Patients with rare cancers like intrahepatic cholangiocarcinoma seldom have many additional treatment options if their tumors become resistant to first-line therapy: From August 1, 2021–July 31, 2022, the U.S. Food and Drug Administration approved only five new agents or indications for rare tumors. On September 30, 2022, FDA added one more, giving futibatinib (Lytgobi™) accelerated approval for adult patients with previously treated, unresectable, locally advanced or metastatic intrahepatic cholangiocarcinoma harboring fibroblast growth factor receptor 2 gene fusions or other rearrangements. The approval was based on the drug’s 42% overall response rate and median duration of response of 9.7 months.

On August 5, 2022, the U.S. Food and Drug Administration approved darolutamide (Nubeqa®) in combination with docetaxel in adults with metastatic hormone-sensitive prostate cancer. The approval was based on clinical trial findings demonstrating that the agent improved overall survival and significantly delayed time to pain progression compared to placebo.

More than 40% of adult patients with mismatch repair deficient recurrent or advanced endometrial cancer had an overall response receiving dostarlimab-gxly (Jemperli), and more than 90% of those lasted six months or longer during the drug’s clinical trials. Those results led the U.S. Food and Drug Administration to grant the agent its original accelerated approval in 2021 for the indication. FDA expanded the accelerated approval later that year to include all recurrent or advanced solid tumors with dMMR demonstrated through an FDA-approved diagnostic test.

When the U.S. Food and Drug Administration approved tebentafusp-tebn (Kimmtrak®) in January 2022 as an orphan drug for unresectable or metastatic uveal melanoma in adults, it became the first—and only, at the time of this reference sheet’s publication—drug approved for the indication.

After more than 93% of patients maintained nadir serum asparaginase activity in the therapy’s clinical trials, on June 30, 2021, the U.S. Food and Drug Administration approved asparaginase erwinia chrysanthemi (recombinant)–rywn (Rylaze^TM) for use as a component of a multiagent chemotherapeutic regimen for treatment of acute lymphoblastic leukemia and lymphoblastic lymphoma in adult and pediatric patients who have developed hypersensitivity to E. coli-derived asparaginase.

Bringing the first agent to market for the indication, on August 5, 2022, the U.S. Food and Drug Administration (FDA) approved fam-trastuzumab deruxtecan-nxki (Enhertu®) for patients with unresectable or metastatic HER2-low breast cancer based on results from the DESTINY-Breast04 trial that demonstrated improved progression-free and overall survival. FDA also gave fam-trastuzumab deruxtecan its fourth approval on August 11, 2022, for unresectable or metastatic HER2-activating non-small cell lung cancer (NSCLC).

After clinical trials demonstrated a 25% response rate in patients with multiple myeloma, selinexor (Xpovio^®) received initial, accelerated U.S. Food and Drug Administration approval in 2019.

When Opdualag^TM (nivolumab and relatlimab-rmbw), a fixed-dose combination therapy that consists of two distinct monoclonal antibodies, received FDA approval on March 18, 2022, for the treatment of unresectable or metastatic melanoma for adult and pediatric patients 12 years of age or older, it became the first approved combination therapy that includes two distinct immunotherapy agents in a single infusion. Relatlimab-rmbw is also the first approved lymphocyte activation gene-3–blocking antibody.

After clinical trial results demonstrated a four-month improvement in overall survival compared to best standard care, in March 2022 the U.S. Food and Drug Administration approved lutetium lu 177 vipivotide tetraxetan (Pluvicto^TM) to treat prostate-specific membrane antigen–expressing metastatic castration-resistant prostate cancer.

Based on LOTIS-2 trial results that reported an overall response rate of nearly 50%, in April 2021 the U.S. Food and Drug Administration granted accelerated approval to loncastuximab tesirine-lpyl (Zynlonta^TM) for adults with relapsed or refractory large B-cell lymphoma.

Chronic graft-versus-host disease (GVHD) is a severe adverse reaction after allogeneic hematopoietic cell transplantation that decreases quality of life and is a major cause of death. In July 2021, the U.S. Food and Drug Administration approved belumosudil (Rezurock^TM) as a third-line treatment option for chronic GVHD.

