Lung cancer: April reimbursement list with important changes for patients

Lung cancer remains one of the most serious oncological challenges. Non-small cell lung cancer (NDRP) accounts for about 85 percent of all diagnoses of this cancer in Poland. In 10-15 percent of NDRP patients, mutations - called pathogenic variants - are found in the EGFR gene, which encodes the receptor for epidermal growth factor. The disease is more common in women and non-smokers and often develops at a younger age. Detection of EGFR mutations is both diagnostic and therapeutic information: it opens the way to molecularly targeted treatment, much more effective than standard chemotherapy.

It is for this group of patients that the key reimbursement decisions of April this year are intended. Prominent among the new therapeutic options is amivantamab, a bispecific antibody that simultaneously targets two receptors, EGFR and MET. This is a drug from a new, breakthrough therapeutic class, whose mechanism of action allows it to simultaneously block the two signaling pathways that drive tumor growth. The result is greater treatment efficacy and, crucially for patients, a delay in the buildup of resistance to treatment, which is one of the main problems in treating lung cancer with EGFR mutations.

What are bispecific antibodies and why is this a new chapter in oncology?

For years, the standard of care for EGFR-positive non-small cell lung cancer was tyrosine kinase inhibitors - drugs that block signaling through the EGFR receptor. Subsequent generations of these drugs produced better and better results, but inevitably encountered the same problem: the tumor mutated, triggered alternative growth pathways and became resistant to treatment. Bispecific antibodies represent a completely different approach. Amivantamab binds simultaneously to two receptors - EGFR and MET - blocking both pathways that cancer cells can use to escape therapy. The mechanism of action involves both direct blockade of cell signaling and activation of the immune response - amivantamab engages immune cells to destroy cancer cells. This is a multi-directional approach that is more difficult for an evolving cancer to circumvent. Amivantamab made it to the reimbursement list in two clinical indications.

Exon 20. EGFR patients so far without an effective treatment option

The first indication is for patients with activating insertional mutations in exon 20 of the EGFR gene. Amivantamab is used here as first-line treatment, in combination with carboplatin and pemetrexed. This is a rare pathogenic variant - accounting for a few percent of all EGFR mutations, but clinically extremely challenging. The efficacy of standard chemotherapy was unsatisfactory, and the time to disease progression was short. The reimbursement of amivantamab in this indication is a response to a real, hitherto unmet medical need. For the first time, patients with exon 20 insertions are receiving a dedicated, more effective therapeutic option from the first line of treatment.

EGFR exons 19 and 21 - new weapons against resistance

The second indication includes a much larger group: patients with deletions in exon 19 or a p.L858R substitution in exon 21 of the EGFR gene - these are the most common EGFR mutations in non-small cell lung cancer. Amivantamab is used here in combination with lazertinib as first-line treatment. This reimbursement decision addresses one of the most important clinical problems in this group of patients: increasing resistance to third-generation inhibitors, including that associated with activation of the MET pathway. The combination of amivantamab with lazertinib simultaneously blocks both EGFR and MET, the two main mechanisms by which cancer can escape therapy. Clinical trials have shown that this combination brings patients a longer time without disease progression compared to the standard used so far.

More good news from the April list

Amivantamab is not the only good news for lung cancer patients on the new reimbursement list. The list includes atezolizumab for patients with non-small cell lung cancer who have multiple comorbidities and cannot be treated with standard therapy - even platinum compound-based chemotherapy. This is a very large and until now often overlooked group of patients. A new therapeutic option has also been given to patients with small cell lung cancer - a cancer with an extremely poor prognosis and historically few available treatments. Serplulimab, a new immune drug, appeared on the list as a response to the needs of this most difficult group of patients. Patients with the V600E mutation in the BRAF gene - another rare but clinically important pathogenic variant for which clinical trials have so far been the only option - also received reimbursement.

Patient's voice: "Now they can have another years of life ahead of them again."

Margaret Maksymowicz has been suffering from lung cancer for more than a decade. She runs a support group for patients with this cancer on Facebook - a space where patients seeking information, support and understanding meet every day. - Compared to the previous one, the April reimbursement list is, in my opinion, a very good list. It includes new therapeutic options for previously neglected groups of patients," says Malgorzata Maksymowicz. Of all the changes, she singles out several that she considers particularly groundbreaking. One of them relates directly to amivantamab for patients with a mutation in exon 20 of the EGFR gene: - This is just a novelty, a new indication reimbursed for those people who so far have not had this treatment, and this mutation unfortunately has a bad prognosis, she stresses.

He views the second use of amivantamab, for the largest group of patients with EGFR mutations, as a lifeline for patients whose existing treatments are starting to fail: - Now they may again have another years of life ahead of them. This drug gives them a chance to wait until the next therapeutic option.

M.Maksymowicz also talks about atezolizumab for patients with multiple comorbidities: - This is an option for patients who, until now, most often could hear that: "Well, you know, due to the fact that you have a lot of comorbidities, I actually have nothing left for you". They just didn't have any treatment option.

Diagnostics still limp

Even the best drug programs will not solve all the problems associated with treating lung cancer in Poland. One of the biggest challenges remains late diagnosis. - Many patients do not have a chance to qualify for modern treatment because they are diagnosed too late or the diagnosis takes too long. There is a shortage of pathomorphologists, the material for examination is sometimes taken incorrectly, and the patient loses the possibility of treatment in the meantime. This has been discussed in Poland for years and still not much has changed," stresses Malgorzata Maksymowicz, adding that for many patients, new therapies are like licking ice cream through a glass. They just don't have a chance to get to them," she says bluntly. - Why? Because they are diagnosed too late, diagnosed for too long, not diagnosed at all, diagnosed too late. And this is not changing...