Silas Inman

The high durable response rates seen with CAR T-cell therapies have helped fill a high unmet need for patients with relapsed/refractory diffuse large B-cell lymphoma, with questions remaining on the optimal way to use these agents following the FDA approval of 2 therapies in the past year, explained Anas Younes, MD, during a presentation at the <em>36th Annual </em>CFS.

Quick progress was seen with a novel class of agents, chimeric antigen receptor T-cell therapies, in the setting of diffuse large B-cell lymphoma&mdash;a swift jump from early phase clinical trials to FDA-approved products.

Moxetumomab pasudotox has been approved by the FDA for the&nbsp;treatment of adult patients with relapsed or refractory hairy cell leukemia who have received at least 2 prior lines of therapy, including treatment with a purine nucleoside analog.

The review period for a supplemental biologics license application seeking the approval of atezolizumab (Tecentriq) for use in combination with bevacizumab (Avastin), carboplatin, and paclitaxel or the first-line treatment of patients with metastatic nonsquamous non&ndash;small cell lung cancer has been extended by the FDA.

LOXO-292 has been granted a breakthrough therapy designation by the FDA for the treatment of&nbsp;patients with <em>RET</em> fusion&ndash;positive non&ndash;small cell lung cancer or <em>RET</em>-mutant medullary thyroid cancer.

RET will join the ever-expanding actionable driver mutations for non&ndash;small cell lung cancer, according to a presentation by Paul Baas, MD, PhD, at the <em>19th Annual</em> International Lung Cancer Congress.

Combinations with immunotherapy agents have surged ahead with new regimens showing great potential for the treatment of patients with lung cancer, Corey Langer, MD, said during a presentation at the&nbsp;<em>19th Annual </em>International Lung Cancer Congress (ILCC). Knowledge about a growing number of biomarkers are helping to guide treatment decisions with these combination options, he said, but the one standard of care has not yet been determined.

Several novel agents are beginning to show promise for new targets in non&ndash;small cell lung cancer, especially <em>NRG1</em> and <em>LKB1,&nbsp;</em>and could be positioned to join&nbsp;already established standard-of-care therapies.

Several studies presented at the 2018 ASCO Annual Meeting helped further refine and inform treatment strategies for the budding class of CAR T-cell therapies, particularly those directed at CD19, in patients with hematologic malignancies, with a focus on predicting adverse events and optimizing efficacy.

Now that chimeric antigen receptor T-cell therapies have received FDA approval for diffuse large B-cell lymphoma (DLBCL) after moving quickly through early phase clinical trials, research is now exploring ways to&nbsp;shift these agents earlier in the treatment paradigm, according to a discussion at the 2nd Annual Live Medical Crossfire on Hematologic Malignancies.

A strategy of escalating regorafenib from 80 mg to 160 mg per day was superior to starting at a dose of 160 mg per day in patients with refractory metastatic colorectal cancer, according to results from the regorafenib dose optimization study presented at the 2018 World Congress on GI.

According to findings from the&nbsp;IMblaze370 study, atezolizumab alone or in combination with cobimetinib did not demonstrate superior overall survival when compared with regorafenib for the treatment of&nbsp;patients with chemorefractory metastatic colorectal cancer. Findings from the study were presented at the 2018 World Congress on Gastrointestinal Cancer.

According to phase I findings recently published in the<em> New England Journal of Medicine,&nbsp;</em>^&nbsp;the&nbsp;recombinant oncolytic poliovirus PVSRIPO demonstrated&nbsp;a 2- and 3-year overall survival (OS) rate of 21% (95% CI, 11%-33%) for patients with recurrent grade IV malignant glioblastoma.

Overall survival was not improved with the combination of palbociclib and fulvestrant compared with&nbsp;fulvestrant and placebo in the phase III PALOMA-3 trial for patients with HR-positive, HER2-negative metastatic breast cancer who received prior endocrine therapy, according to Pfizer, the developer of the CDK4/6 inhibitor.

The FDA has added PD-L1 status to the&nbsp;labels for pembrolizumab (Keytruda) and atezolizumab (Tecentriq) for existing frontline approvals for platinum-ineligible patients with urothelial carcinoma. The addition was made&nbsp;based on lower overall survival rates with the PD-1/PD-L1 inhibitors compared with platinum-based chemotherapy for patients with PD-L1&ndash;low expressing platinum-eligible urothelial carcinoma.

