OncLive’s September Roundup of Key FDA Approvals in Oncology

Below is your guide to the therapeutic options that the FDA has approved in September 2024. The recap comprises topline data that supported the regulatory decisions and features expert insights on what the implications are for clinical practice.

Bortezomib Injectable Scores Approval for Multiple Myeloma and MCL

On September 6, 2024, the FDA gave the green light to a new presentation of bortezomib (Velcade), Boruzu, which is a proteasome inhibitor that reduces the compounding preparation steps usually needed to administer the reference product. The agent will be utilized in patients with multiple myeloma and mantle cell lymphoma. The recommended starting dose for the product is 1.3 mg/m2 and it can be given either intravenously at a concentration of 1 mg/mL or subcutaneously at a concentration of 2.5 mg/mL.

“These ready-to-use injectable presentations are important innovations for oncology providers as they reduce the pharmacy preparation steps for clinicians,” Sean McGowan, vice president of Biosimilars and Branded Oncology, stated in a news release on the announcement.

Subcutaneous Atezolizumab and Hyaluronidase-tqjs Snags Approval for All IV Atezolizumab Indications

The following week, on September 12, 2024, the regulatory agency approved atezolizumab and hyaluronidase-tqjs (Tecentriq Hybreza) for subcutaneous injection for all adult indications as the intravenous formulation of atezolizumab (Tecentriq), which includes non–small cell lung cancer (NSCLC), small cell lung cancer, hepatocellular carcinoma, melanoma, and alveolar soft part sarcoma.

Data from the phase 3 IMscin001 trial (NCT03735121) indicated that the geometric mean ratio of subcutaneous and intravenous atezolizumab for cycle 1 observed trough serum concentration was 1.05 (90% CI, 0.88-1.24) in patients with locally advanced or metastatic NSCLC. Moreover, the area under the curve from day 0 to 21 was 0.87 (90% CI, 0.83-0.92). Overall response rates (ORRs) and progression-free survival (PFS) and overall survival (OS) benefits were similar for both formulations.

“By enabling subcutaneous administration for a cancer immunotherapy, [atezolizumab and hyaluronidase] now offers patients with multiple cancer types and their physicians greater flexibility and choice of treatment administration,” Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development at Genentech, stated in a news release.

Adjuvant Ribociclib Wins Approval in HR+/HER2– Breast Cancer

On September 17, 2024, ribociclib (Kisqali) plus an aromatase inhibitor (AI) was approved for the adjuvant treatment of patients with hormone receptor–positive, HER2-negative stage II and III early breast cancer at high risk of recurrence, including those with node-negative disease.

The decision was supported by data from the phase 3 NATALEE trial (NCT03701334) in which the combination of ribociclib and a nonsteroidal AI (NSAI) in the form of letrozole (Femara) or anastrozole (Arimidex) with or without goserelin (Zoladex; n = 2549) resulted in a significant improvement in invasive disease-free survival (iDFS) vs an NSAI alone with or without goserelin (n = 2552; HR, 0.749; 95% CI, 0.749; 95% CI, 0.628-0.892). The 36-month iDFS rates in the respective arms were 90.7% (95% CI, 89.3%-91.8%) and 87.6% (95% CI, 86.1%-88.9%).

“Although there are some new learning points that we’re going to have to discuss, this [approval] is exciting because there are now more opportunities for patients [in the curative setting] to get [therapy] from this new indication,” Bora Lim, MD, told OncLive® in an exclusive interview. “There will have to be a lot of heart-to-heart discussions between physicians and their patients [now that we have this approval].” Lim, who is an associate professor in the Department of Breast Medical Oncology, chief of the Translational Research section, and director of Translational Research at The University of MD Anderson Cancer Center in Houston, Texas, further discussed the significance of the approval:

In another interview, Virginia G. Kaklamani, MD, DSc, a professor of medicine in the Division of Hematology-Medical Oncology at The University of Texas Health Science Center San Antonio and leader of the Breast Cancer Program at the Mays Cancer Center of UT Health San Antonio MD Anderson Cancer Center, discussed the optimal role of adjuvant ribociclib plus endocrine therapy in this patient population.

