【Medical Companion Travel】Summary: In 2021, hematology/oncology was approved for new drugs or new therapies

In 2021, 13 new drugs in the field of hematology/oncology were approved. In addition, there are many other approvals of concern – whether new formulations, expanded indications, or approvals for biosimilars – that expand access in different patient populations across different tumor types.

Last year marked the 50th anniversary of the National Cancer Act of 1971, a landmark piece of legislation dedicated to funding biomedical research, establishing oncology training programs, and establishing a nationwide network of cancer treatment centers. In 2021, 13 new drugs will be approved for hematology/oncology. In addition, there are many other approvals of concern – whether new formulations, expanded indications, or biosimilar approvals – that expand access in different patient populations across different tumor types.

Four new drugs advance the treatment model for patients with non-small cell lung cancer (NSCLC): tepotinib (Tepmetko), amivantamab-vmjw (Rybrevant), sotorasib (Lumakras, Sotolasib), and mobocertinib (Exkivity).

Nivolumab (Opdivo) adds indications, including for first-line treatment of esophageal cancer, gastric cancer, and gastroesophageal junction (GEJ) adenocarcinoma. Notably, nalvulimab has also entered the field of first-line treatment of advanced renal cell carcinoma (RCC), adjuvant therapy for completely resected esophageal cancer or GEJ cancer, and adjuvant treatment of urethral cancer. Meanwhile, fam-trastuzumab deruxtecan-nxki (Enhertu) and pembrolizumab (Keytruda) were approved for HER2-positive stomach cancer and GEJ adenocarcinoma.

Drugs approved for rare cancers include: infigratinib (Truseltiq) and Evonib (Ivosidenib, Tibsovo) for the treatment of cholangiocarcinoma; belzutifan (Welireg) for the treatment of von Hippel-Lindau syndrome; daratumumab, Darzalex) and hyalururonidase-fihj (Darzalex Faspro) are used to treat light amyloidosis; and sirolimus albumin-binding granules (Fyarro) for the treatment of perivascular epithelial cell tumors (PEComa), the first approved treatment for the disease. The approval of Sacituzumab govitecan-hziy (Trodelvy) has given hope to patients with triple-negative breast cancer (TNBC), which was also approved for the treatment of uremia.

At a 3-day special public hearing on the FDA's Advisory Committee on Oncology Drugs (ODAC) in April, not all drugs that received accelerated approval performed well. The committee evaluated the indications for six immune checkpoint inhibitors— including malignancies such as TNBC, metastatic urinary tract carcinoma (mUC), stomach cancer, and hepatocellular carcinoma (HCC), which were approved under the FDA's accelerated approval process but later confirmatory clinical trials failed. The hearing allowed expert comments and patient testimony on 2 indications for atezolizumab (Tecentriq), 3 indications for pambolizumab and 1 indication for navumab.

Ultimately, ODAC voted for the use of pambolizumab and atezizumab for first-line mUC therapy, and atezizumab plus nab-paclitaxel for the treatment of PD-L1-positive metastatic TNBC; and pambolizumab for the treatment of second-line advanced HCC. The FDA panel voted against the use of pambolizumab for the treatment of PD-L-positive stomach and GEJ cancers, and the use of nalvulizumab for the treatment of second-line advanced HCC.

January

Xalkori: Used in relapsed or refractory ALK-positive non-Hodgkin lymphoma (a rare type of non-Hodgkin lymphoma) in children aged 1 year or older and young adults.

· Fam-trastuzumab deruxtecan-nxki (Enhertu): for the treatment of adult patients with locally advanced or metastatic HER2-positive stomach cancer or GEJ adenocarcinoma who have previously received a trastuzumab (Herceptin) regimen.

Dr Yelena Y. Janjigian said: "Trastuzumab deruxtecan has shown efficacy for HER2-positive stomach cancer, and it is important that, on the basis of this efficacy, we continue to try to understand which patients need to continue to receive HER2 suppression and which patients need to switch to other types of treatment because of the loss of HER2. ”

· Daratumumab and hyaluronidase-fihj (Darzalex Faspro): used in combination with bortezomib (Velcade), cyclophosphamide, and dexamethasone (D-VCd; VCd) to treat patients with newly diagnosed mild amyloidosis.

Nivolumab (Opdivo) plus cabozantinib (Cabometyx): for first-line treatment in patients with advanced RCC.

Dr Toni K. Choueiri said: "Navumab plus cabozantinib will be another option for frontline transparent cell RCC, which is not the only combination that has been approved, but I think the combination has some advantages, especially in terms of quality of life data. ”

February

Tepotinib (Tepmetko): For the treatment of metastatic NSCLC adult patients carrying metastatic EXON 14 jump.

