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FDA Updates

FDA Updates Highlighting the Latest Cancer Treatments

doi: 10.1097/01.COT.0000553982.06533.85
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Atezolizumab Plus Chemo for Metastatic Non-Squamous NSCLC

oncology; FDA
oncology; FDA:
oncology; FDA

The FDA has accepted the supplemental Biologics License Application (sBLA) for atezolizumab in combination with nab-paclitaxel and carboplatin for first-line treatment of people with metastatic non-squamous non-small cell lung cancer (NSCLC) who do not have EGFR or ALK genomic tumor aberrations. The FDA is expected to make a decision on approval by Sept. 2, 2019.

This sBLA is based on results from the phase III IMpower130 study. This multicenter, open-label, randomized study evaluated the efficacy and safety of atezolizumab in combination with carboplatin and nab-paclitaxel versus chemotherapy (carboplatin and nab-paclitaxel) alone for chemotherapy-naïve patients with stage IV non-squamous NSCLC.

The study enrolled 724 people who were randomized in a 2:1 ratio to receive: atezolizumab plus nab-paclitaxel and carboplatin (Arm A), or nab-paclitaxel and carboplatin (Arm B, control arm).

During the treatment-induction phase, people in Arm A received atezolizumab and carboplatin on day 1 of each 21-day cycle, and nab-paclitaxel on days 1, 8, and 15 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit, whichever occurred first. People in Arm A received atezolizumab during the maintenance treatment phase until loss of clinical benefit was observed.

During this phase, people in Arm B received carboplatin on day 1 and nab-paclitaxel on days 1, 8, and 15 of each 21-day cycle for 4 or 6 cycles or until disease progression, whichever occurred first. People in Arm B received best supportive care during the maintenance treatment phase. Switch maintenance to pemetrexed was also permitted. People who were consented prior to a protocol revision were given the option to crossover following disease progression to receive atezolizumab as monotherapy until further disease progression.

The co-primary endpoints were:

  • PFS as determined by the investigator using RECIST v1.1 in people without EGFR or ALK mutations, assessed in the intention-to-treat wild-type (ITT-WT) population; and
  • OS in the ITT-WT population.

The IMpower130 study met its OS and PFS co-primary endpoints as per the study protocol. The interim analysis showed that atezolizumab plus chemotherapy helped people live significantly longer compared with chemotherapy alone (median OS=18.6 vs. 13.9 months; HR=0.79; 95% CI: 0.64-0.98; p=0.033) in the ITT-WT population. The atezolizumab-based combination also significantly reduced the risk of disease worsening or death (PFS) compared with chemotherapy alone (median PFS=7.0 vs. 5.5 months; HR=0.64; 95% CI: 0.54-0.77; p<0.0001) in the ITT-WT population.

Safety for the atezolizumab plus chemotherapy combination appeared consistent with the known safety profiles of the individual medicines, and no new safety signals were identified with the combination. Grade 3-4 treatment-related adverse events were reported in 73.2 percent of people receiving atezolizumab plus chemotherapy compared to 60.3 percent of people receiving chemotherapy alone.

The FDA recently approved atezolizumab in combination with bevacizumab, paclitaxel, and carboplatin for the initial treatment of people with metastatic non-squamous NSCLC with no EGFR or ALK genomic tumor aberrations.

Atezolizumab is also approved by the FDA to treat people with metastatic NSCLC who have disease progression during or following platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for NSCLC harboring these aberrations prior to receiving atezolizumab.

FDA Advances New Scientific Framework in Oncology Drug Development

The FDA recently issued a guidance, Clinical Trial Endpoints for the Approval of Cancer Drugs and Biologics, that provides recommendations to applicants on endpoints for cancer clinical trials submitted to the FDA to support effectiveness claims in applications. This updated guidance will help advance the efficient development of cancer drugs and biologics. It is a revision of the guidance of the same title published in May 2007 and replaces that prior document.

The new updates made to this guidance expand on the information regarding oncology endpoints and provide updated resources, references, and examples of regulatory approvals. The guidance clarifies how various oncology endpoints can serve different purposes (e.g., clinical endpoint that represents clinical benefit for traditional approval, surrogate endpoint to support traditional approval, surrogate endpoint to support accelerated approval) and provides current thinking on the factors that are considered in making the determination. Other updates include the addition of examples of emerging oncology endpoints and the addition of intermediate clinical endpoints in the discussion of accelerated approval.

“As part of FDA's strategy to continue to encourage the modernization of clinical trials, we're providing new recommendations for drug developers regarding the most effective clinical trial endpoints to help advance the development of products to treat cancer. Over the past several decades, we've seen an evolution in cancer care in how treatment effect is measured, and which endpoints are successful measures of disease activity or clinical benefit to patients,” said FDA Commissioner Scott Gottlieb, MD. “As part of these advances, there's been a robust debate about the use of surrogate endpoints to support both traditional and accelerated approvals. We've engaged patient and health care professional communities to inform our regulatory decision-making around these issues, to ensure we are keeping pace with the science and continuing to encourage development of treatments that offer meaningful results for patients.

“Applying the most efficient clinical trial designs and using meaningful endpoints that measure benefits important to patients is key to our efforts to modernize clinical trial development programs. It helps make research and development more effective and can lower the cost of bringing safe and effective treatments to patients,” he continued. “We're revising guidance for the first time in more than a decade that outlines our thinking on oncology endpoints based on the specific context of use, as well as the advantages and disadvantages of these endpoints in clinical development programs.”

Although the general principles outlined in this guidance should help applicants select endpoints for marketing applications, the FDA recommends that companies meet with the agency before submitting clinical trial protocols intended to support NDA or BLA marketing applications. The FDA will ensure that these meetings include a multidisciplinary FDA team of oncologists, statisticians, clinical pharmacologists, and external expert consultants as needed. Ultimately, marketing approval depends not only on the design of clinical trials, but also clinical trial conduct and the findings from all studies in the drug marketing application.

“We continue to encourage companies to engage with FDA early in the drug development process so that we can work with them to apply modern and efficient trial designs, as well as explore novel endpoints, such as minimal residual disease, which recently formed the basis of approval for [blinatumomab] for a type of leukemia,” Gottlieb stated.

Trastuzumab-Dttb Approved for Breast & Gastric Cancers

The FDA recently approved trastuzumab-dttb, a biosimilar referencing trastuzumab, across all eligible indications, namely adjuvant treatment of HER2-overexpressing breast cancer, metastatic breast cancer, and metastatic gastric cancer or gastroesophageal junction adenocarcinoma in patients who have not received prior treatment for metastatic disease.

Trastuzumab-dttb is the third biosimilar to trastuzumab to receive regulatory approval in the U.S. It was also approved by the European Commission in November 2017, and has since been launched in a growing number of European countries.

Trastuzumab-dttb is indicated for adjuvant treatment of HER2-overexpressing node-positive or node-negative (ER/PR-negative or with one high-risk feature) breast cancer:

  • as part of a treatment regimen containing doxorubicin, cyclophosphamide, and either paclitaxel or docetaxel;
  • with docetaxel and carboplatin; and
  • as a single agent following multi-modality anthracycline-based therapy.

The therapy is also indicated in combination with paclitaxel for the first-line treatment of HER2-overexpressing metastatic breast cancer and as a single agent for treatment of HER2-overexpressing breast cancer in patients who have received one or more chemotherapy regimens for metastatic disease.

Trastuzumab-dttb is approved in combination with cisplatin and capecitabine or 5-fluorouracil for the treatment of patients with HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma, who have not received prior treatment for metastatic disease.

Wolters Kluwer Health, Inc. All rights reserved.
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