ITACA Trial: No Survival Benefit for Tailoring Adjuvant Chemotherapy in NSCLC

Get Permission

Tailoring adjuvant chemotherapy based on the expression of two molecular markers did not lead to a survival advantage in patients with completely resected stage II to III non–small cell lung cancer (NSCLC) in the phase III ITACA trial. This result was presented during the virtual edition of the International Association for the Study of Lung Cancer 2020 World Conference on Lung Cancer Singapore.1

Silvia Novello, MD, PhD

Silvia Novello, MD, PhD

“Adjuvant chemotherapy customization based on the primary tumor tissue mRNA expression of ERCC1 and thymidylate synthase did not significantly improve overall survival or recurrence-free survival. There was a non–statistically significant trend for overall survival favoring the customized arm,” said Silvia Novello, MD, PhD, Professor of Medical Oncology at the University of Torino at San Luigi Gonzaga Hospital, Orbassano, Italy.

Toxicity was, however, more manageable with customization of treatment. Grade 3 or 4 adverse events occurred in 32.6% of patients in the tailored-therapy arm and 45.9% of those in the control arm (hazard ratio [HR] = 0.57; P < .001). “It is important to underline that treatment customization significantly improved the toxicity profile without compromising efficacy,” Dr. Novello said.

In the ITACA trial, Dr. Novello and other European researchers investigated whether an adjuvant pharmacogenomics-driven approach could improve overall survival in patients with resected NSCLC. They specifically evaluated mRNA expression levels and the predictive utility of excision repair cross-complementing group 1 (ERCC1) and thymidylate synthase.

“Several reports have linked cisplatin, carboplatin, and oxaliplatin resistance to high ERCC1 mRNA levels in tumors. Although the drug-target relationship between thymidylate synthase and tumor response to fluorouracil has been challenged, lower thymidylate synthase expression in lung adenocarcinoma was associated with higher efficacy of cisplatin plus pemetrexed and inferior efficacy in small cell lung cancer,” she explained.

ITACA Design

The study enrolled 773 patients from 31 European centers who had undergone surgical resection for stage II to III NSCLC between 2008 and 2014. Genomic analyses were performed soon after surgery, and patients were assigned to one of four genomic subgroups. In each subgroup, patients were randomly assigned to receive investigator’s choice of platinum-based chemotherapy or tailored treatment defined by biomarkers, as follows:

  • High thymidylate synthase (n = 148): single-agent docetaxel
  • Low thymidylate synthase (n = 43): pemetrexed
  • Low ERCC1 expression: cisplatin/gemcitabine if thymidylate synthase was high (n = 101) and cisplatin/pemetrexed if thymidylate synthase was low (n = 92)
  • Control arm: cisplatin/gemcitabine (n = 159), cisplatin/vinorelbine (n = 123), or other (n = 28).

After a median follow-up of 28.2 months, the final analysis grouped together all the personalized treatment cohorts and all cohorts receiving standard chemotherapy. The analysis showed a median overall survival of 96.4 months in the tailored arm and 83.5 months in the control arm, a non–statistically significant trend favoring the customized arm (95% confidence interval [CI] = 0.55–1.04; HR = 0.76). Median recurrence-free survival was 64.4 months and 41.5 months, respectively (HR = 0.74; P = .615).


  • The phase III ITACA randomized trial in adjuvant NSCLC found no survival benefit for customizing chemotherapy according to mRNA expression of ERCC1 and thymidylate synthase.
  • Patients were randomly assigned to receive standard-of-care platinum-based chemotherapy or treatment based on levels of these molecular factors.
  • Toxicity was reduced, however, in patients receiving tailored treatment.

Dr. Novello noted that at the final analysis, just 46% of the 336 expected events had occurred; therefore, the study was underpowered. Assuming these events had been reached, she added, the hazard ratio would be estimated at 0.76 (95% CI = 0.61–0.94; P = .012).

“More comprehensive and high-throughput diagnostic techniques will be needed to tailor adjuvant chemotherapy, with or without immunotherapy, in completely resected NSCLC…. We strongly hope this result will be useful in designing future adjuvant trials and ongoing adjuvant immunotherapy trials,” Dr. Novello said. 

DISCLOSURE: Dr. Novello has served as a consultant or advisor to Sanofi and has participated in a speakers bureau for AbbVie, Amgen, AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Lilly, MSD, Pfizer, Roche, and Takeda.


1. Novello S, et al: International Tailored Chemotherapy Adjuvant Trial: ITACA trial: Final Results. 2020 World Conference on Lung Cancer. Abstract PS01.04. Presented January 29, 2021.

Related Articles

Expert Point of View: Tetsuya Mitsudomi, MD

Tetsuya Mitsudomi, MD

Tetsuya Mitsudomi, MD

Tetsuya Mitsudomi, MD, Professor at Kindai University in Japan and President of the International Association for the Study of Lung Cancer, commented on the negative results of the phase III randomized ITACA trial of adjuvant therapy customization.

“This trial confirmed ...