Oncology Daily Update: 01/20/2024

Phase 3 Studies

Endometrial Cancer (Advanced)

The phase III DUO-E trial, a global, double-blind, placebo-controlled study, evaluated durvalumab plus carboplatin/paclitaxel followed by maintenance durvalumab with or without olaparib as first-line treatment in 718 patients with advanced or recurrent endometrial cancer (1). The trial found statistically significant progression-free survival (PFS) benefits in both durvalumab (HR, 0.71) and durvalumab + olaparib arms (HR, 0.55) compared to control. The treatment demonstrated a meaningful PFS benefit, especially in mismatch repair (MMR)-deficient and MMR-proficient disease subgroups.

Reference

Westin SN, Moore K, Chon HS, Lee JY, Thomes Pepin J, Sundborg M, Shai A, de la Garza J, Nishio S, Gold MA, Wang K, McIntyre K, Tillmanns TD, Blank SV, Liu JH, McCollum M, Contreras Mejia F, Nishikawa T, Pennington K, Novak Z, De Melo AC, Sehouli J, Klasa-Mazurkiewicz D, Papadimitriou C, Gil-Martin M, Brasiuniene B, Donnelly C, Del Rosario PM, Liu X, Van Nieuwenhuysen E; DUO-E Investigators. Durvalumab Plus Carboplatin/Paclitaxel Followed by Maintenance Durvalumab With or Without Olaparib as First-Line Treatment for Advanced Endometrial Cancer: The Phase III DUO-E Trial. J Clin Oncol. 2024 Jan 20;42(3):283-299. doi: 10.1200/JCO.23.02132. Epub 2023 Oct 21. PMID: 37864337.

Myelodysplastic Syndromes

The phase 3 IMerge trial, a multinational, randomized, double-blind, placebo-controlled study, investigated imetelstat in patients with lower-risk myelodysplastic syndromes who were relapsed or refractory to erythropoiesis-stimulating agents (1). The study involved 178 patients and found that 40% of patients in the imetelstat group achieved red blood cell transfusion independence for at least 8 weeks, compared to 15% in the placebo group. Grade 3-4 treatment-emergent adverse events were significantly higher in the imetelstat group, predominantly neutropenia and thrombocytopenia.

Reference

Platzbecker U, Santini V, Fenaux P, Sekeres MA, Savona MR, Madanat YF, Díez-Campelo M, Valcárcel D, Illmer T, Jonášová A, Bělohlávková P, Sherman LJ, Berry T, Dougherty S, Shah S, Xia Q, Sun L, Wan Y, Huang F, Ikin A, Navada S, Feller F, Komrokji RS, Zeidan AM. Imetelstat in patients with lower-risk myelodysplastic syndromes who have relapsed or are refractory to erythropoiesis-stimulating agents (IMerge): a multinational, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2024 Jan 20;403(10423):249-260. doi: 10.1016/S0140-6736(23)01724-5. Epub 2023 Dec 1. Erratum in: Lancet. 2024 Jan 20;403(10423):248. PMID: 38048786.

Small-Cell Lung Cancer (Extensive-Stage)

A phase III randomized controlled study investigated the effect of tiragolumab in combination with atezolizumab plus chemotherapy in 490 patients with untreated extensive-stage small-cell lung cancer (1). The final analysis showed that the addition of tiragolumab did not reach statistical significance in progression-free survival (PFS) (median, 5.4 months tiragolumab vs. 5.6 months control) or overall survival (OS) (median, 13.1 months in both arms). The combination was well tolerated with no new safety signals.

Reference

Rudin CM, Liu SV, Soo RA, Lu S, Hong MH, Lee JS, Bryl M, Dumoulin DW, Rittmeyer A, Chiu CH, Ozyilkan O, Johnson M, Navarro A, Novello S, Ozawa Y, Tam SH, Patil NS, Wen X, Huang M, Hoang T, Meng R, Reck M. SKYSCRAPER-02: Tiragolumab in Combination With Atezolizumab Plus Chemotherapy in Untreated Extensive-Stage Small-Cell Lung Cancer. J Clin Oncol. 2024 Jan 20;42(3):324-335. doi: 10.1200/JCO.23.01363. Epub 2023 Nov 17. PMID: 37976444.

Phase 2 Studies

Acute Lymphoblastic Leukemia (Philadelphia Chromosome-Negative B-Precursor)

A phase II open-label, multicenter study (INITIAL-1 trial) investigated the effect of inotuzumab ozogamicin and dexamethasone as induction therapy in 45 patients older than 55 years with newly diagnosed, CD22-positive, BCR::ABL-negative B-precursor ALL (1). Results showed all patients achieved complete remission, with event-free survival at one and three years being 88% and 55%, respectively, and overall survival (OS) being 91% and 73%. The treatment was well tolerated, indicating a rationale for integrating inotuzumab ozogamicin into first-line regimens for older patients with B-ALL.

