The FDA’s recent approval of Rybrevant plus chemo was “groundbreaking” for certain patients with lung cancer, but there is still more work to be done, an expert said.
The recent approval of Rybrevant (amivantamab) plus chemotherapy by the Food and Drug Administration (FDA) is “groundbreaking” for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) who have EGFR exon 20 insertion mutations, an expert told CURE®.
Rybrevant was also FDA-approved for patients with NSCLC who experienced their disease worsening or spreading on or after receiving platinum-based chemotherapy, according to the FDA.
The approval of the regimen is important for patients, “remarkably [because] the combination was superior to chemotherapy alone, and significantly improved progression-free survival,” Dr. Chul Kim, associate professor and thoracic medical oncologist at Georgetown University, said during an interview with CURE®.
Progression-free survival (PFS) is the length of time during and after treatment when patients live without their cancer spreading or worsening, according to the National Cancer Institute.
The improved PFS rates from Rybrevant plus chemotherapy were based on a patient population in the phase 3 PAPILLION trial, presented at the 2023 ESMO Congress.
“This is one of the [most] groundbreaking approvals that we have for patients with EGFR exon 20 insertion mutations, [with] more to come in this field,” Kim said. “The treatment landscape will likely change quite significantly in the next few years for patients, so I remain hopeful.”
Addressing Unmet Needs for EGFR Exon 20 Mutations
Before the approval of Rybrevant with chemotherapy, the standard of care treatment was platinum-doublet chemotherapy, Kim said, which “was not satisfactory in terms of its outcomes and efficacy.”
“Now we have a more effective combination approach that improves treatment outcomes essentially in all domains if that pans out well,” he noted, with the domains referring to PFS, overall survival (time from diagnosis until the end of treatment when patients are still alive) and duration of response (time a tumor responds to treatment without worsening or spreading).
“This is unlikely the only improvement we’re going to see in this space,” said Kim. “However, it’s certainly one of the most important milestones the field has observed in recent years.”
‘More Work Is Still Needed’
Although the approval of Rybrevant plus chemotherapy has led to a “milestone” in the NSCLC space, Kim explained that “there remains a critical need for additional therapies.”
“[Exkivity (mobocertinib)] was approved as second-line treatment and beyond, which is an EGFR exon 20 insertion targeting tyrosine kinase inhibitors, is being withdrawn from the market after a failed phase 3 clinical trial in the frontline setting, unfortunately, so the existence of a [Exkivity] will become limited going forward,” Kim said.
Despite the withdrawal of Exkivity, Kim is “eagerly awaiting” more novel EGFR exon 20 insertion targeting agents that are currently being evaluated in clinical trials.
“I hope to see approvals of some of the promising some of these promising agents. So more work is still needed.”
Side Effects from Rybrevant Plus Chemotherapy
Most side effects that patients may experience with the drug combination could “develop mostly on day one,” Kim stated.
Symptoms and side effects may include chills, shortness of breath, nausea, vomiting and chest discomfort, he explained.
“These are predominantly low-grade toxicities or [side effects] that we see and are limited to first infusion mostly, and rarely happens with subsequent dosing.”
The most common side effect of any severity was rash, Kim noted, which was easily mitigated with a topical steroid cream. Mild side effects that occasionally occurred in patients included lymphedema (swelling in the arms and legs) and diarrhea.
Because the regimen included chemotherapy, some of the side effects were related, such as fatigue, nausea and vomiting, although Kim noted that many of these were effectively mitigated through other medications.
Kim emphasized it’s important for patients to know and understand the side effects they may experience from the treatment combination, specifically with the infusion-related side effects mainly caused by Rybrevant.
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