Key messages

People with advanced cancers who received matched targeted therapies, either alone or in combination with standard treatments, experienced longer periods of disease control compared to those receiving standard treatments alone. However, the evidence on whether these therapies extend overall survival remains inconsistent. Further information is needed on the potential harms of matched targeted therapy and whether it improves the overall quality of life.

Early genetic testing using next-generation sequencing is recommended for individuals with advanced cancers to help guide treatment with matched targeted therapies. While these therapies can be highly effective, it is crucial to carefully manage potential side effects and prioritise the individual’s overall wellbeing when making treatment decisions.

What do we already know?

Matched targeted therapies given alone or in combination with chemotherapy or hormonal therapies have delivered proven survival benefits for many people with newly diagnosed cancers. However, there is little evidence of their effectiveness in the recurrent or advanced setting. Therefore, next-generation sequencing testing for recurrent or late stage disease is not routinely conducted in those people whose cancer has progressed through at least one line of standard anti-cancer treatment.

What is next-generation sequencing?

Next-generation sequencing of cancer identifies specific mutations in the DNA of a person’s cancer cells. These mutations can give clinicians clues about why the cancer is growing and which treatments might work best. This helps choose "targeted therapies" designed to attack those specific mutations, making treatment more personalised and potentially more effective.

What did we want to find out?

The purpose of this review was to find out whether people with advanced cancers given matched targeted therapies based on mutations identified from next-generation sequencing testing benefited these people more than those people who received non-matched chemotherapy or hormonal therapy.

What did we do?

We searched for studies that investigated any matched targeted therapies compared to people who received standard chemotherapy or hormonal therapy or no treatment. Only adults older than 18 years were included in the review. We compared and summarised the results of the studies and rated our confidence in the evidence, based on factors such as study methods and sizes.

What did we find?

We found 37 studies with nearly 10,000 people with advanced cancers that had either received matched targeted therapies or standard anti-cancer treatment or no treatment. We found the following:

1. Matched targeted therapies vs. standard treatment:

Matched targeted therapies probably delay cancer progression more effectively than standard-of-care treatments. However, it is still unclear whether targeted therapies also prolong the individual's life. They may also increase the overall response rate, but it was unclear whether the incidence of potential harms would increase with matched targeted therapy. There was not enough information about the benefits of matched targeted therapy on quality of life, as very few studies reported it.

2. Matched targeted therapies in combination with standard treatment vs standard treatment alone:

Combining matched targeted therapies with standard-of-care treatment probably delays the risk of cancer progression and also probably prolongs the individual's life. The combination may also increase the overall response rate. However, there was no clear evidence of the potential harm of combination treatment and its overall impact on quality of life.

3. Matched targeted therapies vs. non-matched targeted therapy:

Matched targeted therapies probably have more benefits than targeted therapies not based on genetic matching in delaying cancer progression and prolonging the individual's life. However, there was no clear evidence of their impact on overall response rate and potential harms. No studies looked at whether the matched targeted therapy impacted the overall quality of life in this setting.

4. Matched targeted therapies vs. no active treatment (best supportive care):

Matched targeted therapies probably delay cancer progression compared to no active treatment. It is unclear if matched targeted therapies prolong the individual's life. There was limited evidence of the impact of matched targeted therapy on overall response rates, potential harms and its impact on overall quality of life.

Summary of findings

Matched targeted therapies can probably delay cancer progression, but there is some evidence to suggest that they help people live longer or improve their overall quality of life. Early access to genetic testing for people with advanced cancers could help identify treatment options and improve care. This review supports making genetic testing more available for people with advanced cancers.

What are the limitations of the evidence?

The certainty of evidence across the comparisons was moderate-certainty for progression-free survival, moderate to low-certainty for overall survival and low to very low-certainty for overall response rate, adverse events and quality of life, respectively. We have found limited evidence of the impact of matched targeted therapies on quality of life, as very few trials reported this outcome, which is an important outcome for determining the overall benefit of the drug.

How up-to-date is the evidence?
The review authors searched for studies that had been published up to October 2024.