Reference

Stelljes M, Raffel S, Alakel N, Wäsch R, Kondakci M, Scholl S, Rank A, Hänel M, Spriewald B, Hanoun M, Martin S, Schwab K, Serve H, Reiser L, Knaden J, Pfeifer H, Marx J, Sauer T, Berdel WE, Lenz G, Brüggemann M, Gökbuget N, Wethmar K. Inotuzumab Ozogamicin as Induction Therapy for Patients Older Than 55 Years With Philadelphia Chromosome-Negative B-Precursor ALL. J Clin Oncol. 2024 Jan 20;42(3):273-282. doi: 10.1200/JCO.23.00546. Epub 2023 Oct 26. PMID: 37883727.

Ovarian Cancer (Platinum-Resistant)

A phase II umbrella trial, KGOG 3045, open-label and investigator-initiated, studied the efficacy and safety of durvalumab with or without tremelimumab plus chemotherapy in patients with platinum-resistant recurrent ovarian cancer lacking homologous recombination repair gene mutations (1). The study enrolled 58 patients, with objective response rates of 20.0%, 33.3%, 29.4%, and 22.2% in different arms. Adding tremelimumab to durvalumab and chemotherapy improved progression-free survival, with manageable treatment-related adverse events.

Reference

Kim SI, Joung JG, Kim YN, Park J, Park E, Kim JW, Lee S, Lee JB, Kim S, Choi CH, Kim HS, Lim J, Chung J, Kim BG, Lee JY. Durvalumab with or without tremelimumab plus chemotherapy in HRR non-mutated, platinum-resistant ovarian cancer (KGOG 3045): A phase II umbrella trial. Gynecol Oncol. 2024 Jan 20;182:7-14. doi: 10.1016/j.ygyno.2023.12.029. Epub ahead of print. PMID: 38246047.

Ovarian Cancer (Platinum-Resistant)

The phase II OCTOVA trial compared the efficacy of olaparib versus weekly paclitaxel or olaparib + cediranib in recurrent ovarian cancer (1). The study enrolled 139 participants and found that progression-free survival (PFS) was increased for olaparib + cediranib versus olaparib alone, but there was no difference between weekly paclitaxel and olaparib. The main treatment-related adverse events in the olaparib + cediranib arm were manageable diarrhea and hypertension.

Reference

Nicum S, McGregor N, Austin R, Collins L, Dutton S, McNeish I, Glasspool R, Hall M, Roux R, Michael A, Clamp A, Jayson G, Kristeleit R, Banerjee S, Mansouri A. Results of a randomised Phase II trial of olaparib, chemotherapy or olaparib and cediranib in patients with platinum-resistant ovarian cancer. Br J Cancer. 2024 Jan 20. doi: 10.1038/s41416-023-02567-6. Epub ahead of print. PMID: 38245661.

Renal Cell Carcinoma (Advanced)

A randomized phase II trial (PRISM) compared standard versus modified ipilimumab, in combination with nivolumab, in 192 patients with advanced renal cell carcinoma (1). The modified regimen (once every 12 weeks) resulted in significantly lower incidence of grade 3-5 treatment-related adverse events (trAEs) (32.8% vs. 53.1%) compared to the standard regimen (once every 3 weeks). The 12-month progression-free survival (PFS) using modified ipilimumab was 46.1%, with an overall response rate of 45.3% in the modified group versus 35.9% in the standard group.

Reference

Vasudev NS, Ainsworth G, Brown S, Pickering L, Waddell T, Fife K, Griffiths R, Sharma A, Katona E, Howard H, Velikova G, Maraveyas A, Brown J, Pezaro C, Tuthill M, Boleti E, Bahl A, Szabados B, Banks RE, Brown J, Venugopal B, Patel P, Jain A, Symeonides SN, Nathan P, Collinson FJ, Powles T. Standard Versus Modified Ipilimumab, in Combination With Nivolumab, in Advanced Renal Cell Carcinoma: A Randomized Phase II Trial (PRISM). J Clin Oncol. 2024 Jan 20;42(3):312-323. doi: 10.1200/JCO.23.00236. Epub 2023 Nov 6. PMID: 37931206.

Cervical Cancer

A phase 2, 1:1 randomized, investigator-blinded, controlled, non-inferiority trial compared hypofractionated versus standard chemoradiotherapy in the treatment of uterine cervix cancer (1). The study, which reported interim results after 50% accrual, found no significant difference in complete clinical response (CCR) at 3 months between the two groups, but a higher rate of acute gastrointestinal toxicity in the hypofractionated group.

Reference

Maddah Safaei A, Esmati E, Gomar M, Akhavan S, Sheikh Hasani S, Malekzadeh Moghani M, Zamani N, Moshtaghi M, Malek M, Jafari F, Sharifian A, Kolahdouzan K. Hypofractionated versus standard chemoradiotherapy in the definitive treatment of uterine cervix cancer: interim results of a randomized controlled clinical trial. J Cancer Res Clin Oncol. 2024 Jan 20;150(1):20. doi: 10.1007/s00432-023-05563-8. PMID: 38244105; PMCID: PMC10799776.