Dr Paul K. Paik said: "These patients are usually not involved in critical upfront trials and they need better treatments. The approval of tipotinib is an important step in this regard, and the availability of a well-tolerated and effective oral drug in this patient population is probably the most important aspect of this approval. ”

· Umbralisib (Ukoniq): For the treatment of patients with relapsed or refractory marginal lymphoma (MZL) who have previously received at least 1 anti-CD20 treatment regimen, and patients with relapsed or refractory follicular lymphoma (FL) who have previously received at least 3 systemic treatments.

Dr. Nathan H. Fowler said: "Umbralisib represents a drug in a unique class that is relatively tolerated and has tumor activity in the vast majority of patients. I believe clinicians will use this approach to treat third- or fourth-line FL. This treatment is very effective and has limited toxicity. In addition, it is taken orally, so it is easy to administer. ”

· Lisocabtagene maraleucel (Breyanzi): Used to treat adult patients with certain types of large B-cell lymphoma who do not respond to at least 2 other types of systemic treatments or have relapses. Specifically, the indications include unspecified patients with diffuse large B-cell lymphoma (DLBCL), including patients produced by non-infectious lymphoma, high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, or grade 3B follicular lymphoma.

Cemiplimab-rwlc (Libtayo): For the treatment of patients with locally advanced basal cell carcinoma (BCC) who have been treated with a Hedgehog pathway inhibitor (HHI) or are not suitable for HHI. The drug is also approved for accelerated use in patients with metastatic BCC who have previously received HHI therapy or who are not suitable for HHI.

· Melphalan flufenamide (Pepaxto): Adult patients with relapsed or refractory multiple myeloma treated in combination with dexamethasone who have previously received at least 4 treatments and are refractory to at least one proteasome inhibitor, an immunomodulatory drug, and a CD38-directed monoclonal antibody.

March

Loratinib (Lorlatinib, Lorbrena): Used to treat patients with ALK-positive metastatic NCSLC detected by FDA-approved tests.

· Axicabtagene ciloleucel (Yescarta): Used to treat adult patients with relapsed or refractory follicular lymphoma after systemic therapy of 2nd line or above.

Dr Henry Chi Hang Fung said: "I think this is a breakthrough in CAR-T cell therapy. The first T cell infusion I did in clinical trials was around 1996, and now we're in 2021, a quarter of a century later. We've done a lot of work and there have been a lot of examples of failures, but in the end it worked out and now there are 4 indications. While it is limited to relapsed/refractory diseases, we want to show that it can be used at an earlier time and produce better results, which is just a step forward and we must continue to move forward. ”

· Tivozanib (Fotivda): for the treatment of adult patients with advanced RCC who have relapsed or refractory after having previously received 2 or more systemic therapies.

Pambolizumab: used in combination with platinum and fluoropyrimidine-based chemotherapy for the treatment of patients with metastatic or locally advanced esophageal or gastroesophageal cancer that do not meet surgical resection or definitive chemotherapy.

· Idecabtagene vicleucel (Abecma): For patients with relapsed or refractory multiple myeloma who have previously received 4 or more treatments, including an immunomodulator, a proteasome inhibitor, and an anti-CD38 monoclonal antibody.

· Isatuximab-irfc (Sarclisa): used in combination with carfilzomib (Kyprolis) and dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who have previously received 1 to 3 lines of treatment.

April

Cetuximab (Erbitux): A new bi-weekly dosing regimen (500 mg/m2, 120 minutes intravenously) for the treatment of patients with KRAS wild-type, EGFR-expressed metastatic colorectal cancer or head and neck squamous cell carcinoma.

· Sacituzumab govitecan-hziy (Trodelvy): for patients with locally advanced or metastatic urothelial carcinoma who have previously received platinum-containing chemotherapy and PD-1 or PD-L1 inhibitors. In addition, the drug is routinely approved for the treatment of unresectable patients with locally advanced or metastatic TNBC who have previously received 2 or more systemic treatments, of which at least 1 is used for metastatic disease.

Nivolumab: in combination with a specific type of chemotherapy, for first-line treatment in patients with advanced or metastatic gastric, GEJ, or esophageal adenocarcinoma.

· Dostarlimab-gxly (Jemperli): For patients with recurrent or advanced endometrial cancer who have progressed in or after previous platinum-containing chemotherapy regimens and whose cancer has a mismatch repair defect.

Dr. Bhavana Pothuri said: "Endometrial cancer is the most common gynecological cancer in the United States and this approval is very important for the disease. The incidence of endometrial cancer, as well as the mortality associated with the disease, has been increasing as the proportion of obesity in patients increases and the number of patients with high-risk histological subtypes increases. Therefore, it is very important to have new additional therapies. This is an exciting advance in the treatment of gynecological cancers, especially endometrial cancer. ”

· Loncastuximab tesirine-lpyl (Zynlonta): used to treat adult patients with relapsed or refractory large B-cell lymphoma after 2-line or higher systemic therapy. Indications include unspecified DLBCL, DLBCL caused by low-grade lymphoma, and high-grade B-cell lymphoma.

