Priority Review in Squamous NSCLC, European Recommendations, and More

Today-

A priority review in non—small cell lung cancer, European recommendations in a number of hematologic malignancies, breast cancer, and melanoma, and promising findings in a triple-negative breast cancer trial.

Welcome to OncLive News Network! I'm Gina Columbus.

The FDA has granted a priority review designation to a supplemental biologics license application for first-line pembrolizumab combined with carboplatin/paclitaxel or nab-paclitaxel for the treatment of patients with metastatic squamous non—small cell lung cancer, regardless of PD-L1 expression.

The application is based on results from the phase III KEYNOTE-407 trial, in which combining pembrolizumab with chemotherapy reduced the risk of death by 36% versus chemotherapy alone in patients with metastatic squamous NSCLC. The median overall survival was 15.9 months with pembrolizumab versus 11.3 months with chemotherapy alone. The OS benefit was observed across subgroups.

Moreover, the median PFS was 6.4 months with the PD-1 inhibitor versus 4.8 months with chemotherapy alone. There was also a correlation between an increase in PD-L1 level and a greater magnitude of benefit.

The objective response rate in the pembrolizumab arm was 57.9%, with a complete response rate of 1.4% and a partial response rate of 56.5%. This compared with an ORR of 38.4% in the control arm, with a CR rate of 2.1% and a PR rate of 36.3%. The duration of response was 7.7 months versus 4.8 months in the pembrolizumab versus placebo arms, respectively.

Under the Prescription Drug User Fee Act, the FDA is scheduled to make its final decision on the application by October 30, 2018.

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The European Medicines Agency’s Committee for Medicinal Products for Human Use has recommended approval of the chimeric antigen receptor T-cell therapy axicabtagene ciloleucel as a treatment for adult patients with relapsed/refractory diffuse large B-cell lymphoma or primary mediastinal large B-cell lymphoma, following at least 2 lines of systemic therapy.

The recommendation is based on findings from the single-arm phase II ZUMA-1 trial, which showed that axi-cel had an objective response rate of 82% and a complete remission rate of 54%. After 8.7 months of follow-up, 39% of patients remained in CR.

Moreover, the median duration of response in those with a CR was not reached at the time of the assessment. The FDA label for the medication in the United States lists the ORR as 72% and the CR rate as 51%.

The European Commission will now review the CHMP recommendation and make a final decision on whether to approve axicabtagene ciloleucel for use in the European Union.

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A second chimeric antigen receptor T-cell therapy, tisagenlecleucel, has been recommended for approval by the European Medicines Agency’s Committee for Medicinal Products for Human Use. The indication would be for either adult patients with diffuse large B-cell lymphoma that is relapsed or refractory after 2 or more lines of systemic therapy, or patients up to 25 years of age with B-cell acute lymphoblastic leukemia that is refractory, in relapse posttransplant, or in second or later relapse

The DLBCL recommendation was based on data from the phase II JULIET study. At a median follow-up of 14.1 months, tisagenlecleucel achieved an objective response rate of 52% in adult patients with relapsed/refractory disease. The ORR included a complete response rate of 40% and a partial response rate of 12%. This response was durable, as the duration of response had not been reached at data cutoff.

These response rates were consistent across all subgroups, including patients receiving prior allogeneic stem cell transplantation, and in patients having double-hit lymphoma. Additionally, the 12-month relapse-free survival rate in patients with a CR was 78.5% and the 12-month RFS rate in all responders was 65%. There were no patients who proceeded to transplant while in response.

The ALL recommendation was based on data from the phase II ELIANA trial, which demonstrated that at a median follow-up of 13.1 months, tisagenlecleucel induced an ORR of 81% in children and young adults with relapsed/refractory B-cell ALL.

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In breast cancer, the European Medicines Agency’s Committee for Medicinal Products for Human Use has recommended approval of neratinib for the extended adjuvant treatment of adult patients with early stage hormone receptor—positive, HER2-overexpressed/amplified disease following postoperative trastuzumab.

The agency reviewed results from the phase III ExteNET trial and the phase II CONTROL trial. The primary analysis of the ExteNET trial showed that the invasive disease-free survival rate at 2 years was 94.2% with neratinib versus 91.9% with placebo.