Pembrolizumab Plus Chemo Gains Approval for Malignant Pleural Mesothelioma

On the same day, pembrolizumab (Keytruda) plus pemetrexed and platinum chemotherapy was approved by the FDA for the first-line treatment of patients with unresectable advanced or metastatic malignant pleural mesothelioma based on findings from the phase 2/3 KEYNOTE-483 trial (NCT02784171).

The addition of pembrolizumab to chemotherapy (n = 222) provided a significant OS benefit over chemotherapy alone (n = 218), at a median of 17.3 months (95% CI, 14.4-21.3) and 16.1 months (95% CI, 13.1-18.2), respectively (HR, 0.79; 95% CI, 0.64-0.98; P = .0162). The addition of pembrolizumab to chemotherapy also resulted in a PFS improvement (HR, 0.80; 95% CI, 0.65-0.99; P = .0194).

“We’re pleased to offer a new first-line treatment option for adult patients with unresectable advanced or metastatic malignant pleural mesothelioma, a disease where prognoses are generally poor,” Gregory Lubiniecki, MD, vice president of oncology clinical research at Merck Research Laboratories, stated in a news release. “This milestone underscores our commitment to advancing research for patients with difficult-to-treat tumors.”

Amivantamab Plus Chemo Gets Green Light for EGFR+ Advanced NSCLC Post EGFR Inhibition

A couple of days later, on September 19, 2024, the regulatory agency approved amivantamab-vmjw (Rybrevant) plus carboplatin/pemetrexed for adult patients with locally advanced or metastatic NSCLC and EGFR exon 19 deletions or exon 21 L858R substitution mutations whose disease has progressed on or following EGFR inhibition.

The decision was based on findings from the phase 3 MARIPOSA-2 study (NCT04988295) in which the amivantamab combination (n = 131) significantly improved PFS vs chemotherapy alone (n = 263), at a median PFS of 6.3 months (95% CI, 5.6-8.4) by blinded independent central review and 4.2 months (95% CI, 4.0-4.4), respectively (HR, 0.48; 95% CI, 0.36-0.64; P < .0001). The ORRs in the respective arms were 53% (95% CI, 44%-62%) and 29% (95% CI, 23%-35%; P < .0001).

“Rybrevant plus chemotherapy may address the most common mechanisms of treatment resistance to third-generation EGFR TKIs, such as osimertinib [Tagrisso], in the first line,” Martin Dietrich, MD, PhD, oncologist at Cancer Care Centers of Brevard, stated in a news release. “This multitargeted combination extended PFS and improved overall response compared to chemotherapy alone, offering an important and effective new second-line option for patients.”

Isatuximab Plus VRd Gets Approval for Newly Diagnosed, Transplant-Ineligible Multiple Myeloma

The next day, on September 20, 2024, the combination of isatuximab-irfc (Sarclisa), bortezomib, lenalidomide (Revlimid), and dexamethasone (VRd; Isa-VRd) was approved by the FDA for use in adult patients with newly diagnosed multiple myeloma who were not candidates for autologous stem cell transplant. Data from the phase 3 IMROZ trial (NCT03319667), which were presented during the 2024 ASCO Annual Meeting, showed that Isa-VRd (n = 265) improved PFS vs VRD alone (n = 181). The median PFS with isatuximab was not yet reached (NR; 95% CI, NR-NR) vs 54.34 months (95% CI, 45.207-NR) without (HR, 0.596; 98.5% CI, 0.406-0.876; P < .001).

“The IMROZ study may potentially change the way we treat transplant-ineligible patients in the newly diagnosed setting,” Noa Biran, MD, associate professor of medicine at Hackensack Meridian School of Medicine and physician in the Division of Multiple Myeloma at John Theurer Cancer Center, Hackensack Meridian Health, said in an interview with OncLive. “The standard of care, up until now, was the combination of daratumumab [Darzalex], lenalidomide, and dexamethasone for patients who are transplant ineligible. The IMROZ study compared VRd with or without isatuximab. This is the first time that a proteasome inhibitor [PI] was incorporated into the treatment regimen for patients with transplant-ineligible myeloma. [The trial] proved both the efficacy and feasibility of the delivery of a quadruplet regimen. I think a PI is important, especially in high-risk patients who are transplant ineligible.”

