Promising Findings Seen With Neratinib in HER2-Mutant Cervical Cancer


Neratinib demonstrated durable responses and disease control and a manageable safety profile in patients with metastatic&nbsp;<em>HER2</em>-mutant cervical cancer, according to results from the ongoing phase II SUMMIT basket trial.

Anishka D'Souza, MD

Neratinib (Nerlynx) demonstrated durable responses and disease control and a manageable safety profile in patients with metastaticHER2-mutant cervical cancer, according to results from the ongoing phase II SUMMIT basket trial.

Treatment with the agent led to a clinical benefit rate (CBR) of 54.5% in patients withHER2-mutant cervical cancer, said Anishka D'Souza, MD, assistant professor of clinical medicine, Keck School of Medicine, USC.

Among the 11 patients treated in the updated interim efficacy results, 3 experienced a partial response (PR) to treatment, for an objective response rate (ORR) of 27.3% (95% CI, 6.0-61.0). Duration of response for each patient was 5.6 months, 5.9 months, and 7.4 months, with the longest responder still on treatment at this time.

SomaticHER2mutations are observed in approximately 5% of metastatic cervical cancers, are oncogenic, and are associated with poor prognoses, D'Souza said. &ldquo;Recurrent cervical cancer is a relatively treatment-resistant disease if not resectable, with limited treatment options and few long-term, durable responses,&rdquo; she added. &ldquo;Most of these women will die of their disease in a few years, so there is a need for additional treatment options.&rdquo;

However, neratinib—an oral, irreversible tyrosine kinase inhibitor ofEGFR(ERBB1),HER2(ER882), andHER4(ER884)—has demonstrated single-agent clinical activity in multipleHER2-mutant cancers.

In the trial—which is evaluating the agent as either a monotherapy or in combination with paclitaxel or trastuzumab (Herceptin) for the treatment of biliary tract, cervical, ovarian, salivary gland, bladder, HR-positive and -negative breast, lung,KRAS/NRAS/BRAFwild-type colorectal cancers, and solid tumors—patients withHER2-mutant cervical cancer received 240 mg of oral neratinib once daily.

Key inclusion criteria were the presence of a documented HER2 mutation and ECOG status of 0 to 2. Patients were ineligible if they had prior treatment with any pan-HER TKI or had symptomatic or unstable brain metastases.

ORR at first post-baseline tumor assessment served as the primary endpoint. Secondary endpoints included confirmed ORR, CBR, progression-free survival (PFS), safety, and biomarkers.

Eleven patients withHER2-mutant cervical cancer were evaluable for efficacy. Median age was 50 years (range, 29-64), and the majority were white (54.5%), and had an ECOG score of 1 (72.7%) and M0 disease (63.6%). Overall, 72.7% of patients had adenocarcinoma, 18.2% had squamous cell carcinoma, and 9.1% had adenosquamous carcinoma.

The median number of total prior regimens was 2 (range, 1-4), including 9 patients (81.8%) with radiation, 7 (63.6%) with surgery, and 6 (54.5%) with bevacizumab.

Six patients derived clinical benefit from the agent, including the 3 PRs as well as 3 patients who experienced stable disease for 16 weeks or more, for a CBR of 54.5% (95% CI, 23.4-83.3). Median PFS was 7 months (95% CI, 0.7-20.1).

Common AEs of any grade included diarrhea (81.8%), nausea (54.5%), decreased appetite (45.5%), abdominal pain (36.4%), dyspnea (36.4%), epistaxis (27.3%), headache (27.3%), malaise (27.3%), peripheral edema (27.3%), pain (27.3%) and vomiting (27.3%). Because diarrhea was the most common AE, high-dose loperamide prophylaxis was mandatory during cycle 1.

No treatment discontinuations or reductions occurred within the cervical cancer cohort. One grade 3 diarrhea occurred in the group, but the duration of the AE was only 1 day.

D'Souza also noted thatHER2mutations can be detected by readily available next-generation assays. Therefore, future directions include the initiation of a liquid biopsy pilot screening program (HER-Seq) to identify patients withHER2mutations. &ldquo;This is an ongoing study and we are continuing to enroll patients to expand our data set,&rdquo; she added.


D&rsquo;Souza A, Roman LD, Saura C, et al. Neratinib in patients with HER2-mutant, metastatic cervical cancer: findings from the phase 2 SUMMIT &lsquo;basket&rsquo; trial. Presented at: 2019 SGO Annual Meeting. March 16-19, 2019; Honolulu, HI. Abstract 18.

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