May

Pabolizumab: in combination with trastuzumab (Herceptin) and fluoropyrimidine and platinum-containing chemotherapy, for the first-line treatment of patients with locally advanced unresectable or metasected HER2-positive gastric or GEJ adenocarcinoma.

Nalvumab: used for adjuvant therapy in patients with residual lesions of esophageal cancer or GEJ cancer who have received complete resection of neoadjuvant chemotherapy.

· Amivantamab-vmjw (Rybrevant): Used to treat adult NSCLC patients carrying exon EGFR 20 insertion mutations.

Dr Melina Elpi Marmarelis said: "Prior to this approval, targeted therapies for NSCLC and patients with EGFR exon 20 alterations had not been approved. A real-world study in France showed that patients with EGFR 20 exon 20 who underwent conventional chemotherapy had as well as those who did not change. Amivantamab is expected to start filling that gap. ”

· Sotorasib (Lumakras): Used to treat adult patients with tumors with KRAS G12C mutations who have undergone at least one previous systemic treatment.

· Infigratinib (Truseltiq): For the treatment of patients with locally advanced or metastatic cholangiocarcinoma who have been previously treated and carry FGFR2 fusion or rearrangement.

June

Avapritinib (Ayvakit): Used to treat adult patients with advanced systemic mast cell disease, including invasive systemic mast cell disease, systemic mastocytosis with hematological tumors, or mast cell leukemia.

· Asparaginase erwinia chrysanthemi (recombinant)-rywn (Rylaze): as a component of multi-drug acute lymphoblastic leukemia and lymphocytic lymphoma, used in the treatment of adults with allergy to E. coli-derived asparaginase and in children 1 month and older.

July

· Enfortumab vedotin-ejfv (Padcev): For patients who have previously received PD-1 or PD-L1 inhibitors and platinum-containing chemotherapy. Indications for the drug are expanded to include adult patients who have received at least one treatment and are not eligible for platinum-containing chemotherapy.

· Daratumumab and hyaluronidase-fihj: used in combination with pomalidomide (Pomalyst) and dexamethasone for the treatment of adult multiple myeloma patients who have received at least first-line therapy, including lenalidomide (Revlimid) and proteasome inhibitors.

· Belumosudil (Rezurock): for patients aged 12 years and older who have previously failed at least 2 systemsic treatments and have chronic graft-versus-host disease (GVHD).

Dr Corey S. Cutler said: "Ibltinib is the first therapy approved to treat this disease, which is a huge step forward for us, but it is not effective for all patients. Many patients who initially respond to ibutinib eventually progress and need a later series of treatments. For these patients, there needs to be more than one treatment option. ”

Pabolizumab: patients with advanced endometrial cancer whose disease progresses after previous systemic therapy in combination with levatinib (Lenvatinib, Lenvima) and are not suitable for therapeutic surgery or radiation therapy with microsatellite instability or mismatch repair defects.

Pambolizumab: combined with chemotherapy before surgery for high-risk, early-stage TNBC patients for a total of 8 cycles, and 9 cycles of pambolizumab monotherapy after surgery.

August

Pabolizumab: in combination with levatinib (lenvatinib, Lenvima) for first-line therapy in patients with advanced RCC.

Dr. Robert J. Motzer said: "Now with these TKI and immunotherapy combinations, you can see that the response rate and the median PFS of almost 24 months show a good therapeutic effect of the combination. ”

· Dostarlimab-gxly: for the treatment of adult patients with recurrent or advanced solid tumors who have progressed during or after treatment and have no satisfactory alternative option for mismatch repair defects.

· Belzutifan (Welireg): Used to treat adult patients with von Hippel-Lindau disease with RCC, central nervous system angioblastoma or pancreatic neuroendocrine tumors that do not require immediate surgery.

Nalvumab: used for adjuvant therapy in patients with urinary urothelial cancer at high risk of recurrence after radical cystectomy, independent of previous neoadjuvant chemotherapy, nodular involvement, or PD-L1 status.

Ivosidenib (Tibsovo): Taken orally, for adult patients with metastatic cholangiocarcinoma with previous treatment, locally advanced stages, or IDH1 mutations.

· Zanubrutinib (Brukinsa): for adult patients with Waldenstr m macroglobulinemia.

September

· Zanubrutinib (Brukinsa): For the treatment of adult patients with relapsed or refractory MZL who have received at least one anti-CD20-based treatment regimen.