Thierry Facon, MD, professor of hematology in the Department of Hematology at Lille University Hospital, also shed some light on the clinical implications of the study in the following interview:

Moreover, in an episode of OncLive On Air®, Robert Z. Orlowski, MD, PhD, sat down with us to discuss the key efficacy data from the trial, the quality-of-life impact of Isa-VRd, and how data from the trial could pave the way for additional research with quadruplet regimens in the transplant-ineligible setting. Orlowski holds the Florence Maude Thomas Cancer Research Professorship in the Department of Lymphoma/Myeloma, is the director of the Section of Myeloma, and is a professor in the Department of Experimental Therapeutics in the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center in Houston.

Osimertinib Wins Approval for Locally Advanced, Unresectable EGFR+ NSCLC After Chemoradiation

On September 25, 2024, the regulatory agency awarded osimertinib (Tagrisso) approval for use in adult patients with locally advanced, unresectable, stage III NSCLC whose disease has not progressed during or after concurrent or sequential platinum-based chemoradiation therapy and whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations. Findings from the phase 3 LAURA trial (NCT03521154) supported the decision. Osimertinib (n = 143) significantly improved PFS vs placebo (n = 73) in this population, at a median of 39.1 months (95% CI, 31.5-not estimable) and 5.6 months (95% CI, 3.7-7.4), respectively (HR, 0.16; 95% CI, 0.10-0.24; P < .001).

In a special episode of OncLive On Air conducted in partnership with Two Onc Docs, Samantha A. Armstrong, MD, and Karine Tawagi, MD, delved into LAURA and discussed questions raised by the trial’s design and its findings. Dr Armstrong is a hematologist/oncologist and assistant professor of clinical medicine at Indiana University Health in Indianapolis. Dr Tawagi is a hematologist/oncologist and assistant professor of clinical medicine at the University of Illinois in Chicago.

Additionally, in an episode of Oncology Unplugged, Chandler Park, MD, a genitourinary medical oncologist at the Norton Cancer Institute in Louisville, Kentucky, sat down with Tejas Patil, MD, an assistant professor of medicine/medical oncology at the University of Colorado School of Medicine – Anschutz Medical Campus in Aurora, to discuss pivotal updates from the 2024 ASCO Annual Meeting, which included the LAURA trial.

Selpercatinib Snags Full Approval for RET Fusion+ Medullary Thyroid Cancer

On September 27, 2024, the FDA granted traditional approval to selpercatinib (Retevmo) for adult and pediatric patients aged 2 years and older with advanced or metastatic medullary thyroid cancer harboring a RET mutation who require systemic treatment.

The decision was supported by findings from the phase 3 LIBRETTO-531 study (NCT04211337) in which selpercatinib (n = 193) resulted in improved PFS vs physician’s choice of cabozantinib (Cabometyx) or vandetanib (Caprelsa; n = 98). The median PFS was NR (95% CI, NE-NE) in the investigative arm vs 16.8 months (95% CI, 12.2-25.1) in the control arm (HR, 0.280; 95% CI, 0.165-0.475; P < .0001). The 12-month PFS rates in the respective arms were 86.8% (95% CI, 79.8%-91.6%) and 65.7% (95% CI, 51.9%-76.4%). Selpercatinib previously received accelerated approval from the regulatory agency in May 2020 for several indications.

In a past interview, Julien Hadoux, MD, PhD, a medical oncologist and attending physician at Gustave Roussy, in Villejuif, France, discussed the efficacy of selpercatinib in advanced, kinase inhibitor–naive, RET-mutant medullary thyroid cancer, as reported in the preplanned interim analysis of LIBRETTO-531: