Oncology Daily Report: 01/30/2024

Phase 2 Studies

Chronic Lymphocytic Leukemia

A phase 2 open-label, multicenter study investigated the effect of venetoclax in 158 patients with del(17p) chronic lymphocytic leukemia and found that after a median follow-up of 70 months, the best objective response rate (ORR) was 77% (21% complete remission, 49% partial remission), with a median duration of response (DOR) of 39.3 months (1). The median progression-free survival (PFS) was 28.2 months, and median overall survival (OS) was 62.5 months, with 16% of patients remaining on treatment after 6 years. This study, part of the M13-982 trial (NCT01889186), demonstrates the long-term benefits of venetoclax for patients with del(17p) CLL, including those previously untreated or with relapsed/refractory disease.

Reference

Stilgenbauer S, Tausch E, Roberts AW, Davids MS, Eichhorst B, Hallek MJ, Hilmen P, Schneider C, Schetelig J, Böttcher S, Kater AP, Jiang Y, Boyer M, Popovic R, Ghanim MT, Moran M, Sinai WJ, Wang X, Mukherjee N, Chyla B, Wierda WG, Seymour JF. Six-year follow-up and subgroup analyses of a phase 2 trial of venetoclax for del(17p) chronic lymphocytic leukemia. Blood Adv. 2024 Jan 30:bloodadvances.2023011741. doi: 10.1182/bloodadvances.2023011741. Epub ahead of print. PMID: 38290108.

Colorectal Cancer (Metastatic)

A phase II randomized study investigated the effect of panitumumab in 248 patients with RAS wild-type metastatic colorectal cancer and found that hyperselection of wild-type tumors was associated with longer median progression-free survival (PFS) (9.2 vs. 6.0 months; HR=0.66, P=0.02) and overall survival (OS) (36.9 vs. 24.9 months; HR=0.91, P=0.50) compared to hyperselection mutant tumors when added to a FU/FA maintenance therapy (1). The study, part of the PanaMa trial (AIO KRK 0212), conducted in multiple centers, highlighted the potential of extended molecular profiling in improving patient selection for anti-EGFR containing maintenance regimens.

Reference

Stahler A, Kind AJ, Sers C, Mamlouk S, Müller L, Karthaus M, Frühauf S, Graeven U, Fischer von Weikersthal L, Sommerhäuser G, Kasper S, Hoppe B, Kurreck A, Held S, Heinemann V, Horst D, Jarosch A, Stintzing S, Trarbach T, Modest DP. Negative hyperselection of resistance mutations for panitumumab maintenance in RAS wild-type metastatic colorectal cancer (PanaMa phase II trial, AIO KRK 0212). Clin Cancer Res. 2024 Jan 30. doi: 10.1158/1078-0432.CCR-23-3023. Epub ahead of print. PMID: 38289994.

Hepatocellular Carcinoma

A phase II single-arm study investigated the effect of lenvatinib, sintilimab plus transarterial chemoembolization (Len-Sin-TACE) in 30 patients with BCLC stage C hepatocellular carcinoma and found a median progression-free survival (PFS) of 8.0 months, an objective response rate of 60.0%, a disease control rate of 86.7%, and a median overall survival of 18.4 months (1). Treatment-related adverse events occurred in 93.3% of patients, with grade 3 events in 40.0%.

Reference

Cai M, Huang W, Liang W, Guo Y, Liang L, Lin L, Xie L, Zhou J, Chen Y, Cao B, Wu J, Zhu K. Lenvatinib, sintilimab plus transarterial chemoembolization for advanced stage hepatocellular carcinoma: A phase II study. Liver Int. 2024 Jan 30. doi: 10.1111/liv.15831. Epub ahead of print. PMID: 38291865.

Myelofibrosis

A phase 2 study investigated the effect of add-on parsaclisib in 74 patients with primary or secondary myelofibrosis with suboptimal response to ruxolitinib and found that 28% of patients receiving daily-to-weekly dosing and 59.5% of patients receiving all-daily dosing achieved a ≥10% decrease in spleen volume at 12 weeks (1). Additionally, proportions of patients achieving ≥50% decrease at week 12 in symptom scores were 14% and 18% for daily-to-weekly dosing, and 28% and 32% for all-daily dosing, respectively. The study highlights parsaclisib's efficacy in reducing splenomegaly and improving symptoms with manageable toxicity.

Reference

Yacoub A, Borate U, Rampal RK, Ali H, Wang ES, Gerds AT, Hobbs GS, Kremyanskaya M, Winton EF, O'Connell C, Goel S, Oh ST, Schiller GJ, McCloskey J, Palmer JM, Holmes H, Hager S, Assad A, Erickson-Viitanen S, Zhou F, Daver NG. Phase 2 study of add-on parsaclisib in myelofibrosis patients with suboptimal response to ruxolitinib: Final results. Blood Adv. 2024 Jan 30:bloodadvances.2023011620. doi: 10.1182/bloodadvances.2023011620. Epub ahead of print. PMID: 38290135.

Phase 1 Studies

Ovarian Cancer (Recurrent)

A phase 1b study investigated the effect of PARP and MEK inhibition, with or without anti-PD-L1, in patients with BRCA wild-type, platinum-sensitive, recurrent ovarian cancer. The study found an objective response rate (ORR) of 35% with the doublet regimen (n=37) and 27% with the triplet regimen (n=37), and median progression-free survival (PFS) was 6.0 and 7.4 months, respectively (1). Tolerability was consistent with the known profiles of individual agents.

Reference

Mutch D, Voulgari A, Chen XM, Bradley WH, Oaknin A, Perez Fidalgo JA, Montosa FG, Herraez AC, Holloway RW, Powell MA, Nowicka M, Schaefer G, Merchant M, Yan Y. Primary results and characterization of patients with exceptional outcomes in a phase 1b study combining PARP and MEK inhibition, with or without anti-PD-L1, for BRCA wild-type, platinum-sensitive, recurrent ovarian cancer. Cancer. 2024 Jan 30. doi: 10.1002/cncr.35222. Epub ahead of print. PMID: 38288862.