· Mobocertinib (Exkivity): Used by FDA-approved assays to detect locally advanced or metastatic NSCLC adult patients with EGFR 20 exon insertion mutations whose disease progresses during or after platinum-based chemotherapy.

Dr Joel Neal said: "This approval represents a huge step forward in building on research and rational design of the drug. As we advance the combination with chemotherapy and between different drugs, we need to look at how to refine these drugs to achieve better central nervous system penetration, better efficacy, and higher response rates. ”

Cabozantinib (Cabometyx): For patients aged 12 years and older with locally advanced or metastatic differentiated thyroid cancer who have progressed after previous vegetant-targeted therapy and are not eligible for radioactive iodine or resistant to radioactive iodine.

· Tisotumab vedotin-tftv (Tivdak): used in adult patients with relapsed or metastatic cervical cancer who have progressed to the disease during or after chemotherapy.

Robert L. Coleman said, "We have very few effective options. The vast majority of cervical cancer patients do not benefit from immunotherapy. In our daily care for patients with advanced metastatic cervical cancer, there is an urgent need for effective and rapidly effective therapies. ”

Ruxolitinib (Jakafi): Used to treat patients with chronic GVHD aged 12 years and older after failure of 1st or 2nd line system therapy.

October

· Brexucabtagene autoleucel (Tecartus): for adult patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia.

Abemaciclib (Verzenio): Endocrine therapy in combination with tamoxifen or aromatase inhibitor forms for adjuvant therapy in patients with early-stage breast cancer with a 20% or more, hormone receptor-positive, HER2-negative, nodule-positive, and high risk of recurrence in FDA-approved tests.

Dr Stephen Johnston said: "The approval represents a paradigm shift as the last new treatment was an aromatase inhibitor from 2002. This represents our progress in understanding primary endocrine resistance, identifying patients who are doomed to relapse despite the best treatments available, and developing interventions to stop these early relapses. This is a very important milestone for a small percentage of patients with high-risk diseases, for whom endocrine therapy alone is not the solution. We can make a big difference for them. ”

Pambolizumab: combined with chemotherapy, with or without bevacizumab (Avastin), for the treatment of patients with persistent, recurrent, or metastatic cervical cancer with a positive score of at least 1 for tumor expression determined by FDA-approved tests.

Atezolizumab (Tecentriq): Used to adjuvant therapy in patients with stage II to IIIA NSCLC with tumor PD-L1 expression of at least 1%.

· Asciminib (Scemblix): For patients in the chronic phase of Philadelphia chromosome-positive chronic myeloid leukemia (CML) who have previously been treated with 2 or more tyrosine kinase inhibitors.

Dr Michael J. Mauro said: "Asciminib represents a huge step forward in CML. This is a different type of ABL inhibitor; it works through different mechanisms. It's not just another drug that targets the same region of this abnormal enzyme or kinase. It is novel, highly effective, very safe and unique. ”

November

Pambolizumab: for adjuvant treatment of patients with RCC with a medium or high risk of recurrence after nephrectomy alone or resecting metastatic lesions.

Sirolimus albumin-binding granules (Fyarro): an injectable suspension for adult patients with locally advanced unresectable or metastatic malignant PEComa.

· Pafolacianine (Cytalux): an optical imaging agent used as an adjunct to identify malignant lesions between surgeries in adult patients with ovarian cancer.

December

Darrituliumab and hyaluronidase-fihj plus carafezzomib (Kyprolis) plus dexamethasone: for adult patients with relapsed or refractory multiple myeloma who have previously received 1 to 3-line therapy.

Rituximab (Rituximab): Used in combination with chemotherapy for the treatment of children aged 6 months to 18 years, previously untreated, advanced CD20-positive DLBCL, Burkitt lymphoma, Burkitt lymphoma, Burkitt-like lymphoma, or mature B-cell acute leukemia.

Pambolizumab: for adjuvant therapy in patients with IIB or IIC stage melanoma 12 years of age or older after complete resection.

Dr Jason Luke said: "When we started this trial, there were some naysayers who said that patients in IIB and IIC phases were too low risk to be treated in clinical trials. I think these results underscore that these patients do have a high risk of rapid and distant metastatic recurrence. Treatment with pambolizumab can greatly improve the condition. I think this treatment should be available to all patients with IIB and IIC stage disease, and we should not default to non-mode melanoma as low risk; in fact, it is high risk and these patients should have the opportunity to receive treatment. ”

Abatacept (Orencia): for the prevention of acute GVHD, in combination with calcitoninase inhibitors and methotrexate, for adults and children aged 2 years and older who receive hematopoietic stem cell transplantation from a matched or 1 allele mismatched non-kin donor.