Precision medicine extends long-term survival across cancer types
Matching targeted therapy to genetic alterations in the tumour improved response rate and long-term survival in patients with advanced cancer who underwent molecular profiling compared with patients who were unmatched to therapy, highlighting the role of molecular testing in precision medicine, the IMPACT* study shows.
“It’s been 20 years since the first targeted therapy was introduced. These first ‘precision medicine’ therapies revolutionized cancer care and helped many patients live longer,” said ASCO Expert Dr Catherine Diefenbach, a haematologist-oncologist at the Perlmutter Cancer Center in New York, US.
Among the 1,307 patients with ≥1 genetic change detected in the tumour, patients who were matched to a targeted therapy had significantly longer overall survival (OS) than those who were not matched to a targeted treatment because none was available at the time (median OS, 9.3 vs 7.3 months, hazard ratio [HR], 0.72; p<0.001), over more than 10 years of follow-up. [ASCO 2018, abstract LBA2553]
Progression-free survival (PFS) was also longer in the matched group vs the nonmatched group (median, 4 vs 2.8 months, HR, 0.67; p<0.001).
“This is the first and largest study — with the longest follow-up — to assess the impact of precision medicine approaches on survival across multiple cancer types,” said lead author Dr Apostolia Maria Tsimberidou from The University of Texas MD Anderson Cancer Center in Houston, Texas, US.
“Our findings show that molecular testing of tumours with next-generation sequencing can be used to optimize therapy and should be taken into consideration when selecting therapy for patients with difficult-to-treat cancers,” she added.
The IMPACT study included 3,743 patients with advanced cancer who were referred to the study for prospective molecular testing because their disease had worsened despite standard treatment. Tumours were tested for individual gene mutations during early years of the study, while next-generation sequencing was used for testing multiple genes simultaneously in later years of the study.
Out of the total population, 1,307 patients (median age 57 years, 39 percent) had ≥1 genetic alteration, of which, 711 patients received targeted therapy matched to the genetic change in the tumour and 596 received treatment that was not matched (because no targeted therapy was available at the time). The most common types of cancer were gastrointestinal cancer (24.2 percent), gynaecologic cancer (19.4 percent), breast cancer (13.5 percent), melanoma (11.9 percent), and lung cancer (8.7 percent).
The OS rates started to plateau at 3.2 years, with a consistent survival benefit seen with matched therapy vs nonmatched therapy at 3 years (15 percent vs 7 percent) as well as 10 years (6 percent vs 1 percent).
Patients receiving matched therapy also showed better response rate to treatment, in terms of complete response, partial response, and stable disease for ≥6 months (composite rate, 34.9 percent vs 20.1 percent; p<0.001).
Patient’s baseline characteristics that were independently associated with a shorter OS included genetic changes in the PI3K/AKT/mTOR pathway, elevated lactate dehydrogenase levels, liver metastases, poor functional status, elevated platelet counts, low albumin levels, and age ≥60 years.
“We’ve just scratched the surface. Now with faster and more robust genetic tests, we can help even more patients by treating the cancer based on its genetic makeup rather than solely on its location in the body,” said Diefenbach.
The researchers will continue to look at survival benefits of precision medicine in oncology in the ongoing randomized phase II IMPACT2 trial.