported by Bayer HealthCare. The authors declared no relevant financial conflicts of interest.

Source: Brodowicz T et al. European Journal of Cancer 2018: 99; 28-36. https://doi.org/10.1016/j.ejca.2018.05.008

Citation:

Brodowicz T et al. European Journal of Cancer 2018: 99; 28-36. https://doi.org/10.1016/j.ejca.2018.05.008

This Week's Must Reads

Case studies shed light on treatment for rare form of MCL , Mori S et al. Clin Lymphoma Myeloma Leuk. 2019 Feb;19(2):e93-7.

Histopathological clues for differentiating follicular lymphomas, Servitje O et al. J Cutan Pathol. 2019;46:182-9.

Single agent daratumumab is not an option in B-cell lymphomas, Salles G et al. Clin Lymphoma Myeloma Leuk. 2019 Jan 2. doi: 10.1016/j.clml.2018.12.013.

Ibrutinib combo advances in CNS lymphoma, Grommes C et al. Blood. 2019;133(5):436-45.

Best frontline options for advanced follicular lymphoma, Shah NN et al. Clin Lymphoma Myeloma Leuk. 2019 Feb;19(2):95-102.

Must Reads in Sarcoma & GIST

Intensity modulated radiation therapy may be preferable in children with extremity nonrhabdomyosarcoma soft-tissue sarcomas, Source: Rao A et al. Intl J Rad Oncology*Biology*Physics; Jan. 2019, 38-44. https://doi.org/10.1016/j.ijrobp.2018.09.005

Expanded genetic analyses of myxofibrosarcomas may guide precision therapies, Ogura K et al. Nature Communications; 17 July 2018. https://doi.org/10.1038/s41467-018-03891-9

Malignant tenosynovial giant cell tumors appear to originate from synoviocytes, Al-Ibraheemi A et al. Modern Pathology; 11 Sept. 2018. https://doi.org/10.1038/s41379-018-0129-0

Type and rate of clonal evolution vary widely in sarcoma pathogenetic subgroups, Hofvander J et al. Nature Communications 10 Sept. 2018. https://doi.org/10.1038/s41467-018-06098-0

Increasing pannexin 1 levels might be a novel treatment for rhabdomyosarcoma , Xiang X et al. Oncogenesis; 21 Nov. 2018. https://doi.org/10.1038/s41389-018-0100-4