Standing ovation during the largest oncology congress. “This research will change the standard of treatment”

Katarzyna Pinkosz, Wprost: Lung cancer is the cancer whose treatment has seen the greatest breakthrough in recent years, with the greatest number of new therapies appearing. Were there any new breakthroughs – and new hopes for patients with this cancer – visible at the American Society of Clinical Oncology (ASCO) 2024 Congress?

Prof. Dariusz M. Kowalski: I must admit that so much is changing in the treatment of lung cancer that… it is difficult to understand even for us who deal with lung and chest cancer on a daily basis!

The fact that this is a cancer in which so much is changing is evidenced by the fact that during the plenary session of the ASCO congress – during which truly groundbreaking reports on new methods are presented – out of 5 presentations, as many as 2 concerned the treatment of lung cancer.

One of these presentations concerned the use of a targeted drug, osimertinib, already well known in the treatment of lung cancer?

These were the results of the LAURA study. It involved patients with non-squamous cell carcinoma, i.e. mainly adenocarcinoma, in the third advanced stage: 3A, 3B or 3C, but 50 percent patients qualified for the study had stage 3B. These were patients who did not have distant metastases and were not eligible for surgery; they could be offered radical treatment with radiochemotherapy. The condition for qualifying for sheep was the presence of an activating mutation in the EGFR gene; or rather, the two most common changes: deletion 19 or substitution in exon 21. They received radiochemotherapy (90% of them received simultaneous radiochemotherapy, i.e. it was the optimal treatment), and then were randomly assigned to two groups, one of which received osimertinib and the second placebo.

The difference was spectacular: almost 40 months of progression-free survival for patients receiving osimertinib, compared to 5.6 months for placebo: almost an 8-fold increase in progression-free survival! The presentation of this study was interrupted several times by applause, and at the end there was a standing ovation. This treatment is a huge breakthrough.

Osimertinib is a third-generation tyrosine kinase inhibitor of the EGFR pathway. It is worth emphasizing that it is very well tolerated; The most frequently reported side effects were rashes, skin lesions, and diarrhea, usually of grade 1 or 2 severity.

How far do these patients receive radiochemotherapy in Poland?

Yes. The drug program after treatment with simultaneous radiochemotherapy does not require determination of the EGFR gene status, so some patients may undergo radiochemotherapy and later receive durvalumab, although we know that patients with a mutation in the EGFR gene do not benefit from immunotherapy.

Does this mean that it is also necessary to perform diagnostic tests already at this stage of the disease?

This means that molecular diagnostics are necessary at increasingly earlier stages. Osimertinib was once used in patients with advanced lung cancer and a mutation in the EGFR gene after the failure of first- and second-generation inhibitors when a resistance mutation appeared. Then it was used in the first line as the drug of choice, and for several months we can also use it as a complementary treatment after surgery (according to the results of the ADAURA study).

Now we know that molecular tests also need to be performed in stage 3, because if a patient has a mutation in the EGFRRF gene, he or she should not receive durvalumab as adjuvant treatment, only osimertinib. Of course, the study was presented during the ASCO congress and there is already a publication on this topic, but we still have to wait for American and European registration. There will definitely be this registration.

When it comes to molecular diagnostics, it should soon become standard to perform all molecular tests at the time of diagnosis of adenocarcinoma.

The second breakthrough research result presented at ASCO concerned small cell carcinoma. Is it extremely difficult to treat?

It was a study with the acronym ADRIATIC – it concerned radical treatment of patients with small cell lung cancer. Small cell lung cancer accounts for approximately 20%. all lung cancers, of which 80 percent are recognized already at the seeding stage. Only 20 percent patients have locally advanced disease, without distant metastases. These patients may be offered radical treatment, which is radiochemotherapy. In the ADRIATIC study, patients received radiochemotherapy and then were randomly assigned to adjuvant treatment – for 3 years they received either durvalumab, an anti-PDL-1 antibody, or placebo. When it comes to overall survival, the difference is very large: it is even a doubling of the median: from 33 months to 60 months, which is a huge success in small cell cancer. Two-year survival rates increased from 48 to 57 percent. Importantly, the drug was well tolerated.

It is worth remembering that in the case of small cell carcinoma, virtually no new drugs have appeared for many years. The results of the ADRIATIC study are a huge breakthrough, although of course now we have to wait for registration for this indication.

These are the two most important studies presented at ASCO regarding lung cancer?

It is also worth mentioning the study regarding the results of 5-year follow-up from the CROWN study, conducted in patients with ALK gene rearrangement receiving lorlatinib (third-generation inhibitor) in the first-line treatment compared to the group receiving the first-generation inhibitor (crizotinib). It turned out that after 5 years of treatment, 60 percent patients taking lorlatinib still have no disease progression: these are amazing results. Moreover, the drug reduces the risk of metastases to the central nervous system by over 90%, and patients with a rearrangement in the ALK gene have a predilection for the development of these metastases. This treatment is already available in Poland, but this is the first time that the results of long-term observations have been shown.

Looking at the results of these studies, can we be optimistic that lung cancer will be treated chronically in an increasing number of patients?

In many cases, it is already a cancer that is treated chronically, and now there are opportunities for other groups. There is also a visible tendency that new drugs are used in wider and wider populations, entering the radical treatment segment, increasing the chances of curing patients.