First approved by the U.S. Food and Drug Administration in 2020 for treatment of gastrointestinal stromal tumors (GIST), avapritinib’s (AyvakitTM) approval was extended in 2021 for treatment of advanced systemic mastocytosis (AdvSM). Both approvals are for patients with PDGFR-alpha genetic variants.

An optical imaging agent shown to improve diagnostic accuracy, pafolacianine (Cytalux^TM) was approved on November 29, 2021, for use in adult patients with known or suspected ovarian cancer as adjunct therapy in conjunction with planned intraoperative identification of malignant lesions. Pafolacianine is used in combination with a near-infrared (NIR) fluorescence imaging system that requires specialized training provided by the device manufacturer.

In clinical trials, 24% of patients achieved an objective response rate with tisotumab vedotin-tftv (Tivdak^TM) that lasted a median of 8.3 months, leading to the agent’s U.S. Food and Drug Administration September 2021 approval for use in adults with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy.

Adding to its earlier approvals for use in adults with acute myeloid leukemia (AML), on August 25, 2021, the U.S. Food and Drug Administration (FDA) approved ivosidenib (Tibsovo^®) for adults with previously treated, locally advanced or metastatic cholangiocarcinoma. Cholangiocarcinoma, or cancer of the bile ducts, is a rare cancer, and ivosidenib is the only currently approved agent for patients with an IDH1 variant.

After clinical trials demonstrated a 40% overall response rate with 63% of responses lasting six months or more, on May 21, 2021, the U.S. Food and Drug Administration (FDA) approved amivantamab-vmjw (Rybrevant^TM) for adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion variants, as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy.

After clinical trials demonstrated an overall response rate of 36% and median response duration of 10 months, the U.S. Food and Drug Administration granted sotorasib (Lumakras^TM) accelerated approval on May 28, 2021, for the treatment of adults with KRAS G12C–altered locally advanced or metastatic non-small cell lung cancer (NSCLC), as determined by an FDA-approved test, who have received at least one prior systemic therapy.

A first-of-its-kind antibody-drug conjugate for multiple myeloma, belantamab mafodotin-blmf (Blenrep) received accelerated approval from the U.S. Food and Drug Administration (FDA) in August 2020. The approval was based on clinical trial findings that demonstrated a 31% overall response rate that lasted at least six months in 73% of responders.

Initially marketed in April 2020 for treatment of adults with metastatic triple negative breast cancer, sacituzumab govitecan-hziy (Trodelvy^®) received an additional approval in 2021 for the treatment of patients with locally advanced or metastatic urothelial cancer with prior treatments.

On March 10, 2021, the U.S. Food and Drug Administration approved tivozanib (Fotivda^®), an oral kinase inhibitor, for adult patients with relapsed or refractory advanced renal cell carcinoma (RCC) following two or more prior systemic therapies.

On July 26, 2021, the U.S. Food and Drug Administration (FDA) approved pembrolizumab (Keytruda^®) for high-risk, early-stage, triple-negative breast cancer (TNBC) in combination with chemotherapy as neoadjuvant treatment and continued as a single agent as adjuvant treatment after surgery. 

Pertuzumab, trastuzumab, and hyaluronidase-zzxf subcutaneous injection (Phesgo^TM) was approved by the U.S. Food and Drug Administration (FDA) in June 2020 for patients with advanced HER2-positive breast cancer. The drug components are the same as those in FDA-approved IV version, and study results showed comparable safety and efficacy to the IV counterparts. The new administration route allows eligible patients to bypass infusion centers or even receive the therapy at home.

On July 9, 2021, the U.S. Food and Drug Administration (FDA) approved enfortumab vedotin-ejfv ([EV], Padcev®), a Nectin-4–directed antibody and microtubule inhibitor conjugate, for adult patients with locally advanced or metastatic urothelial cancer who previously received a programmed death receptor-1 (PD-1) or programmed death-ligand (PD-L1) inhibitor and platinum-containing chemotherapy or are ineligible for cisplatin-containing chemotherapy and have previously received one or more prior lines of therapy.

