May 26, 2020
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FDA approves oncology, hematology therapies

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The FDA approved several therapies for oncology or hematology indications.

They include:

  • Niraparib (Zejula, GlaxoSmithKline) for first-line maintenance treatment of women with advanced epithelial ovarian, fallopian tube or primary peritoneal cancers who achieved complete or partial response to first-line platinum-based chemotherapy.

The FDA based the approval on results of the randomized phase 3 PRIMA trial, which included 733 women in complete or partial response to first-line platinum-based chemotherapy.

Researchers assigned the women to maintenance therapy with niraparib — a poly(ADP-ribose) polymerase (PARP) inhibitor — or placebo.

PFS — both in the homologous recombination deficient population and the overall study population — served as the main efficacy outcome.

Investigators reported statistically significant improvement in PFS among niraparib-treated women in the homologous recombination deficient group (21.9 months vs. 10.4 months; HR = 0.43; 95% CI, 0.31-0.59) and the overall cohort (13.8 months vs. 8.2 months; HR = 0.62; 95% CI, 0.5-0.76).

  • Ibrutinib (Imbruvica; Janssen, Pharmacyclics) in combination with rituximab (Rituxan; Genentech, Biogen) for treatment of newly diagnosed patients with chronic lymphocytic leukemia or small lymphocytic lymphoma.

The FDA based the approval on results of the phase 3 E1912 study, which included 529 patients aged 70 years or younger (median age, 58 years) with previously untreated CLL.

Researchers randomly assigned 354 patients to ibrutinib plus rituximab. The other 175 patients received standard chemoimmunotherapy with fludarabine, cyclophosphamide and rituximab.

After median follow-up of 37 months, a higher percentage of those treated with ibrutinib plus rituximab remained progression free (88% vs. 75%; HR = 0.34; 95% CI, 0.22-0.52).

  • Pemigatinib (Pemazyre, Incyte) for adults with previously treated locally advanced or metastatic, unresectable cholangiocarcinoma whose tumors have a fusion or other rearrangement of fibroblast growth factor receptor 2 (FGFR2).

Pemigatinib — which blocks FGFR2 in tumor cells to prevent them from growing or spreading — is the first targeted treatment for cholangiocarcinoma, a rare form of cancer that forms in the bile ducts.

The FDA based the approval on results of a trial that included 107 patients with locally advanced or metastatic cholangiocarcinoma with FGFR2 fusions or rearrangements who had received prior treatment.

Trial participants received pemigatinib once daily in a 14-days-on, 7-days-off schedule. Treatment continued until disease progression or unacceptable toxicity.

Researchers reported a 36% overall response rate, with 2.8% of patients achieving complete response and 33% achieving partial response.

Among the 38 patients who achieved response, 24 (63%) had responses that lasted at least 6 months and seven (18%) had responses that lasted at least 12 months.

  • Tucatinib (Tukysa, Seattle Genetics) in combination with chemotherapy for the treatment of certain adults with previously treated advanced HER2-positive breast cancer.
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The approval applies to use of tucatinib with trastuzumab (Herceptin, Genentech) and capecitabine for patients whose cancer can’t be removed with surgery or has spread to other parts of the body, and who received at least one prior anti-HER2-based regimen in the metastatic setting.

Tucatinib is an oral tyrosine kinase inhibitor that is highly selective for HER2 without significant inhibition of EGFR.

The FDA approved the agent based on results of the randomized phase 3 HER2CLIMB trial, which included 612 patients with HER2-positive advanced unresectable or metastatic breast cancer.

Researchers randomly assigned patients 2:1 to tucatinib dosed at 300 mg or placebo twice daily in combination with trastuzumab — dosed at 6 mg/kg once every 21 days, with a loading dose of 8 mg/kg on day 1 of the first cycle — and capecitabine, dosed at 1,000 mg/m2 twice daily on days 1 to 14 of each 21-day cycle.

Results showed longer median PFS (7.8 months vs. 5.6 months) and OS (21.9 months vs. 17.4 months) in the tucatinib group.

