Targeted Therapies and Immunotherapies for Cancer: 2021 Year in Review

In 2021, FDA issued 51 new approvals/indications for targeted therapies and immunotherapies, 21 of which require a genetic biomarker as part of the indication. 

The vast majority of these biomarker-directed approvals were for solid tumors (18/21), with non-small cell lung cancer (NSCLC) leading the way with 7.  Many approvals were for settings that already had other biomarker-directed options approved prior to 2021, such as the tepotinib approval for NSCLC which is a second option for MET exon 14 skipping (capmatinib was approved in 2020). 

On the other hand, a few key approvals in NSCLC expanded the alterations with targeted options:

• first drug approval for KRAS (sotorasib)

• first drug approvals for EGFR exon 21 insertion mutations (amivantamab, mobocertinib) 

Here is a rundown of all genetic biomarker-directed approvals from 2021:

Januaury

crizotinib for pediatric patients 1 year of age and older and young adults with relapsed or refractory, systemic anaplastic large cell lymphoma (ALCL) that is ALK-positive.

fam-trastuzumab deruxtecan for adult patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen.

February

tepotinib for adult patients with metastatic non-small cell lung cancer (NSCLC) harboring mesenchymal-epithelial transition (MET) exon 14 skipping alterations.

cemiplimab for the first-line treatment of patients with advanced non-small cell lung cancer (NSCLC) (locally advanced who are not candidates for surgical resection or definitive chemoradiation or metastatic) whose tumors have high PD-L1 expression (Tumor Proportion Score [TPS] > 50%) as determined by an FDA-approved test, with no EGFR, ALK or ROS1 aberrations.

March

lorlatinib for patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK)-positive, as detected by an FDA-approved test. lorlatinib was already approved for subsequent-line treatment.  This update extends it to first-line treatment

April

sacituzumab govitecan for patients with unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) who have received two or more prior systemic therapies, at least one of them for metastatic disease.

dostarlimab for adult patients with mismatch repair deficient (dMMR) recurrent or advanced endometrial cancer, as determined by an FDA-approved test, that has progressed on or following a prior  platinum-containing regimen.

May

pembrolizumab + trastuzumab + fluoropyrimidine + platinum chemotherapy for the first-line treatment of patients with locally advanced unresectable or metastatic HER2 positive gastric or gastroesophageal junction (GEJ) adenocarcinoma.

amivantamab for adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations, as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy.

sotorasib for adult patients with KRAS G12C ‑mutated 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.

infigratinib for adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement as detected by an FDA-approved test.

July

pembrolizumab + chemotherapy for high-risk, early-stage, triple-negative breast cancer (TNBC) as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery.

August

belzutifan for adult patients with von Hippel-Lindau (VHL) disease who require therapy for associated renal cell carcinoma (RCC), central nervous system (CNS) hemangioblastomas, or pancreatic neuroendocrine tumors (pNET), not requiring immediate surgery.

dostarlimab for adult patients with mismatch repair deficient (dMMR) recurrent or advanced solid tumors, as determined by an FDA-approved test, that have progressed on or following prior treatment and who have no satisfactory alternative treatment options.

ivosidenib for adult patients with previously treated, locally advanced or metastatic cholangiocarcinoma with an isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test.

September

mobocertinib for adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations, as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy.

October

abemaciclib + endocrine therapy for adjuvant treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, node-positive, early breast cancer at high risk of recurrence and a Ki-67 score ≥20%, as determined by an FDA approved test.

pembrolizumab + chemotherapy +/- bevacizumab for patients with persistent, recurrent or metastatic cervical cancer whose tumors express PD-L1 (CPS ≥1), as determined by an FDA-approved test.

atezolizumab for adjuvant treatment following resection and platinum-based chemotherapy in patients with stage II to IIIA non-small cell lung cancer (NSCLC) whose tumors have PD-L1 expression on ≥ 1% of tumor cells, as determined by an FDA-approved test.

asciminib for patients with Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase (CP), previously treated with two or more tyrosine kinase inhibitors (TKIs), and for adult patients with Ph+ CML in CP with the T315I mutation.

December

rituximab + chemotherapy for pediatric patients (≥6 months to <18 years) with previously untreated, advanced stage, CD20-positive diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma (BL), Burkitt-like lymphoma (BLL), or mature B-cell acute leukemia (B-AL).