Küçük hücreli dışı (exon 20 insertion mutasyonu) Akciğer kanserinde yeni tedavi seçeneği olarak Amivantamab ve Kemoterapi kombinasyonu

Küçük hücreli dışı (exon 20 insertion mutasyonu) Akciğer kanserinde yeni tedavi seçeneği olarak Amivantamab ve Kemoterapi kombinasyonu

Evre IV akciğer kanserinde bireye özgü tedavide yüz güldüren sonuçlar mevcut.

Akciğer kanseri tedavisine başlamadan önce artık standart istenmesi gereken mutasyonlar mevcut. Akciğer kanseri tedavisine başlamadan önce bakılması gereken mutasyonlar EGFR, ALK, KRAS, ROS1, BRAF, NTRK1/2/3, METex14skipping, RET, ERBB2 (HER2) ve ayrıca PD-L1 düzeyi tedaviye karar vermede önemli bir belirteç.

EGFR exon 20 insertion mutasyonu evre IV küçük hücreli dışı akciğer kanserinde yaklaşık %4 oranında görülür. Bu mutasyona sahip hastalar genel olarak kötü seyre sahiptir.

Yeni bir tedavi kombinasyonu bu hasta grubunda daha iyi sonuç almamızın mümkün olduğunu gösterdi.

Bu kombinasyonun etkili olduğu diğer bir grup hasta, yaklaşık %4 oranında görülen ve kötü seyreden exon 20 insertion mutasyonu olan hastalar.

Amivantamab ile Karboplatin+ pemetrexet kombinasyonu ile bu grup hastaların %73 oranında yanıt alındı görüldü ve aynı zamanda hastalıksız süreyi %60 azalttığı saptandı.

İlaç ilişkili cilt toksisitesi, tırnak değişiklikleri, mukozit, iştah azalması yan etkilerin artığı ve bunların yöneltilebilir olduğu saptandı.

Bu çalışma sonrası, Amerika Birleşik Devletleri Gıda ve İlaç Dairesi (FDA) tarafından, EGFR exon 20 insertion mutasyonu evre IV küçük hücreli dışı akciğer kanserinde, Amivantamab ile Karboplatin+ pemetrexet kombinasyonu yeni tedavi seçeneği olarak kullanılması onaylandı.

Kaynak

The FDA has approved amivantamab-vmjw (Rybrevant) plus carboplatin and pemetrexed for the frontline treatment of patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) harboring EGFR exon 20 insertion mutations, as detected by an FDA-approved test.1,2

The regulatory agency also granted full approval to amivantamab in adult patients with locally advanced or metastatic NSCLC harboring EGFR exon 20 insertion mutations who experienced progression on or following platinum-based chemotherapy.

Data from the phase 3 PAPILLON study (NCT04538664) showed that amivantamab plus chemotherapy (n = 153) significantly improved progression-free survival (PFS) vs chemotherapy alone (n = 155), at a median of 11.4 months (95% CI, 9.8-13.7) vs 6.7 months (95% CI, 5.6-7.3), respectively (HR, 0.40; 95% CI, 0.30-0.53; P < .0001).

The overall survival (OS) data were immature at the current analysis, with only 44% of prespecified deaths for the final analysis reported; however, no trend toward a detriment with amivantamab/chemotherapy has been observed.

Understanding PAPILLON: Eligibility, Treatment, Objectives

The randomized, open-label, multicenter study included patients with treatment-naive, locally advanced or metastatic NSCLC harboring EGFR exon 20 insertion mutations who had measurable disease by RECIST v1.1 criteria. Patients were required to have an ECOG performance status of 0 or 1 and acceptable organ and bone marrow function.

Notably, those with brain metastases at the time of screening were allowed to enroll if they were definitively treated, clinically stable, asymptomatic, and had not been receiving corticosteroids for at least 2 weeks before undergoing randomization.

Those with a history of, or active, interstitial lung disease were excluded.

Study participants (n = 308) were randomly assigned 1:1 to receive amivantamab plus chemotherapy or chemotherapy alone.

