Phase I study of lurbinectedin in combination with weekly paclitaxel with or without bevacizumab in patients with advanced solid tumors Journal Article
| Authors: | Calvo, E.; Sessa, C.; Harada, G.; de Miguel, M.; Kahatt, C.; Luepke-Estefan, X. E.; Siguero, M.; Fernandez-Teruel, C.; Cullell-Young, M.; Stathis, A.; Drilon, A. |
| Article Title: | Phase I study of lurbinectedin in combination with weekly paclitaxel with or without bevacizumab in patients with advanced solid tumors |
| Abstract: | Lurbinectedin and paclitaxel showed synergism in preclinical studies and have non-completely overlapping toxicity profiles. This phase I trial evaluated a combination of paclitaxel and lurbinectedin with/without bevacizumab in advanced tumors. This trial was divided into Group A, which evaluated weekly paclitaxel (60 or 80 mg) plus lurbinectedin (3.0–5.0 mg flat dose [FD] or 2.2 mg/m2) every 3 weeks in advanced solid tumors; and Group B, which evaluated bevacizumab (BEV, 15 mg/kg) added to the recommended dose (RD) defined in Group A in advanced epithelial ovarian or non-small cell lung cancer (NSCLC). 67 patients (A, n = 55; B, n = 12) were treated. The RD was paclitaxel 80 mg/m2 on Day (D)1,D8 plus lurbinectedin 2.2 mg/m2 on D1. At this RD, myelotoxicity was reversible and manageable, and most non-hematological toxicities were mild/moderate. Adding BEV did not notably change tolerability. Twenty-five confirmed responses were observed: 20/51 evaluable patients in Group A (overall response rate [ORR] = 39% at all dose levels and at the RD), and 5/10 evaluable patients in Group B (ORR = 50%). Most responders had breast (n = 7/12 patients), small cell lung (SCLC) (n = 5/7), epithelial ovarian (n = 3/9) and endometrial cancer (n = 3/11) in Group A, and epithelial ovarian (n = 3/4) and NSCLC (n = 2/6) in Group B. Clinical benefit rate was 61% in Group A (58% at the RD), and 90% in Group B. No major pharmacokinetic drug-drug interactions were observed. Paclitaxel/lurbinectedin and paclitaxel/lurbinectedin/BEV are feasible combinations. Further development is warranted of paclitaxel/lurbinectedin in SCLC, breast, and endometrial cancer, and of paclitaxel/lurbinectedin/BEV in epithelial ovarian cancer. © 2022, The Author(s). |
| Keywords: | adult; treatment outcome; treatment response; aged; major clinical study; clinical trial; constipation; drug tolerability; fatigue; neutropenia; bevacizumab; advanced cancer; diarrhea; drug safety; hypertension; recommended drug dose; risk benefit analysis; side effect; paclitaxel; antineoplastic agent; endometrial neoplasms; endometrium cancer; multiple cycle treatment; sensory neuropathy; breast cancer; anemia; nausea; thrombocytopenia; vomiting; antineoplastic combined chemotherapy protocols; carcinoma, non-small-cell lung; lung neoplasms; abdominal abscess; creatinine; creatinine blood level; pathology; alanine aminotransferase blood level; aspartate aminotransferase blood level; drug dose escalation; febrile neutropenia; lung embolism; lung tumor; alanine aminotransferase; alkaline phosphatase; aspartate aminotransferase; maculopapular rash; ovary carcinoma; creatine kinase; sex difference; alkaline phosphatase blood level; age distribution; maximum tolerated dose; phase 1 clinical trial; dyspepsia; alopecia; epistaxis; endometrium tumor; dysgeusia; creatine kinase blood level; small cell lung cancer; non small cell lung cancer; decreased appetite; phase i study; response evaluation criteria in solid tumors; humans; human; male; female; article; lurbinectedin |
| Journal Title: | Investigational New Drugs |
| Volume: | 40 |
| Issue: | 6 |
| ISSN: | 0167-6997 |
| Publisher: | Springer |
| Date Published: | 2022-12-01 |
| Start Page: | 1263 |
| End Page: | 1273 |
| Language: | English |
| DOI: | 10.1007/s10637-022-01281-z |
| PUBMED: | 35947247 |
| PROVIDER: | scopus |
| PMCID: | PMC9652263 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 December 2022 -- Source: Scopus |
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