FDA Rolls Out More New Indications for Existing Agents

Breast Cancer

• Ado-trastuzumab emtansine (Kadcycla^®) for early breast cancer (https://voice.ons.org/news-and-views/fda-approves-ado-trastuzumab-emtansine-for-early-breast-cancer)
  • Approval is for those with a HER2-positive early-stage breast cancer who have residual invasive disease after neoadjuvant taxane and trastuzumab-based treatment. 
  • Common adverse reactions are fatigue, nausea, increased transaminases, musculoskeletal pain, hemorrhage, thrombocytopenia, headache, peripheral neuropathy and arthralgia.
  • Recommended dose is 3.6 mg/kg via IV infusion every three weeks for a total of 14 cycles.
• Alpelisib (Piqray^®) for metastatic breast cancer (https://voice.ons.org/news-and-views/fda-approves-alpelisib-for-metastatic-breast-cancer)
  • Approval is in combination with fulvestrant for men and women with HR-positive, HER2-negative, MIK3CA-mutated advanced or metastatic breast cancer. 
  • Common adverse events are hyperglycemia, elevated creatinine, diarrhea, rash, decreased lymphocyte count, nausea, and fatigue.
  • Recommended dose is 300 mg orally once daily with food. 

Head and Neck Cancer

• Pembrolizumab (Keytruda^®) for metastatic or unresectable recurrent head and neck squamous cell carcinoma (https://voice.ons.org/news-and-views/fda-approves-pembrolizumab-for-first-line-treatment-of-hnscc)
  • Approval is either as single agent or in combination with platinum and fluorouracil for patients with PD-L1-positive metastatic or unresectable head and neck squamous cell carcinoma.
  • Most common adverse events are fatigue, constipation, and rash. Patients also experienced fatigue, constipation, vomiting, mucosal inflammation, diarrhea, decreased appetite, stomatitis, and cough with pembrolizumab plus chemotherapy. Immune-related adverse events should be considered for all checkpoint inhibitors.
  • Recommended dose is 200 mg via IV over 30 minutes every three weeks.

Hematologic Cancer

• Ivosidenib (Tivsovo^®) for first-line, IDH1-positive acute myeloid leukemia (https://voice.ons.org/news-and-views/fda-approves-ivosidenib-as-first-line-treatment-for-aml-with-idh1-mutation)
  • Approval is for adults aged 75 years or older who express the IDH1 mutation or those who have a comorbidities that preclude them from intensive induction chemotherapy.
  • Common adverse reactions are diarrhea, fatigue, edema, decreased appetite, leukocytosis, nausea, arthralgia, and abdominal pain.
  • Recommended dose is 500 mg orally once daily with or without food.
• Venetoclax (Venclexta^®) for chronic lymphocytic leukemia and small lymphocytic lymphoma (https://voice.ons.org/news-and-views/fda-approves-venetoclax-for-cll-and-sll)
  • Common adverse events are neutropenia, thrombocytopenia, anemia, diarrhea, nausea, upper-respiratory tract infection, cough, musculoskeletal pain, fatigue, and edema.
  • Recommended dosing varies by indication, concomitant medications, and changes throughout a cycle. Refer to the package insert for dosing details.  
• Lenalidomide (Revlimid^®) for follicular and marginal zone lymphoma (https://voice.ons.org/news-and-views/fda-approves-lenalidomide-for-follicular-and-marginal-zone-lymphoma)
  • Approval is for lenalidomide in combination with a rituximab product.
  • Common adverse events include neutropenia, fatigue, diarrhea, constipation, nausea, and cough. Black box warnings include risk of embryo-fetal toxicity, hematologic toxicity, and venous and arterial thromboembolism. 
  • Recommended dose is 20 mg orally on days 1–21 of a 28-day cycle for up to 12 cycles.

• Polatuzumab vedotin-piiq (Polivy™) for diffuse large B-cell lymphoma (https://voice.ons.org/news-and-views/fda-approves-polatuzumab-vedotin-piiq-for-diffuse-large-b-cell-lymphoma)
  • Approval is for adults in combination with bendamustine and a rituximab product after at least two prior therapies.
  • Common adverse events observed while on all three agents include neutropenia, thrombocytopenia, anemia, peripheral neuropathy, fatigue, diarrhea, pyrexia, decreased appetite, and pneumonia. 
  • Recommended dose is 1.8 mg/kg via IV over 90 minutes every 21 days for six cycles.
• Daratumumab (Darzalex^®) for multiple myeloma (https://voice.ons.org/news-and-views/fda-approves-daratumumab-for-multiple-myeloma-ineligible-for-autologous-stem-cell) when ineligible for autologous stem cell transplantation
  • Approval is in combination with lenalidomide and dexamethasone for patients unable to pursue autologous stem cell transplantation. 
  • Common adverse events are infusion reactions, diarrhea, constipation, nausea, peripheral edema, fatigue, back pain, asthenia, pyrexia, upper-respiratory tract infection, and pneumonia. 
  • Recommended dose is 16 mg/kg, but the schedule varies throughout treatment. Refer to package insert for dosing details. Pre- and postinfusion medications are needed.

Lung Cancer

• Pembrolizumab (Keytuda^®) for metastatic small cell lung cancer (https://voice.ons.org/news-and-views/fda-approves-pembrolizumab-for-metastatic-small-cell-lung-cancer)
  • Approval is for patients with metastatic small cell lung cancer with disease progression on or after platinum-based chemotherapy and at least one other prior line of therapy. 
  • Adverse reactions include fatigue, decreased appetite, cough, nausea, and constipation. Immune related adverse events should be considered for all checkpoint inhibitors. 
  • Recommended dose is 200 mg via IV over 30 minutes every three weeks.

Renal Cell Carcinoma

• Pembrolizumab (Keytuda^®) plus axitinib (Inlyta^®) for advanced renal cell carcinoma (https://voice.ons.org/news-and-views/fda-approves-pembrolizumab-plus-axitinib-for-advanced-renal-cell-carcinoma)
  • Approval is for first-line treatment of advanced renal cell carcinoma that does not have to be PD-L1 positive. 
  • Common adverse events are hepatotoxicity, diarrhea, fatigue, hypertension, hypothyroidism, decreased appetite, and palmar-plantar erythrodysesthesia. Immune-related adverse events should be considered for all checkpoint inhibitors.
  • Recommended dosing is pembrolizumab 200 mg every three weeks and axtitinib 5 mg orally twice daily.
• Avelumab (Bavencio^®) plus axitinib (Inlyta^®) for renal cell carcinoma (https://voice.ons.org/news-and-views/fda-approves-avelumab-plus-axitinib-for-renal-cell-carcinoma)
  • Approval is for first-line treatment of advanced renal cell carcinoma that does not have to be PD-L1 positive.
  • Common adverse events are diarrhea, fatigue, hypertension, musculoskeletal pain, nausea, mucositis, and palmar-plantar erythrodysesthesia. Immune-related adverse events should be considered for all checkpoint inhibitors.
  • Recommended dosing is avelumab 800 mg every two weeks and axitinib 5 mg orally twice daily. 

With the influx of oral treatments used as single-agent therapies as well as part of multidrug regimens, refer to ONS’s variety of oral therapy resources, including patient education sheets (http://oralchemoedsheets.com/) and an oral adherence toolkit (https://www.ons.org/toolkits/oral-adherence-toolkit).