Pembrolizumab with Chemotherapy Approved for Unresectable Advanced or Metastatic Malignant Pleural Mesothelioma
The US Food and Drug Administration has approved pembrolizumab with chemotherapy as a first-line treatment of unresectable advanced or metastatic malignant pleural mesothelioma (MPM). The decision was based on the findings from the KEYNOTE-483 trial in patients with unresectable advanced or metastatic MPM and no prior systemic therapy for advanced/metastatic disease.1
The trial randomized patients into groups that received either pembrolizumab for up to 2 years in combination with pemetrexed and platinum-based chemotherapy for up to six cycles or pemetrexed and platinum-based chemotherapy for up to six cycles.1 The findings demonstrated a significant improvement in overall survival (OS) for patients who were treated with both pembrolizumab and chemotherapy compared to those who only received chemotherapy.1
Median OS was 17 months (95% CI: 14.4, 21.3) versus 16 months (95% CI: 13.1, 18.2) (hazard ratio [HR] 0.79 [95% CI: 0.64, 0.98]; p=0.0162), and median progression-free survival (PFS) was 7.1 months (95% CI: 6.9, 8.1) versus 7.1 months (95% CI: 6.8, 7.7) in pembrolizumab plus chemotherapy and the chemotherapy-alone arm (HR 0.80 [95% CI: 0.65, 0.99]; p = 0.0194).1 The confirmed objective response rate (ORR) was 52% (95% CI: 45.5, 59.0) in the pembrolizumab plus chemotherapy arm and 29% (95% CI: 23.0, 35.4) in the chemotherapy-alone arm; the median duration of response (DoR) was 6.9 months (95% CI: 5.8, 8.3) and 6.8 months (95% CI: 5.5, 8.5), respectively.1
Amivantamab-vmjw Receives FDA Approval for NSCLC With EGFR Exon 19 Deletions Or L858R Mutations
Amivantamab-vmjw with carboplatin and pemetrexed has been approved for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR exon 19 deletions or exon 21 L858R substitution mutations whose disease has progressed on or after treatment with an EGFR TKI.2 The decision was based on the results of the MARIPOSA-2 trial in patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations who had disease progression on or after receiving osimertinib.2
In the randomized trial, patients either received amivantamab-vmjw with carboplatin and pemetrexed (amivantamab plus CP), carboplatin and pemetrexed (CP), or amivantamab-vmjw as part of another combination regimen. PFS for the comparison between amivantamab plus CP and CP was the major efficacy outcome as assessed by blinded independent central review (BICR).2 The key secondary outcomes were OS and overall response rate (ORR) per BICR.
Median PFS was 6 months (95% CI: 5.6, 8.4) in the amivantamab plus CP arm and 4 months (95% CI: 4.0, 4.4) in the CP arm (HR 0.48 [95% CI: 0.36, 0.64], p-value < 0.0001).2 The confirmed ORR was 53% (95% CI: 44, 62) in the amivantamab plus CP arm and 29% (95% CI: 23, 35) in the CP arm (p-value < 0.0001).2
FDA Greenlights Osimertinib for Locally Advanced, Unresectable NSCLC
Following results from the double-blind, randomized, placebo-controlled LAURA trial, the FDA has approved osimertinib for patients with locally advanced, unresectable stage III NSCLC, whose disease didn’t improve during or after platinum-based chemoradiation therapy and whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations.3
The LAURA trial randomized patients to receive either 80 mg of osimertinib orally once daily or placebo until there was disease progression or unacceptable toxicity.3 The findings found that osimertinib showed a statistically significant improvement in PFS compared to placebo with an HR of 0.16 (95% CI: 0.10, 0.24; p-value < 0.001).3 The median PFS was 39 months (95% CI: 31.5, not estimable [NE]) in the osimertinib arm and 6 months (95% CI: 3.7, 7.4) in the placebo arm.3
Nivolumab Approved as Neoadjuvant Treatment for Resectable NSCLC
The FDA has approved nivolumab with platinum-doublet chemotherapy as neoadjuvant treatment, followed by single-agent nivolumab after surgery as adjuvant treatment, for adults with resectable NSCLC and no known EGFR mutations or ALK rearrangements.4 The approval follows findings from the CHECKMATE-77T trial.
The trial randomized patients to receive nivolumab or placebo with platinum-based chemotherapy every 3 weeks for up to 4 cycles, which was followed by either continued single-agent nivolumab or placebo every 4 weeks for up to 13 cycles.4 The major efficacy outcome was event-free survival (EFS); the median EFS was not reached (95% CI: 28.9, NE) in the nivolumab arm and 18 months (95% CI: 13.6, 28.1) in the chemotherapy arm (HR 0.58 [95% CI: 0.43, 0.78]; p-value 0.00025).4
The adverse reactions were similar to other clinical trials assessing nivolumab with chemotherapy, and 5% of those who received neoadjuvant nivolumab were unable to undergo surgery due to adverse reactions compared with 4% in the placebo arm.4 Additionally, 4.5% who received neoadjuvant treatment and surgery in the nivolumab arm had delays in surgery due to adverse reactions compared with 3.9% in the placebo arm.4
Resources
- 1. FDA approves pembrolizumab with chemotherapy for unresectable advanced or metastatic malignant pleural mesothelioma
- 2. FDA approves amivantamab-vmjw with carboplatin and pemetrexed for non-small cell lung cancer with EGFR exon 19 deletions or L858R mutations
- 3. FDA approves osimertinib for locally advanced, unresectable (stage III) non-small cell lung cancer following chemoradiation therapy
- 4. FDA approves neoadjuvant/adjuvant nivolumab for resectable non-small cell lung cancer
