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Recent FDA News Advancing Treatments in Oncology

doi: 10.1097/01.COT.0000577104.56579.95
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Pembrolizumab Approved for Metastatic Small Cell Lung Cancer

FDA; oncology

FDA; oncology

The FDA granted accelerated approval to pembrolizumab for patients with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy and at least one other prior line of therapy.

Efficacy was investigated in 83 patients with SCLC who had disease progression on or after two or more prior lines of therapy enrolled in one of two multicenter, multi-cohort, non-randomized, open-label trials: KEYNOTE-158 (NCT02628067) Cohort G or KEYNOTE-028 (NCT02054806) Cohort C1. Patients received either pembrolizumab 200 mg intravenously every 3 weeks (n=64) or 10 mg/kg intravenously every 2 weeks (n=19). Treatment continued until documented disease progression, unacceptable toxicity, or a maximum of 24 months.

The main efficacy outcome measures were overall response rate (ORR) and duration of response (modified RECIST v1.1) assessed by blinded independent central review. The ORR was 19 percent (95% CI: 11, 29); the complete response rate was 2 percent. Responses were durable for 6 months or longer in 94 percent, 12 months or longer in 63 percent, and 18 months or longer in 56 percent of the 16 responding patients.

Adverse reactions in patients who received single-agent pembrolizumab for previously treated SCLC were similar to those occurring in patients with other solid tumors who received pembrolizumab. Common adverse reactions reported in at least 20 percent of patients include fatigue, decreased appetite, cough, nausea, and constipation. Pembrolizumab was discontinued for adverse reactions in 9 percent of patients and 25 percent had at least one dose withheld for adverse reactions. Serious adverse reactions occurred in 31 percent. The most frequent (≥2%) serious adverse reactions were pneumonia and pleural effusion.

The recommended pembrolizumab dose for SCLC is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.

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Pembrolizumab Approved for First-Line Treatment of Head & Neck Squamous Cell Carcinoma

The FDA recently approved pembrolizumab for the first-line treatment of patients with metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC).

Pembrolizumab was approved for use in combination with platinum and fluorouracil (FU) for all patients and as a single agent for patients whose tumors express PDL1 (Combined Positive Score [CPS] ≥1) as determined by an FDA-approved test. The FDA also expanded the intended use for the PD-L1 IHC 22C3 pharmDx kit to include use as a companion diagnostic device for selecting patients with HNSCC for treatment with pembrolizumab as a single agent.

Approval was based on KEYNOTE-048 (NCT02358031), a randomized, multicenter, three-arm, open-label, active-controlled trial conducted in 882 patients with metastatic HNSCC who had not previously received systemic therapy for metastatic disease or with recurrent disease who were considered incurable by local therapies.

Patients were randomized (1:1:1) to receive one of the following treatments: pembrolizumab as a single agent; pembrolizumab, carboplatin or cisplatin, and FU; or cetuximab, carboplatin or cisplatin, and FU. Randomization was stratified by tumor PD-L1 expression (Tumor Proportion Score [TPS] ≥50% or <50%), HPV status according to p16 IHC (positive or negative), and ECOG PS (0 vs. 1). PD-L1 expression (TPS and CPS) was determined using the PD-L1 IHC 22C3 pharmDx kit.

Overall survival (OS), sequentially tested in the subgroup of patients with CPS ≥20 HNSCC, the subgroup of patients with CPS ≥1 HNSCC and the overall population, was the major efficacy measure.

The trial demonstrated a statistically significant improvement in OS in the overall population for patients randomized to pembrolizumab plus chemotherapy compared with cetuximab plus chemotherapy at a pre-specified interim analysis. The median OS was 13.0 months for the pembrolizumab plus chemotherapy arm and 10.7 months for the cetuximab plus chemotherapy arm (HR 0.77; 95% CI: 0.63, 0.93; p=0.0067). Results were similar in the CPS ≥20 subgroup (HR 0.69; 95% CI: 0.51, 0.94) and CPS ≥1 subgroup (HR 0.71; 95% CI: 0.57, 0.88).

The trial also demonstrated statistically significant improvements in OS for the subgroups of patients with PD-L1 CPS ≥1 HNSCC and PD-L1 CPS ≥20 HNSCC randomized to pembrolizumab as a single agent compared with cetuximab plus chemotherapy. In the CPS ≥1 subgroup, the median OS was 12.3 months for the pembrolizumab arm and 10.3 months for the cetuximab plus chemotherapy arm (HR 0.78; 95% CI: 0.64, 0.96; p=0.0171). For the CPS ≥20 subgroup, the median OS was 14.9 months for the pembrolizumab arm and 10.7 months for the cetuximab plus chemotherapy arm (HR 0.61; 95% CI: 0.45, 0.83; p=0.0015). At the time of the interim analysis, there was no significant difference in OS between the pembrolizumab as a single-agent arm and the cetuximab plus chemotherapy arm for the overall population.

There were no significant differences in progression-free survival for either pembrolizumab-containing arm compared to the cetuximab plus chemotherapy arm in any population.

The most common adverse reactions reported in ≥20 percent of patients who received pembrolizumab as a single agent in KEYNOTE-048 were fatigue, constipation, and rash. The most common adverse reactions reported in ≥20 percent of patients who received pembrolizumab in combination with chemotherapy in KEYNOTE-048 were nausea, fatigue, constipation, vomiting, mucosal inflammation, diarrhea, decreased appetite, stomatitis, and cough.

The recommended pembrolizumab dose for HNSCC is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.

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FDA Approves Trastuzumab-Anns, a Biosimilar to Trastuzumab

The FDA has approved trastuzumab-anns for all approved indications of trastuzumab for the treatment of HER2-overexpressing adjuvant and metastatic breast cancer and HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma.

Trastuzumab-anns was proven to be highly similar to, and to have no clinically meaningful differences from, trastuzumab based on a comprehensive totality of evidence, which included extensive comparative analytical, pharmacokinetic, and clinical data. At the time of approval, trastuzumab-anns is the only trastuzumab biosimilar to incorporate the evaluation of a single transition in the clinical study, demonstrating similar safety and immunogenicity in patients who were previously on trastuzumab.

Trastuzumab-anns is a biosimilar to trastuzumab, a recombinant DNA-derived humanized monoclonal immunoglobulin G1 kappa antibody. The active ingredient of the biosimilar is a humanized monoclonal antibody that has the same amino acid sequence, structure, and function as trastuzumab. It also has the same pharmaceutical dosage form and same strength after reconstitution as trastuzumab.

In the U.S., trastuzumab-anns is approved for the following:

Adjuvant Breast Cancer

Trastuzumab-anns 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
  • As a single agent following multi-modality anthracycline-based therapy

Select patients for therapy based on an FDA-approved companion diagnostic for a trastuzumab product.

∗High-risk is defined as ER/PR-positive with one of the following features: tumor size >2 cm, age <35 years, or tumor grade 2 or 3.

Metastatic Breast Cancer

Trastuzumab-anns is indicated:

  • In combination with paclitaxel for the first-line treatment of HER2-overexpressing metastatic breast cancer
  • As a single agent for treatment of HER2-overexpressing breast cancer in patients who have received one or more chemotherapy regimens for metastatic disease

Select patients for therapy based on an FDA-approved companion diagnostic for a trastuzumab product.

Metastatic Gastric Cancer

Trastuzumab-anns is indicated, 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.

Select patients for therapy based on an FDA-approved companion diagnostic for a trastuzumab product.

Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
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