Oncology Daily Report: 01/19/2024

Phase 2b Studies

Breast Cancer (Metastatic Hormone Receptor-Positive)

A randomized phase 2b trial investigated the effect of ipilimumab and nivolumab combined with anthracycline-based chemotherapy in 82 patients with metastatic hormone receptor-positive breast cancer (HR(+)mBC) (1). The study found that in the per-protocol population (N=78), median progression-free survival (PFS) in the immune-chemo arm was 5.1 months, compared to 3.6 months in the chemo-only arm, with a hazard ratio (HR) of 0.94 (95% CI 0.59 to 1.51). Clinical benefit rates were 55% (26/47) in the immune-chemo arm and 48% (15/31) in the chemo-only arm. In the cross-over arm (ipi/nivo-only), objective responses were observed in 19% of patients (3/16) and clinical benefit in 25% (4/16). High-grade immune-related adverse events were associated with prolonged PFS. The trial registration number is ClinicalTrials.gov Identifier: NCT03409198.

Reference

Andresen NK, Røssevold AH, Quaghebeur C, Gilje B, Boge B, Gombos A, Falk RS, Mathiesen RR, Julsrud L, Garred Ø, Russnes HG, Lereim RR, Chauhan SK, Lingjærde OC, Dunn C, Naume B, Kyte JA. Ipilimumab and nivolumab combined with anthracycline-based chemotherapy in metastatic hormone receptor-positive breast cancer: a randomized phase 2b trial. J Immunother Cancer. 2024 Jan 19;12(1):e007990. doi: 10.1136/jitc-2023-007990. PMID: 38242720; PMCID: PMC10806573.

Phase 2 Studies

Gastric/Esophagogastric Junction Cancer (HER2-positive resectable adenocarcinoma with extensive lymph node metastasis)

A randomized phase II trial, Japan Clinical Oncology Group Study JCOG1301C (TRIGGER study), investigated the addition of trastuzumab to neoadjuvant chemotherapy (NAC) with S-1 plus cisplatin (SP) for HER2-positive gastric or esophagogastric junction cancer (1). The study included 46 patients, split between SP alone (arm A, 22 patients) and SP plus trastuzumab (arm B, 24 patients). Results showed an objective response rate of 50% in arm A and 84% in arm B, with R0 resection rates of 91% and 92%, and pathological response rates (≥ grade 1b in Japanese classification) of 23% and 50% respectively. The study concluded that trastuzumab safely enhances antitumor activity when added to platinum-containing doublet chemotherapy as NAC for this cancer type.

Reference

Tokunaga M, Machida N, Mizusawa J, Ito S, Yabusaki H, Hirao M, Watanabe M, Imamura H, Kinoshita T, Yasuda T, Hihara J, Fukuda H, Yoshikawa T, Boku N, Terashima M. Early endpoints of a randomized phase II trial of preoperative chemotherapy with S-1/CDDP with or without trastuzumab followed by surgery for HER2-positive resectable gastric or esophagogastric junction adenocarcinoma with extensive lymph node metastasis: Japan Clinical Oncology Group study JCOG1301C (Trigger Study). Gastric Cancer. 2024 Jan 19. doi: 10.1007/s10120-024-01467-9. Epub ahead of print. PMID: 38243037.

Hepatocellular Carcinoma (Resected high-risk with microvascular invasion)

A randomized, controlled, phase 2 trial conducted at six hospitals in China (Chinese Clinical Trial Registry identifier: ChiCTR2000037655) evaluated adjuvant sintilimab, a programmed cell death protein 1 inhibitor, in 198 patients with hepatocellular carcinoma (HCC) with microvascular invasion (MVI) (1). Patients were randomized into a sintilimab group (99 patients) or an active surveillance group (99 patients). Sintilimab significantly prolonged median recurrence-free survival (RFS) to 27.7 months compared to 15.5 months in the active surveillance group (hazard ratio 0.534, P = 0.002). 12.4% of patients in the sintilimab group experienced grade 3 or 4 treatment-related adverse events. The study supports the use of immune checkpoint inhibitors as effective adjuvant therapy in high-risk HCC patients.

Reference

Wang K, Xiang YJ, Yu HM, Cheng YQ, Liu ZH, Qin YY, Shi J, Guo WX, Lu CD, Zheng YX, Zhou FG, Yan ML, Zhou HK, Liang C, Zhang F, Wei WJ, Lau WY, Li JJ, Liu YF, Cheng SQ. Adjuvant sintilimab in resected high-risk hepatocellular carcinoma: a randomized, controlled, phase 2 trial. Nat Med. 2024 Jan 19. doi: 10.1038/s41591-023-02786-7. Epub ahead of print. PMID: 38242982.

Oropharyngeal Carcinoma (Human papillomavirus-related)

A phase II non-randomized study investigated the effect of de-escalated definitive chemoradiotherapy based on tumor hypoxia in 152 patients with T0-2/N1-N2c HPV-related oropharyngeal carcinoma (1). The study used (18)F-fluoromisonidazole positron emission tomography scans to guide treatment, with 128 patients receiving 30 Gy and 24 patients receiving 70 Gy. The 2-year locoregional control was 94.7%, with 2-year progression-free survival (PFS) and overall survival (OS) rates of 94% and 100%, respectively, for the 30-Gy cohort, and 96% for both PFS and OS in the 70-Gy cohort. The study concluded that tumor hypoxia is an effective criterion for directing chemoradiotherapy dosage, achieving similar efficacy with reduced toxicity.

Reference

Lee NY, Sherman EJ, Schöder H, Wray R, Boyle JO, Singh B, Grkovski M, Paudyal R, Cunningham L, Zhang Z, Hatzoglou V, Katabi N, Diplas BH, Han J, Imber BS, Pham K, Yu Y, Zakeri K, McBride SM, Kang JJ, Tsai CJ, Chen LC, Gelblum DY, Shah JP, Ganly I, Cohen MA, Cracchiolo JR, Morris LGT, Dunn LA, Michel LS, Fetten JV, Kripani A, Pfister DG, Ho AL, Shukla-Dave A, Humm JL, Powell SN, Li BT, Reis-Filho JS, Diaz LA, Wong RJ, Riaz N. Hypoxia-Directed Treatment of Human Papillomavirus-Related Oropharyngeal Carcinoma. J Clin Oncol. 2024 Jan 19:JCO2301308. doi: 10.1200/JCO.23.01308. Epub ahead of print. PMID: 38241600.