Early trial results in lung cancer

By Shreeya Nanda, Senior medwireNews Reporter

Results from early phase trials investigating different therapeutic agents in lung cancer patients were presented during the third Presidential Session at the European Cancer Congress in Vienna, Austria. Here we summarise two studies reported at the session.

Erlotinib plus bevacizumab promising in EGFR T790M-positive advanced NSCLC patients

Rolf Stahel, from University Hospital Zurich in Switzerland, presented the findings of the BELIEF trial [1] on behalf of his fellow investigators from the Spanish Lung Cancer Group and the European Thoracic Oncology Platform. The phase II trial enrolled 109 patients with metastatic or locally advanced non-squamous non-small-cell lung cancer (NSCLC) harbouring activating epidermal growth factor receptor (EGFR) mutations (either the exon 19 deletion or the exon 21 L858R point mutation).

Of these, 37 (33.9%) patients also carried the EGFR T790M mutation at baseline, while the remaining 72 participants were negative for T790M.

Patients were treated with a combination of everolimus and bevacizumab on the basis of previous preclinical results suggesting that inhibiting both the EGFR and vascular EGFR pathways could be beneficial in the presence of the T790M mutation, explained Stahel.

After a median follow-up of 17.5 months, progression-free survival (PFS) was a median of 13.8 months in the overall cohort, with times of 16.0 and 10.5 months for the T790M-positive and -negative groups, respectively. The corresponding 1-year PFS rates were 56.7%, 72.4% and 49.4%.

Complete responses were achieved by 6.4% of all study participants, 8.1% of those positive for T790M and 5.6% of T790M-negative patients, while partial responses were achieved by 69.7%, 62.2% and 73.6% of patients, respectively.

Stahel reported that there were “no unexpected toxicities” with this combination. The most frequent high-grade adverse events were grade 3 hypertension in 34.9% of patients and grade 3 maculopapular rash in 18.9%.

The study reached their predefined endpoint for success, a 1-year PFS rate of 63% in the T790M-positive group, he said, adding that updated efficacy and overall survival results will be presented at a later date.

Targeting DLL3 shows promise in SCLC setting

Maria Pietanza, from the Memorial Sloan Kettering Cancer Center in New York, USA, shared the safety and activity data from the phase I trial of single-agent rovalpituzumab tesirine in patients with small-cell lung cancer (SCLC) who had progressed after using up to two previous therapies [2].

Rovalpituzumab tesirine is an antibody–drug conjugate that targets the Notch ligand delta-like protein 3 (DLL3) found in SCLC cells but not healthy tissue, she explained.

The trial accrued 73 participants, among whom those treated at doses of 0.8 mg/kg and 0.4 mg/kg experienced respectively acute and chronic dose-limiting toxicities (specifically thrombocytopenia and serosal effusion). And therefore the phase Ib expansion cohorts assessed the maximum tolerated doses of 0.2 mg/kg once every 3 weeks and 0.3 mg/kg once in 6 weeks.

Pietanza said in the press briefing that the adverse-effect profile of the study drug was similar to other chemotherapeutic agents, with fatigue the most common toxicity of any grade, observed in 28% of the 69 evaluable patients. She highlighted, however, that pleural effusion (13%) and photosensitivity (12%) were toxicities unique to rovalpituzumab tesirine.

Among the 53 participants evaluable for response, 23% achieved an overall response.

When study participants were stratified by DLL3 expression, 27of 49 patients with available tumour samples had high levels of DLL3, and 44% of these patients attained either a complete or partial response to the treatment.

And the overall response rate (ORR) was similar whether the participants with high levels of DLL3 received rovalpituzumab tesirine as second- or third-line treatment, at 44% and 45%, respectively. By contrast, the corresponding ORRs in the overall cohort were 24% and 20%.

Moreover, the responses were durable for those who achieved them – in the 0.3 mg/kg cohort, ongoing responses were observed at 189 days from the initial computed tomography scan, and overall survival “remains prolonged”, at an average of 236 days, she reported.

Pietanza presented a case study of a patient who had a confirmed response after receiving two doses of rovalpituzumab tesirine. In light of the ongoing response and as the tumour was restricted to the adrenal gland, the patient underwent an adrenalectomy.

Pathological review showed a 95% treatment response on the tumour, and the adrenal gland was negative for the proliferative index marker Ki67, which suggests that the study drug affects tumour-initiating cells, she said. The patient remains alive and disease free at over a year since treatment initiation.

A second patient also achieved a confirmed response after two doses and remains alive over 300 days after the first administration of rovalpituzumab tesirine.

Pietanza therefore concluded that “rovalpituzumab tesirine has single-agent activity in SCLC” and that response rates are greater and more durable in patients with high DLL3 levels, suggesting that “DLL3 may be the first predictive biomarker associated with drug efficacy in SCLC”.

The results “support biomarker-guided phase II studies”, she added.

medwireNews is an independent medical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2015


1. Stahel RA, Dafni U, Gautschi O, et al. A phase II trial of erlotinib (E) and bevacizumab (B) in patients with advanced non-small-cell lung cancer (NSCLC) with activating epidermal growth factor receptor (EGFR) mutations with and without T790M mutation. The Spanish Lung Cancer Group (SLCG) and the European Thoracic Oncology Platform (ETOP) BELIEF trial. Presented at: European Cancer Congress; Vienna, Austria: 25–29 September 2015; 3BA

2. Pietanza MC, Spigel D, Bauer TM, et al. Safety, activity, and response durability assessment of single agent rovalpituzumab tesirine, a delta-like protein 3 (DLL3)-targeted antibody drug conjugate (ADC), in small cell lung cancer (SCLC). Presented at: European Cancer Congress; Vienna, Austria: 25–29 September 2015; 7LBA

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