A schedule of once-daily radiation therapy (66 Gy) was no better than a twice-daily schedule (45 Gy) for optimization of chemoradiotherapy in patients with limited-stage small cell lung cancer (SCLC), according to the eagerly anticipated results of the phase III ­CONVERT trial, presented at the 2016 ASCO Annual Meeting.¹

This is the largest study ever completed in limited-stage SCLC. The results support the use of either regimen for SCLC patients with a good performance status.

— Corinne Faivre-Finn, MD, PhD

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CONVERT is reportedly the largest multicenter, international, randomized, phase III trial ever conducted in this disease group, recruiting patients in Europe and Canada. It evaluated the optimization of chemoradiotherapy in limited-stage SCLC. Investigators had high hopes that this trial would define a new standard chemoradiotherapy regimen for patients with limited-stage SCLC and a good performance status, explained lead author Corinne Faivre-Finn, MD, PhD, of the University of Manchester, Institute of Cancer Sciences, Manchester, United Kingdom.

At a median follow-up of 45 months, 2-year survival was 56% for the twice-daily radiation therapy vs 51% for the once-daily radiation therapy. Median overall survival was 30 months vs 25 months, a difference that is not statistically significant.

“This is the largest study ever completed in limited-stage SCLC. It was challenging to accrue patients with this disease. In this trial, survival was higher than previously reported in other trials of this patient population, and radiation toxicities were lower than expected. The results support the use of either regimen for SCLC patients with a good performance status,” Prof. Faivre-Finn stated.

Study Details and Findings

The study enrolled 547 patients with histologically or cytologically proven SCLC recruited from 73 centers in 7 European countries and Canada between 2008 and 2013. Patients were randomized to receive either concurrent twice-daily radiation therapy (45 Gy in 30 twice-daily fractions over 3 weeks) or concurrent once-daily radiation therapy (66 Gy in 33 once-daily fractions over 6.5 weeks), both starting on day 22 of cycle 1. Chemotherapy was given with either four or six cycles of cisplatin/etoposide according to investigator’s prespecified choice; the majority opted for four cycles. Patients with any response were offered prophylactic cranial radiation therapy.

About 30% of people with SCLC present with limited-stage or stages I to III cancer; the standard of care is concurrent chemoradiotherapy, but there is a lack of consensus on standard radiation therapy, explained Prof. Faivre-Finn.

All analyses were done on an intention-to-treat basis. A total of 25 patients in the twice-daily radiation therapy group and 32 in the once-daily radiation therapy group did not get concurrent chemoradiation therapy.

Patient characteristics were well balanced in both arms of the study, Median age was about 63 years; 15% were older than age 70; almost 50% were female; the majority had a performance status of 0 or 1 and were ex-smokers or current smokers. Eighty percent of patients had stage III disease.

There was no statistically significant overall survival difference between the groups. One–year survival was 83% for the twice-daily radiation therapy arm and 76% for the once-daily radiation therapy arm.

No statistically significant differences between the two groups were reported for the rates of progression-free survival or local or metastatic disease progression.

Toxicity

Adverse events were not significantly different between the two groups as well, with the exception of more neutropenia in patients treated with twice-daily radiation therapy. High-dose radiation therapy to the lungs and esophagus in the once-daily arm did not seem to translate to a significant difference between the arms in terms of esophagitis or pneumonitis. There was one death in the twice-daily group and two in the once-daily group due to radiation pneumonitis.

Few patients developed severe late toxicity, concluded Prof. Faivre-Finn. ■

Disclosure: Prof. Faivre-Finn received institutional research funding from AstraZeneca and Merck Sharp & Dohme and received travel expenses from Merck Sharp & Dohme.

Reference

1. Faivre-Finn C, Snee M, Ashcroft L, et al: CONVERT: An international randomised trial of concurrent chemo-radiotherapy comparing twice-daily and once-daily radiotherapy schedules in patients with limited stage small cell lung cancer and good performance status. 2016 ASCO Annual Meeting. Abstract 8504.