ASCO 2015 Highlights

On March 5, 2021, the FDA approved a new indication for axicabtagene ciloleucel (Yescarta; Kite Pharma), a chimeric antigen receptor (CAR) T-cell therapy, for the treatment of patients with relapsed or refractory follicular lymphoma (FL) who have received ≥2 lines of systemic therapy. The FDA granted this indication a priority review as well as breakthrough therapy and orphan drug designations.

On March 3, 2021, the FDA approved a new indication for lorlatinib (Lorbrena; Pfizer), a third-generation ALK inhibitor, for the first-line treatment of patients with non–small-cell lung cancer (NSCLC) and ALK mutation.

On February 9, 2021, the FDA approved a new indication for cemiplimab-rwlc (Libtayo; Regeneron/sanofi-aventis) for the treatment of locally advanced or metastatic basal-cell carcinoma (BCC) in patients who had received or are ineligible to receive a hedgehog inhibitor. The FDA granted cemiplimab a priority review and accelerated its approval for this indication.

Sacituzumab govitecan (Trodelvy) led to increased response rates and improved progression-free survival (PFS) compared with chemotherapy in heavily pretreated patients with metastatic triple-negative breast cancer (TNBC) and stable brain metastases, according to a subgroup analysis of the phase 3 ASCENT clinical trial. The drug did not lead to improved overall survival (OS) in patients with stable brain metastases. These results were presented at the 2020 San Antonio Breast Cancer Symposium (SABCS).

Pembrolizumab (Keytruda) plus chemotherapy improved progression-free survival (PFS) compared with chemotherapy alone as first-line treatment of metastatic triple-negative breast cancer (TNBC), according to the results of KEYNOTE-355. Improvement in PFS with the addition of pembrolizumab to chemotherapy was more robust in patients with TNBC and PD-L1 expression. These results from KEYNOTE-355 were presented at the 2020 San Antonio Breast Cancer Symposium (SABCS) and add to a growing body of evidence supporting the first-line use of pembrolizumab plus chemotherapy combinations for TNBC.

A small-molecule CD73 inhibitor (AB680) induced a 41% overall response rate (ORR) when combined with chemotherapy (with nab-paclitaxel and gemcitabine), plus the novel PD-1 inhibitor zimberelimab, as a first-line treatment for patients with metastatic pancreatic ductal adenocarcinoma, according to results of the dose-escalation portion of a phase 1/1b study known as ARC-8.

The HER2-targeted bispecific investigational antibody zanidatamab, either as monotherapy or in combination with chemotherapy, has shown promising antitumor activity in an ongoing phase 1 study of patients with HER2-expressing biliary tract cancer or gastroesophageal adenocarcinoma, reported Funda Meric-Bernstam, MD, Chair, Department of Investigational Cancer Therapeutics, M.D. Anderson Cancer Center, Houston, TX, at the 2021 ASCO Gastrointestinal Cancers Symposium.

Final results from the phase 3 clinical trial ClarIDHy showed that ivosidenib (Tibsovo), a first-in-class oral inhibitor of isocitrate dehydrogenase 1 (IDH1) mutation, prolonged the median overall survival (OS) in patients with previously treated advanced cholangiocarcinoma (CCA) and IDH1 mutation. Although this improvement did not reach statistical significance, after adjusting for crossovers from the placebo to the ivosidenib group, the difference in median OS was statistically significant.

Belzutifan, an oral, novel hypoxia-inducible factor (HIF)-2α inhibitor, showed encouraging activity as a single agent in heavily pretreated patients with advanced clear-cell renal-cell carcinoma (RCC) associated with von Hippel-Lindau (VHL) disease, as well as impressive tumor shrinkage when used in combination with cabozantinib (Cabometyx) in separate studies presented at the 2021 ASCO Genitourinary Cancers Symposium.

Cabazitaxel (Jevtana) is approved as third-line therapy for patients with metastatic castration-resistant prostate cancer (CRPC) after treatment with docetaxel and an androgen receptor inhibitor. A new phase 2 clinical trial shows that the radionuclide therapy that targets the prostate-specific membrane antigen (PSMA), ¹⁷⁷Lu-PSMA-617, reduced the risk for disease progression or death by 37% compared with cabazitaxel in men with previously treated metastatic CRPC. Moreover, the TheraP study showed that patients who received ¹⁷⁷Lu-PSMA-617 had fewer side effects and improved quality of life compared with patients who received cabazitaxel.