The results suggested that the benefit may vary based on hormone receptor status. An exploratory subgroup analysis indicated that neratinib lowered the risk of recurrence by 51% in HR—positive patients versus 7% in HR–negative patients.

Diarrhea was the primary safety concern associated with neratinib, as 95% of patients in the ExteNET trial who received it experienced the adverse event, including grade 3 cases in 40% of patients. However, additional data show that antidiarrheal prophylaxis can control the occurrence and severity of diarrhea among patients receiving neratinib.

In the United States, the FDA approved neratinib in July 2017 for the extended adjuvant treatment of patients with early stage, HER2-positive breast cancer following adjuvant trastuzumab.

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The European Medicines Agency’s Committee for Medicinal Products for Human Use has recommended approval of CPX-351, a fixed-combination of daunorubicin and cytarabine, for adult patients with newly diagnosed therapy-related acute myeloid leukemia or AML with myelodysplasia-related changes.

The positive opinion is based on findings from 5 studies, including a pivotal phase III trial. The phase III study compared CPX-351 with traditional cytarabine and daunorubicin for patients with newly diagnosed t-AML or AML-MRC. In the study, the median overall survival was 9.56 months with CPX-351 versus 5.95 months with 7+3, representing a 31% reduction in the risk of death.

The complete response or CR with incomplete platelet or neutrophil recovery rate was 47.7% versus 33.3% for CPX-351 and 7+3, respectively. For CR alone, the rates were 37.3% for CPX-351 and 25.6% for 7+3.

At 12 months, the OS rate was 41.5% in the CPX-351 arm versus 27.6% with 7+3. At 24 months, 31.1% of patients enrolled in CPX-351 remained alive compared with 12.3% with 7+3. The median event-free survival was 2.53 months CPX-351 versus 1.31 months with 7+3.

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In melanoma, the European Medicines Agency’s Committee for Medicinal Products for Human Use has recommended approval of nivolumab as an adjuvant therapy for adult patients with completely resected disease with lymph node involvement or metastatic disease.

The recommendation is based on findings from the phase III CheckMate-238 trial, in which the recurrence-free survival rate at 18 months with nivolumab was 66.4% versus 52.7% for ipilimumab in patients with stage IIIB/C or IV melanoma. There was a 35% reduction in the risk of recurrence or death with the PD-1 inhibitor versus the CTLA-4 inhibitor.

Moreover, the median RFS had not yet been reached in either arm of the trial, and the 12-month RFS rate with nivolumab was 70.5% versus 60.8% in the ipilimumab group. The median distant metastasis-free survival was not reached in either treatment group, with fewer events noted in the nivolumab arm.

Improvements in RFS were seen regardless of tumor stage. In those with stage IIIB/C, the 12-month RFS rates were 72.3% versus 61.6%, for nivolumab and ipilimumab, respectively. In those with stage IV disease, the 12-month RFS rate was 63.0% with nivolumab versus 57.5% with ipilimumab.

The FDA approved nivolumab in December 2017 as an adjuvant treatment for patients with completely resected melanoma with lymph node involvement or metastatic disease.

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Topline results from the phase III Impassion130 trial showed that frontline treatment with atezolizumab plus nab-paclitaxel significantly reduced the risk of disease progression or death versus nab-paclitaxel alone in patients with metastatic or unresectable locally advanced triple-negative breast cancer.

Genentech (Roche), the manufacturer of atezolizumab, reported that no new safety signals emerged with the combination and adverse events were consistent with previous single-agent use of the drugs.

The phase III IMpassion130 study followed a phase Ib study of atezolizumab plus nab-paclitaxel, which showed that the combination had a confirmed ORR of 66.7% as a frontline treatment for patients with metastatic TNBC.

The study explored atezolizumab plus nab-paclitaxel across several lines of treatment regardless of PD-L1 status for patients with metastatic TNBC. In the second-line setting, the confirmed ORR was 25% and in the third-line and beyond the ORR was 28.6%. Across the full trial, the ORR was 41.7%.

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This week, we sat down with Dr Mohammad Jahanzeb of Sylvester Comprehensive Cancer Center to discuss factors to consider for adjuvant therapy in breast cancer.

That’s all for today.

Thank you for watching OncLive News Network! I'm Gina Columbus.