Amivantamab was given intravenously (IV) at a dose of 1400 mg for those who weighed under 80 kg or 1750 mg in those who weighed 80 kg or more once weekly for 4 weeks and then every 3 weeks at 1750 mg or 2100 mg, respectively, starting at week 7. The agent was continued until disease progression or intolerable toxicity. Moreover, IV carboplatin was given at area under the concentration-time curve 5 mg/mL/min once every 3 weeks for up to 12 weeks, and IV pemetrexed was given at 500 mg/m2 once every 3 weeks until progressive disease or intolerable toxicity.

Key stratification factors were performance status (0 vs 1) and the presence of prior brain metastases (yes vs no).

Those in the chemotherapy-alone arm who experienced disease progression were able to crossover to received amivantamab monotherapy.

PFS served as the trial’s primary efficacy outcome measure, and was evaluated by blinded independent central review. Other efficacy outcome measures included overall response rate, duration of response, and OS.

The median patient age was 62 years (range, 27-92), and 40% of patients were aged 65 years or older. Fifty-eight percent of patients were female and most patients were Asian (61%) and not Hispanic or Latino (93%). In terms of ECOG performance status at baseline, 35% had a status of 0, and 65% had a status of 1. The majority (84%) of patients had stage IV disease at the time of their initial diagnosis. Additionally, 58% of patients were never smokers and 23% had a history of brain metastases.

Additional Efficacy Data

The addition of amivantamab to chemotherapy resulted in an ORR of 67% (95% CI, 59%-75%) vs 36% (95% CI, 29%-44%) with chemotherapy alone. Of those who responded in the amivantamab arm, 4% had a complete response (CR) and 63% had a partial response (PR); these respective rates in the chemotherapy-alone arm were 1% and 36%. The median duration of response with amivantamab plus chemotherapy was 10.1 months (95% CI, 8.5-13.9) vs 5.6 months (95% CI, 4.4-6.9) with chemotherapy alone.

Safety Findings

The median exposure to amivantamab plus chemotherapy was 9.7 months (range, 0-26.9) and the median exposure to chemotherapy alone was 6.7 months (range, 0-25.3).

Thirty-seven percent of patients who received the amivantamab combination experienced serious adverse reactions. Moreover, 4.6% of patients experienced fatal adverse reactions in the form of pneumonia, cerebrovascular accident, cardiorespiratory arrest, COVID-19, sepsis, and death not otherwise specified.

Dose reductions or interruptions of amivantamab due to an adverse effect (AE) were required for 36% and 64% of patients, respectively. Eleven percent of patients permanently discontinued amivantamab because of an AE.

In the amivantamab/chemotherapy arm, the most common AEs experiened by at least 10% of patients included rash (all grade, 90%; grade 3/4, 19%), nail toxicity (62%; 7%), dry skin (17%; 0%), stomatitis (43%; 4%), constipation (40%; 0%), nausea (36%; 0.7%), vomiting (21%; 3.3%), diarrhea (21%; 3%), hemorrhoids (12%; 1%), abdominal pain (11%; 0.7%), infusion-related reaction (42%; 1.3%), fatigue (42%; 6%), edema (40%; 1.3%), pyrexia (17%; 0%), reduced appetite (36%; 2.6%), COVID-19 (24%; 2%), pneumonia (13%; 5%), hemorrhage (18%; 0.7%), cough (17%; 0%), dyspnea (11%; 1.3%), weight decreased (14%; 0.7%), dizziness (11%; 0%), and insomnia (11%; 0%).

References

FDA approves amivantamab-vmjw for EGFR exon 20 insertion-mutation non-small cell lung cancer indications. FDA. March 1, 2024. Accessed March 1, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-amivantamab-vmjw-egfr-exon-20-insertion-mutated-non-small-cell-lung-cancer-indications

Rybrevant. Prescribing information. Janssen Biotech, Inc.; 2024. Accessed March 1, 2024. https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/761210s003lbl.pdf