Osimertinib (Tagrisso) has been approved by The European Commission as a frontline treatment for patients with&nbsp;<em>EGFR</em>-mutant locally-advanced or metastatic non&ndash;small cell lung cancer. The approval is based on data&nbsp;from the phase III FLAURA trial.

Overall survival improved with the combination of atezolizumab, bevacizumab, carboplatin, and paclitaxel versus a treatment regimen of bevacizumab and chemotherapy alone in patients with advanced wild-type nonsquamous non&ndash;small cell lung cancer.

Durable complete remissions were seen in 46% of patients with&nbsp;high-risk diffuse large B-cell lymphoma treated with the CAR T-cell therapy lisocabtagene maraleucel at 6 months.&nbsp;These results come from the updated findings from the phase I, multicenter TRANSCEND trial that were presented at the 2018 ASCO Annual Meeting.

Based on data reported at the 2018 ASCO Annual Meeting, the primary endpoint of the phase III RELEVANCE trial was not met with the combination of rituximab plus lenalidomide showing similar efficacy results compared with rituximab plus chemotherapy in treatment-naive patients with follicular lymphoma. The chemotherapy-free regimen, however, did show a more favorable toxicity profile.&nbsp;

Treatment-naive patients with chronic lymphocytic leukemia achieved high rates of&nbsp;minimal residual disease&ndash;negative status of 77% with peripheral blood testing after 6 cycles from treatment with ibrutinib (Imbruvica) and venetoclax (Venclexta). Additionally, patients in the CAPTIVATE trial, wihch was presented during the 2018 ASCO Annual Meeting, achieved an objective response rate of 100%.

Patients with relapsed/refractory t(11;14) multiple myeloma achieved high rates of responses when venetoclax was added to the combination of carfilzomib and dexamethasone, according to findings from an ongoing phase II study presented during the 2018 ASCO Annual Meeting.

The&nbsp;highly-selective RET&nbsp;inhibitor LOXO-292&nbsp;induced an objective response rate of 77% for patients with&nbsp;RET&nbsp;fusion-positive non&ndash;small cell lung cancer, according to&nbsp;findings from the phase I&nbsp;LIBRETTO-001 study presented at the 2018 ASCO Annual Meeting.

In updated findings from the multicenter phase I CRB-401 study that were presented&nbsp;at the 2018 ASCO Annual Meeting, the anti-BCMA CAR T-cell therapy bb2121 induced a median progression-free survival of 11.8 months and a median duration of response of 10.8 months for patients with relapsed/refractory heavily pretreated multiple myeloma.

The review period for lenvatinib as a first-line treatment for patients with unresectable hepatocellular carcinoma has been extended by the FDA. According to Eisai and Merck, the companies codeveloping the drug, this will allow ample time to review the application.&nbsp;

A supplemental new drug application seeking the approval of cabozantinib for the treatment of patients with previously-treated advanced hepatocellular carcinoma has been accepted by the FDA, according to a statement from Exelixis, the company developing the agent.

Following a planned interim analysis, 2 early-phase clinical trials&nbsp;exploring daratumumab in combination with either a PD-1 inhibitor for multiple myeloma or a PD-L1 inhibitor for non&ndash;small cell lung cancer have been terminated, according to a statement from Genmab, the company codeveloping daratumumab with Janssen.

A new formulation of&nbsp;abiraterone acetate in combination with methylprednisolone has been approved by the FDA&nbsp;as a treatment for men with metastatic castration-resistant prostate cancer, according to Sun Pharma, the company commercializing the treatment.

A drug safety notification warning has been issued by the FDA against the use of the single-agent immune checkpoint inhibitors in the first-line setting for patients with PD-L1&ndash;low expressing platinum-eligible urothelial carcinoma. &nbsp;This follows findings of a decrease in overall survival with pembrolizumab and atezolizumab versus a platinum-based chemotherapy.

In patients with HER2-positive early breast cancer, 6 months of adjuvant treatment with&nbsp;trastuzumab (Herceptin)&nbsp;was noninferior for disease-free survival compared with the standard 12-month schedule, according to findings from the phase III PERSEPHONE trial presented ahead of the 2018 ASCO Annual Meeting.

According to additional analyses from the phase III RESORCE trial published in the<em> Journal of Hepatology,&nbsp;s</em>econd-line regorafenib continued to show antitumor activity regardless of prior dose or time to progression on frontline sorafenib (Nexavar) for patients with unresectable advanced hepatocellular carcinoma.