Tepotinib (Tepmetko®) was granted accelerated approval in February 2021 for mesenchymalepithelial transition (MET)-altered metastatic non-small cell lung cancer (NSCLC) based on overall response rate and duration. The drug is still under long-term evaluation and healthcare providers should report all serious adverse events that may be associated to FDA’s MedWatch Reporting System.

On February 12, 2021, the U.S. Food and Drug Administration approved trilaciclib (Cosela^TM), a parenteral inhibitor of cyclin-dependent kinase, to prevent myelosuppression when administered prior to chemotherapy administration. The approval is currently limited to the use of trilaciclib before treatment with platinum- and etoposide-containing regimens and topotecan-containing regimens for treatment of extensive-stage small cell lung cancer.

On December 18, 2020, the U.S. Food and Drug Administration approved relugolix (Orgovyx^TM) as the first oral hormone therapy for use in adult patients with advanced prostate cancer. 

In July 2020, the U.S. Food and Drug Administration approved decitabine and cedazuridine (Inqovi^®) tablets for the treatment of adults with myelodysplastic syndromes. 

Tafasitamab-cxix (Monjuvi^®) received accelerated approval from the U.S. Food and Drug Administration in July 2020 in combination with lenalidomide for adults with relapsed or refractory diffuse large B-cell lymphoma.

When used in combination with fulvestrant, alpelisib (Piqray^®) produced complete or partial responses in 29% of patients with PIK3CA-altered, estrogen receptor-positive advanced breast cancer in clinical trials. The U.S. Food and Drug Administration approved it for use in 2019.

In May 2020, the U.S. Food and Drug Administration gave accelerated approval for selpercatinib (Retevmo^®) to treat RET-altered non-small cell lung cancer or thyroid cancer based on overall response rate and duration of response. Selpercatinib fights cancer by impeding RET protein activity. The determining clinical trial results demonstrated that it reduced tumor size in more than 50% of patients and was associated with fewer adverse reactions than other drugs that block the RET protein.

In June 2020, the U.S. Food and Drug Administration granted accelerated approval to lurbinectedin (Zepzelca^TM) for adults with metastatic small cell lung cancer (SCLC) whose disease has progressed on or after platinum-based chemotherapy. The approval adds a second choice for patients who experience treatment-resistant SCLC progression, who previously had only topotecan as an option.

Zanubrutinib (Brukinsa^TM) received U.S. Food and Drug Administration accelerated approval on November 14, 2019, for the treatment of adult patients with mantle cell lymphoma who have received at least one prior therapy.

Rucaparib (Rubraca^®) has U.S. Food and Drug Administration approval for both maintenance and treatment indications in gynecologic cancers. It originally received accelerated approval in 2016 for the treatment of deleterious, BRCA variant–associated advanced ovarian cancer that has failed two or more chemotherapies. In 2018, it was approved for maintenance therapy of various gynecologic malignancies. Most recently, rucaparib received approval for BRCA-positive metastatic castration-resistant prostate cancer treatment after androgen-directed and chemotherapy.

Enfortumab vedotin-ejfv (Padcev™) was granted accelerated approval in December 2019 for adults with locally advanced or metastatic urothelial cancer who previously received an immune checkpoint inhibitor (PD-1 or PD-L1 inhibitor) and platinum-containing therapy.

Capecitabine (Xeloda^®) was approved by the U.S. Food and Drug Administration (FDA) in 1998 as a nucleoside metabolic inhibitor with antineoplastic activity indicated for adjuvant colon cancer, metastatic colorectal cancer, and metastatic breast cancer.

Daratumumab (Darzalex^®) was originally approved by the U.S. Food and Drug Administration in 2015 with additional indications added since. The most recent new indication was approved in September 2019 for newly diagnosed patients with multiple myeloma who are eligible for autologous stem cell transplantation. In May 2020, daratumumab and hyaluronidase-fihj (Darzalex Faspro™), a subcutaneous (SQ) formulation, was approved.

