CHICAGO – Maintenance erlotinib was no more efficacious than observation when given to women with ovarian or related cancers who had no evidence of progression after receiving first-line platinum-based chemotherapy.

The 835 women studied in a randomized, phase III trial had a median progression-free survival of about 1 year and an overall survival median of about 4.5 years regardless of whether they were assigned to erlotinib – an oral inhibitor of the EGFR (epidermal growth factor receptor) tyrosine kinase – or simple observation.

The findings were similar in patient subgroups who were stratified according to a wide range of factors, such as stage and (in preliminary analyses) tumor EGFR positivity, investigators reported at the annual meeting of the American Society of Clinical Oncology.

"Maintenance erlotinib after first-line chemotherapy in patients with ovarian, peritoneal, or fallopian tube cancer did not increase progression-free survival nor overall survival," said lead investigator Dr. Ignace B. Vergote. Moreover, a quarter of patients stopped the drug early because of adverse effects.

"At this moment, we cannot identify a subgroup that might benefit from erlotinib maintenance therapy after first-line chemotherapy for ovarian cancer, but we are continuing to look at immunohistochemistry and FISH [fluorescence in situ hybridization] analysis," added Dr. Vergote, chairman of the Leuven (Belgium) Cancer Institute and head of the department of obstetrics and gynecology and gynecologic oncology at the Catholic University of Leuven.

Discussant Dr. Michael V. Seiden of the Fox Chase Cancer Center in Philadelphia noted that there was "a compelling body of basic and preclinical evidence that made the advent or launch of this study very logical." For example, research had shown a correlation between high tumor EGFR levels and poor prognosis in ovarian cancer, as well as an association– in various cancers – of EGFR mutations or expression with response to therapies targeting this receptor.

"Unfortunately, the addition of erlotinib as part of a maintenance schedule did not budge progression-free survival or overall survival," he said. "Perhaps now, in 2012, with the value of ... hindsight, one might have made this prediction, in that there have been now numerous negative single-arm studies or nearly negative single-arm studies with both small-molecule inhibitors and monoclonal antibodies" against EGFR.

Women enrolled in the EORTC (European Organisation for Research and Treatment of Cancer) 55041 trial – a joint effort of six cooperative groups – had high-risk stage I, or stages II to IV epithelial ovarian, primary peritoneal, or fallopian tube cancer and at least stable disease as of the end of first-line platinum-based chemotherapy.

They were assigned to either erlotinib (Tarceva) 150 mg daily for 2 years or observation. Erlotinib is currently approved by the Food and Drug Administration for the treatment of non–small cell lung cancer and pancreatic cancer.

Demographic and clinical data showed that about 62% of patients had serous tumor histology. Nearly all (96%) had received carboplatin and paclitaxel as their first-line therapy. Roughly 70% had had primary debulking surgery, whereas 30% had received neoadjuvant therapy and interval debulking surgery; there was no evidence of disease at surgery in 48% of the former and 62% of the latter.

Overall, 25% of patients in the erlotinib group stopped therapy early because of unacceptable adverse events (mainly rash), Dr. Vergote reported.

Main results showed that with a median follow-up of 4.3 years, erlotinib and observation were statistically indistinguishable in terms of median progression-free survival (12.7 vs. 12.4 months), with progression defined according to RECIST criteria or CA (cancer antigen) 125 levels, and overall survival (51 vs. 59 months). The findings were similar in subgroups stratified by stage, age, performance status, and response at the end of first-line chemotherapy.

Patients in the erlotinib group were more likely to experience grade 3/4 diarrhea (5% vs. 1%) and rash (13% vs. 0%).

Preliminary tumor mutational analysis in 318 patients showed that the most common was PI3KCA mutation (present in about 4% of cases), followed by KRAS mutation (present in about 3%). Only about 1% had an EGFR mutation, and mutations of NRAS and BRAF were similarly uncommon.

Progression-free survival was better for patients having any of these mutations than for those having none (P = .04). But among the former, there was no significant benefit of erlotinib over observation.

Progression-free survival was also similar across subgroups of patients whose tumors were EGFR positive and negative according to either immunohistochemistry or FISH.

Analyses failed to identify any significant relationship between the development of rash during erlotinib therapy and progression-free survival. The investigators plan to analyze quality of life data.

Dr. Vergote disclosed no relevant conflicts of interest. Dr. Seiden disclosed no relevant conflicts of interest.

Erlotinib Fails as Maintenance Therapy for Ovarian Cancer