Researchers also reported longer median PFS with tucatinib among patients with brain metastases at baseline (7.6 months vs. 5.4 months).

  • Mitomycin gel (Jelmyto, UroGen Pharma) for treatment of low-grade upper tract urothelial cancer.

Mitomycin gel is an alkylating drug that inhibits the transcription of DNA into RNA, stopping protein synthesis and prohibiting the cancer cell from multiplying.

The FDA based its approval on results of the phase 3 OLYMPUS trial, which evaluated 71 patients with low-grade upper tract urothelial cancer who had not been previously treated for their disease. Complete response at 3 months after initiation of therapy served as the study’s primary endpoint.

Results showed 58% of patients (n = 41) achieved complete response after six weekly treatments of mitomycin gel. Nineteen of these patients (46%) continued to demonstrate complete response at 12 months.

  • Luspatercept-aamt (Reblozyl; Bristol-Myers Squibb, Acceleron), an erythroid maturation agent, to treat anemia among certain adults with lower-risk myelodysplastic syndrome.

The approval — the first in more than a decade for patients with myelodysplastic syndrome — authorizes use of luspatercept-aamt by adults with very low- to intermediate-risk myelodysplastic syndrome with ring sideroblasts or myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis who have anemia that failed an erythropoiesis stimulating agent and requires two or more red blood cell units over 8 weeks.

Guillermo Garcia-Manero
“Anemia is a serious consequence of myelodysplastic syndrome, requiring the majority of these patients to receive regular red blood cell transfusions, which can lead to additional complications, such as iron overload, transfusion site reactions and infections,” Guillermo Garcia-Manero, MD, professor and chief of the section of myelodysplastic syndrome in the department of leukemia at The University of Texas MD Anderson Cancer Center, said in a press release. “In our current environment, we are reminded of the significant burden frequent blood transfusions can have on individuals and the health care system.”
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The FDA based the approval on results of the randomized phase 3 MEDALIST study, which evaluated the efficacy and safety of luspatercept-aamt for patients with very low-, low- and intermediate-risk myelodysplastic syndrome who had ring sideroblasts but did not have deletion 5q.

A higher percentage of patients assigned luspatercept-aamt than placebo achieved independence from red blood cell transfusions for at least 8 weeks during the first 24 weeks of the trial, the study’s primary endpoint.

In addition, a significantly higher percentage of patients assigned luspatercept-aamt achieved at least 12 weeks of independence from transfusion within the first 24 weeks and first 48 weeks of the study.

  • Sacituzumab govitecan-hziy (Trodelvy, Immunomedics) for treatment of adults with metastatic triple-negative breast cancer who received at least two prior therapies for metastatic disease.

Sacituzumab govitecan-hziy is an antibody-drug conjugate directed against Trop-2, a cell-surface protein expressed in many solid cancers.

The FDA based the approval on results of the phase 2, multicenter, single-arm IMMU-132-01 trial, which included 108 patients with metastatic triple-negative breast cancer who received at least two prior treatments for metastatic disease.

Patients received sacituzumab govitecan-hziy dosed at 10 mg/kg via IV on days 1 and 8 every 21 days. Treatment continued until disease progression or patients became unable to tolerate therapy.

Investigator-assessed overall response rate and response duration served as primary efficacy outcome measures.

Researchers reported an ORR of 33.3% (95% CI, 24.6-43.1) and a median response duration of 7.7 months (95% CI, 4.9-10.8).

Aditya Bardia
“The approval of Trodelvy — the first antibody-drug conjugate approved specifically for metastatic triple-negative breast cancer, an aggressive cancer with a poor prognosis and few effective therapies — will give clinicians a novel tool for treating patients with this disease,” Aditya Bardia, MD, MPH, director of precision medicine at Center for Breast Cancer at Massachusetts General Hospital Cancer Center, assistant professor of medicine at Harvard Medical School and lead investigator of the IMMU-132-01 trial, said in a press release. “In our trial, Trodelvy demonstrated clinically meaningful responses in patients with difficult-to-treat metastatic triple-negative breast cancer and moves the needle toward better outcomes for patients with metastatic breast cancer.”