First Guideline on NGS Testing in Cancer, From ESMO

Pam Harrison

August 28, 2020

Recommendations on the use of next-generation sequencing (NGS) tests for patients with metastatic cancer have been issued by the European Society for Medical Oncology (ESMO), the first recommendations of their kind to be published by any medical society.

"Until now, there were no recommendations from scientific societies on how to use this technique in daily clinical practice to profile metastatic cancers," Fernanda Mosele, MD, medical oncologist, Gustave Roussy, Villejuif, France, said in a statement.

NGS testing is already used extensively in oncology, particularly in metastatic cancer, she noted. The technology is used to assess the sequence of DNA in genes from a tumor tissue sample. Numerous genes can be quickly sequenced at the same time at relatively low cost. The results provide information on mutations that are present, which in turn helps with deciding which treatments to use, including drugs targeting the identified mutations.

"Our intent is that they will unify decision-making about how NGS should be used for patients with metastatic cancer," Mosele said.

The recommendations were published online August 25 in the Annals of Oncology.

Overall, ESMO recommends the use of tumor multigene NGS for non–small cell lung cancer (NSCLC), prostate cancer, ovarian cancers, and cholangiocarcinoma.

For other cancers, the authors say that NGS is not recommended in clinical practice but could be used for research purposes.

However, patients should be informed that it is unlikely that test results would benefit them much personally.

Physicians and patients may decide together to subject the tumor to mutational testing using a large panel of genes, provided testing doesn't burden the healthcare system with additional costs.

"This recommendation acknowledges that a small number of patients could benefit from a drug because they have a rare mutation," Joaquin Mateo, MD, chair of the ESMO working group, said in a statement.

"So beyond the cancers in which everyone should receive NGS, there is room for physicians and patients to discuss the pros and cons of ordering these tests," he added

ESMO also does not recommend the use of off-label drugs matched to any genomic alteration detected by NGS unless an access program and a decisional procedure have been developed, either regionally or nationally.

No Need for NGS Testing of Other Cancers

In contrast to NSCLC, "there is currently no need to perform tumor multigene NGS for patients with mBC [metastatic breast cancer] in the context of daily practice," ESMO states.

This is largely because somatic sequencing cannot fully substitute germline testing for BRCA status, and other mutations, such as HER2, can be detected using immunohistochemistry (IHC).

The same can be said for patients with metastatic gastric cancer, inasmuch as detection of alterations can and should be done using cheaper testing methods, ESMO points out.

However, ESMO members still emphasize that it's important to include patients with metastatic breast cancer in molecular screening programs as well as in clinical trials testing targeted, matched genomic alterations.

Similarly, there is no need to test metastatic colorectal cancer (mCRC) using multigene NGS in daily practice, inasmuch as most level 1 alterations in mCRC can be determined by IHC or PCR.

However, NGS can be considered as an alternative to PCR-based tests in mCRC, provided NGS is not associated with additional cost.

ESMO again recommends that research centers include mCRC patients in molecular screening programs in order for them to have access to innovative clinical trial agents.

As for advanced prostate cancer, ESMO does recommend that clinicians perform NGS on tissue samples to assess the tumor's mutational status, at least for the presence of BRCA1 and BRCA2 mutations, when patients have access to the poly-ADP ribose polymerase (PARP) inhibitors for treatment.

The authors caution, however, that this strategy is unlikely to be cost-effective, so larger panels should be used only when there are specific agreements with payers.

Multigene NGS is also not recommended for patients with advanced pancreatic ductal adenocarcinoma (PDAC), although ESMO points out that it is the role of research centers to propose multigene sequencing for these patients in the context of molecular screening programs.

This is again to facilitate access to innovative drugs for these patients.

Similar to recommendations for patients with advanced PDAC, patients with advanced hepatocellular carcinoma (HCC) do not need to have tumor multigene NGS either.

Considering the high unmet needs of HCC patients, ESMO feels that research centers should propose multigene sequencing to patients with advanced HCC in the context of molecular screening programs.

In contrast, ESMO does recommend that tumor multigene NGS be used to detect actionable alterations in patients with advanced cholangiocarcinoma.

Again, they predict that this strategy is unlikely to be cost-effective, so larger panels should only be used if a specific agreement is in place with payers.

ESMO also assessed the frequency of level 1 alterations in less frequent tumor types, including ovarian cancers. Because BRCA1 and BRCA2 somatic mutations in ovarian tumors have been associated with increased response to the PARP inhibitors, the use of multigene NGS is justified with this malignancy, ESMO states.

The authors also recommend that tumor mutational burden be determined in cervical cancer, moderately differentiated neuroendocrine tumors, salivary cancers, vulvar cancer, and thyroid cancers.

Mosele has disclosed no relevant financial relationships. Many coauthors have relationships with the pharmaceutical industry, as listed in the article.

Ann Oncol. Published online August 25, 2020. Fuill text

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