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08-02-2021 | Non-small-cell lung cancer | News

WCLC 2020

ITACA pharmacogenomic adjuvant chemotherapy approach does not boost resected NSCLC outcomes

Lynda Williams

medwireNews: Non-small-cell lung cancer (NSCLC) survival after complete resection was not improved by use of mRNA expression levels of two genes to guide choice of adjuvant chemotherapy, shows research reported at the IASLC 2020 World Conference on Lung Cancer.

Silvia Novello (University of Turin, Italy) reported the ITACA study findings showing no difference in overall survival (OS) or recurrence-free survival (RFS) when patients with stage II–IIIA NSCLC were given adjuvant chemotherapy based on pharmacogenomic analysis or a control regimen consisting of an investigator’s choice of cisplatin-based doublet chemotherapy.

The 773 patients were all assessed for mRNA expression levels of the excision repair cross complementation 1 (ERCC1) and thymidylate synthase (TS) genes and classified as having one of four molecular profiles.

As high levels of ERCC1 mRNA have been linked to resistance to cisplatin, carboplatin, and oxaliplatin, patients with expression above the median value in the tailored treatment arm were not permitted to receive cisplatin, the presenter explained.

By contrast, low TS mRNA has previously been associated with improved response to cisplatin plus pemetrexed in lung adenocarcinoma and therefore patients with mRNA expression below the median for this gene were assigned to receive this combination.

Patients were therefore randomly assigned to receive the regimens as below:

High ERCC1, high TS – paclitaxel alone (n=137) or control (n=127);High ERCC1, low TS – pemetrexed alone (n=35) or control (n=41);Low ERCC1, high TS – cisplatin plus gemcitabine (n=85) or control (n=98);Low ERCC1, low TS – cisplatin plus pemetrexed (n=87) or control (n=80).

After a median 28.2 months of follow-up, median OS was 96.4 months for patients given a pharmacogenomics-guided adjuvant chemotherapy and 83.5 months for those given the control regimen, but the hazard ratio (HR) for death of 0.76 did not reach statistical significance.

Median RFS was also statistically comparable between these treatment arms, at 64.4 versus 41.5 months and a HR of 0.94.

Novello noted that there was no heterogeneity in the OS between the four molecular profile groups, and that there were no patient subgroups who derived a significant OS or RFS benefit from receipt of a pharmacogenomics-guided regimen over the control regimen.

However, she remarked that as just 46% of the expected OS events had occurred during follow-up, the study was “underpowered,” and that if the same HR had been found for all 336 of the expected OS events, the 95% confidence interval would be 0.61–0.94, giving a significant p value of 0.012.

The presenter also reported that patients who received a tailored regimen were significantly less likely than controls to develop a grade 3 or 4 adverse event.

One or more events at this severity occurred in 32.6% and 45.9% of the groups, respectively, giving an odds ratio of 0.57, and indicating that customizing treatment offered a “significantly improved toxicity profile without compromising the activity,” she said.

“More comprehensive and high-throughput diagnostic techniques will be needed in order to tailor adjuvant chemotherapy (with or without immunotherapy) in completed resected NSCLC,” Novello concluded.

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2021 Springer Healthcare Ltd, part of the Springer Nature Group

IASLC 2020 World Conference on Lung Cancer; 28–31 January 2021

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