Tocilizumab was approved in August 2017 for the treatment of chimeric antigen receptor T cell–induced cytokine release syndrome. In March 2020, the U.S. Food and Drug Administration approved a randomized, double-blind, placebo-controlled, phase III clinical trial to assess the safety and efficacy of tocilizumab plus standard of care in patients hospitalized with severe COVID-19 pneumonia.

Approved in 2006 as monotherapy for the treatment of patients with EGFR-expressing metastatic colorectal cancer (mCRC) after disease progression following treatment, panitumumab has been a mainstay metastatic disease for more than a decade. In 2014, it received additional indication as first-line therapy for the treatment of patients with EGFR-expressing mCRC in combination with FOLFOX, but in 2017, use was narrowed to wild-type RAS (not mutated RAS). 

Niraparib was approved in October 2019 for patients with homologous recombination deficiency (HRD)-positive advanced ovarian, fallopian tube, or primary peritoneal cancer. 

Entrectinib was approved by the U.S. Food and Drug Administration in August 2019 as the third tumor-agnostic cancer drug, meaning it targets a specific mutation of the cancer, not the organ of origin. The other two currently approved tumor-agnostic drugs are larotrectinib and pembrolizumab.

Radium 223 dichloride (Xofigo^®) is an alpha particle-emitting radioactive therapeutic agent approved by the U.S. Food and Drug Administration in 2013 for castrate-resistant prostate cancer.

Blinatumomab received accelerated approval from the U.S. Food and Drug Administration (FDA) in 2014 for the treatment of B-cell precursor acute lymphoblastic leukemia. The drug’s unique administration procedures have prompted nurses to evaluate their practice for safety.

Based on the results of the phase III ARAMIS trial that demonstrated significant improvement in metastasis-free survival, the U.S. Food and Drug Administration approved darolutamide under priority review on July 30, 2019. Darolutamide is approved for nonmetastatic, castration-resistant prostate cancer in men receiving concurrent gonadotropin-releasing hormone therapy or who have had bilateral orchiectomy.

Erdafitinib (Balversa™) is the first targeted therapy that the U.S. Food and Drug Administration approved for treatment of metastatic bladder cancer. 

Venetoclax (Venclexta^®) was approved by the U.S. Food and Drug Administration on May 15, 2019, for the treatment of adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) as a single agent or in combination therapy. Previously, it had been approved in late 2018 for use in combination therapy for acute myeloid leukemia (AML) in older adults or those with significant comorbidities.

The U.S. Food and Drug Administration (FDA) first approved atezolizumab (Tecentriq^®) in 2016, but it received additional approvals when used in combination treatments for locally advanced or metastatic triple negative breast cancer (TNBC) and small cell lung cancer (SCLC) in March 2019.

A new product that combines trastuzumab and hyaluronidase (Herceptin Hylecta™) received U.S. Food and Drug Administration approval in February 2019 for the treatment of HER2-overexpressing breast cancer. The approval was based on the results of two randomized trials: HannaH and SafeHER. 

Initially approved in 2018, talazoparib (Talzenna^®) capsules are indicated for the treatment of adult patients with deleterious or suspected deleterious germline breast cancer susceptibility gene HER2-negative locally advanced or metastatic breast cancer.

Cabozantinib (Cabometyx^®) received an additional U.S. Food and Drug Administration (FDA)-approved indication in January 2019 for use in patients with hepatocellular carcinoma (HCC) who have already been treated with sorafenib. It received prior approval for the treatment of renal cell carcinoma in 2017. The research leading to the approval in the HCC setting showed improved overall survival, progression-free survival, and overall response in the cabozantinib treatment arm.

In November 2018, the U.S. Food and Drug Administration (FDA) approved glasdegib (Daurismo™) for use in combination with low-dose cytarabine for treatment of patients with newly diagnosed acute myeloid leukemia who are not eligible for intensive chemotherapy. Data from clinical trials indicated that the regimen is safe for older adults and those with significant comorbidities, such as cardiac disease, poor performance status, or elevated serum creatinine.