However, side effects management will be a key issue due to its combined use with new drugs.

Rybrevant is an intravenous (IV) formulation that requires dosing once every three weeks.

Adding an IV formulation to the existing oral formulation, Leclaza, could double the effectiveness but reduce dosing convenience.

Janssen is also developing a subcutaneous (SC) formulation to significantly reduce dosing time and address concerns about infusion-related side effects.

Recently published clinical results showed that the combination of the subcutaneous formulation of Rybrevant SC+Leclaza achieved similar outcomes to Rybrevant IV+Leclaza.

At a median follow-up period of 7 months, the Leclaza+Rybrevant SC was non-inferior to Leclaza+Rybrevant IV.

“The Leclaza+Rybrevant combination therapy has continued to generate positive data in brain metastases, L858R mutation, etc., and therefore can be a viable first-line treatment option for EGFR-mutated NSCLC,” said a professor of medical oncology at a university hospital.

”It is difficult to say that use of the combination therapy is good for all patients, as the use of combination therapy is associated with more side effects than using either drug as monotherapy.

This is why prescribing Rybrevantto to older patients can be challenging.” “The use of the intravenous formulation of Rybrevantrequires much attention.

While a subcutaneous formulation is currently in development, the existing intravenous formulation is associated with frequent rashes, paronychia, and infusion-related adverse events.

When selecting a treatment, we should consider not just the efficacy but the patient's overall experience, including side effects, frequency of visits, and quality of life.

So there will be an active debate about which patients will benefit most from the early use of the combination therapy.” Concerns also rise on the lack of later-line therapies following the use of Tagrisso+platinum-based chemotherapy The use of Tagrisso and platinum-based chemotherapy as first-line treatment may lead to a shortage of treatment options for patients who develop resistance.

In the past, EGFR-mutated NSCLC targeted therapies have been used as follows: 3rd generation TKIs were used on patients who were confirmed to be T790M-positive during biopsy after using 1st and 2nd generation TKIs, and platinum-based chemotherapy (Alimta plus carboplatin/cisplatin) was used on T790M-negative patients.

So if a 3rd-generation TKI monotherapy is used in the first line, platinum-based chemotherapy is often used as a second-line treatment as they cannot use 1st or 2nd-generation TKIs due to resistance.

This suggests that the use of both Tagrisso and platinum-based chemotherapy in the first line may lead to a lack of later-line treatment options.

After developing a resistance to the combination, only taxane drugs such as docetaxel and paclitaxel and immuno-oncology drugs targeting PD-L1 will remain as treatment options.

“After failing treatment with EGFR-TKIs, we usually use platinum-based chemotherapy, Alimta+cisplatin/carboplatin,” says a professor of medical oncology at a university hospital.

“Combining these drugs with 3rd-generation TKIs is certainly therapeutic.

However, we should also consider the lack of later-line treatment options after the patient develops TKI resistance if we pull the next line of treatment in advance amid a shortage of treatment options.” “As 3rd-generation TKIs have settled as the first-line standard of care, the role of 1st- and 2nd-generation TKIs will continue to diminish, and it is likely that it will ultimately become a competition between 3rd-generation TKI monotherapy and combination therapy.”