FDA Approvals Expand Treatment Options for Breast and Lung Cancers

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Ribociclib for Early Breast Cancer

The FDA has approved ribociclib, in combination with an aromatase inhibitor, for the adjuvant treatment of hormone receptor-positive (HR-positive), human epidermal growth factor receptor 2-negative (HER2-negative) early breast cancer. This approval targets patients with stage II and III cancers who are at high risk of recurrence, marking a significant step forward for individuals in these earlier stages of disease. Additionally, the FDA has approved ribociclib plus letrozole for the same indication.

The efficacy of ribociclib was demonstrated through the NATALEE trial, a randomized, open-label, multicenter study involving 5,101 adults with early HR-positive, HER2-negative breast cancer. The trial recruited patients with lymph node involvement or other risk factors such as large tumor size and high-grade tumors.

Participants were randomized into two groups: those receiving ribociclib combined with a non-steroidal aromatase inhibitor (NSAI) and those receiving NSAI alone. The main measure of success in the trial was invasive disease-free survival (iDFS), defined as the time from randomization to the first event of invasive breast cancer recurrence or death from any cause.

At 36 months, iDFS was significantly better in the ribociclib + NSAI group compared to the NSAI-alone group, with iDFS rates of 90.7% and 87.6%, respectively. The hazard ratio (HR) of 0.749 indicates that ribociclib reduced the risk of recurrence or death by approximately 25% compared to the control arm.

The safety profile of ribociclib was consistent with prior data, and the recommended dose is 400 mg taken orally for 21 consecutive days in a 28-day treatment cycle. This regimen is expected to provide an effective and manageable option for patients undergoing adjuvant therapy.

Pembrolizumab for Advanced Malignant Pleural Mesothelioma

The FDA also approved pembrolizumab in combination with pemetrexed and platinum-based chemotherapy as the first-line treatment for patients with unresectable advanced or metastatic malignant pleural mesothelioma (MPM). This approval marks an important step in the treatment landscape for MPM, which has long had limited therapeutic options.

The approval of pembrolizumab was based on results from the KEYNOTE-483 trial, which enrolled 440 patients with unresectable advanced or metastatic MPM who had not received prior systemic therapy. Patients were divided into two groups: one receiving pembrolizumab with pemetrexed and platinum chemotherapy, and the other receiving chemotherapy alone.

The results showed a clear survival benefit for the pembrolizumab group, with a median over survival of 17.3 months compared to 16.1 months in the chemotherapy-only group, corresponding to a hazard ratio of 0.79. This suggests that patients treated with pembrolizumab had a 21% lower risk of death compared to those on chemotherapy alone. Moreover, patients receiving pembrolizumab showed a significantly higher objective response rate of 52%, compared to 29% in the chemotherapy-only group, indicating a stronger tumor response to the combination therapy.

The adverse effects observed with pembrolizumab in the trial were consistent with those previously reported in other studies. The approved dosage of pembrolizumab is either 200 mg every three weeks or 400 mg every six weeks, with treatment continuing for up to two years or until disease progression.

Amivantamab With Carboplatin and Pemetrexed for EGFR Mutated NSCLC

The FDA additionally approved amivantamab-vmjw combined with carboplatin and pemetrexed for adults with locally advanced or metastatic non-small cell lung cancer (NSCLC) that harbors EGFR exon 19 deletions or exon 21 L858R mutations. This treatment is intended for patients whose disease progressed after EGFR tyrosine kinase inhibitor (TKI) therapy.

Approval was based on the MARIPOSA-2 trial, which included 657 patients. The study showed that the amivantamab combination significantly improved progression-free survival (PFS) compared to carboplatin and pemetrexed alone. Patients receiving amivantamab + CP had a median PFS of 6.3 months, compared to 4.2 months for the CP group, with a hazard ratio of 0.48. The overall response rate was also higher in the amivantamab group (53% vs. 29%).

Common side effects included rash, infusion reactions, fatigue, nausea, and musculoskeletal pain. This approval provides a new option for patients with advanced NSCLC, offering improved outcomes for those with limited alternatives.

Osimertinib for Locally Advanced Unresectable NSCLC

Finally, the FDA approved osimertinib for adults with locally advanced, unresectable (stage III) non-small cell lung cancer whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations. This approval targets patients whose cancer has not progressed during or after platinum-based chemoradiation therapy.

The approval is based on the LAURA trial, a randomized, placebo-controlled study of 216 patients. The study demonstrated a significant improvement in progression-free survival (PFS) for those receiving osimertinib. The median PFS was 39.1 months for the osimertinib group, compared to just 5.6 months for placebo, with a hazard ratio of 0.16. While overall survival data is still immature, no negative trends were noted. Common side effects included lymphopenia, interstitial lung disease, neutropenia, rash, diarrhea, and musculoskeletal pain.

With further research and clinical trials ongoing, these approvals are part of a larger effort to enhance survival and quality of life for cancer patients, showcasing the continuous progress in oncology therapies.

References

1. FDA approves Kisqali with an aromatase inhibitor and Kisqali Femara Co-Pack for early high-risk breast cancer,” U.S. Food And Drug Administration, Sep. 17, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-kisqali-aromatase-inhibitor-and-kisqali-femara-co-pack-early-high-risk-breast-cancer
2. D. J. Slamon et al., “Ribociclib and endocrine therapy as adjuvant treatment in patients with HR+/HER2- early breast cancer: Primary results from the phase III NATALEE trial.,” Journal of Clinical Oncology, vol. 41, no. 17_suppl, p. LBA500, Jun. 2023, doi: 10.1200/jco.2023.41.17_suppl.lba500.
3. FDA approves pembrolizumab with chemotherapy for unresectable advanced or metastatic malignant pleural mesothelioma,” U.S. Food And Drug Administration, Sep. 17, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-chemotherapy-unresectable-advanced-or-metastatic-malignant-pleural
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5. FDA approves amivantamab-vmjw with carboplatin and pemetrexed for non-small cell lung cancer with EGFR exon 19 deletions or L858R mutations,” U.S. Food And Drug Administration, Sep. 19, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-amivantamab-vmjw-carboplatin-and-pemetrexed-non-small-cell-lung-cancer-egfr-exon-19
6. A. Passaro et al., “Amivantamab plus chemotherapy with and without lazertinib in EGFR-mutant advanced NSCLC after disease progression on osimertinib: primary results from the phase III MARIPOSA-2 study,” Annals of Oncology, vol. 35, no. 1, pp. 77–90, Oct. 2023, doi: 10.1016/j.annonc.2023.10.117.
7. FDA approves osimertinib for locally advanced, unresectable (stage III) non-small cell lung cancer following chemoradiation therapy,” U.S. Food And Drug Administration, Sep. 25, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-osimertinib-locally-advanced-unresectable-stage-iii-non-small-cell-lung-cancer
8. S. Lu et al., “Osimertinib after Chemoradiotherapy in Stage III EGFR -Mutated NSCLC,” New England Journal of Medicine, vol. 391, no. 7, pp. 585–597, Jun. 2024, doi: 10.1056/nejmoa2402614.