Identification of molecular aberrations paved the way towards target therapy (TT) [5] discovery and wide use. At present, there are at least, 9 molecular markers with the number still counting.

Osimertinib is currently the most widely TT utilized. It is used as neoadjuvant, adjuvant and in advanced/metastatic lung cancer [6]. Osimertinib plus chemotherapy was recently reported to significantly prolongs the overall survival in EGFR-mutated in a/d-NSCLC [7].

Except for Ivonescimab [8-10], all the drugs analyzed in our study are approved and utilized in the United States (US), European nations and Canada.

In Table 1, costs of ICIs, Glucagon like peptides (GLP-1) and Evolocumab were compared with the proposed 9-month $188,000 cost of Ivonescimab [8-10].

Target Therapy Costs

Almost all TT listed drugs were approved after 2-3-year testing. Hence, their 2-3 years use was the norm rather than the exception (Table 2).

DISCUSSION

Pembro discovery paved the way to 4 more ICI introduction, each with similar and/or additional therapeutic triumph over disease. Ivonescimab, of the Bispecific class, was later discovered and approved in China. Its prolongation of disease-free survival at proposed 9- months $188,000 was indeed worthy and justified [8-10].

The ICI costs are, in general, relatively high. Pembro, the 1^st ICI member discovered, has over 15 approved indications in early and later-stage cancers. It has paved the way to other ICI discovery but with lesser number of indications. The Impact and duration of use of ICI and TT on cost in lung cancer has been previously discussed [5]. Costs have since changed and some drugs have become generics.

TT family members are similarly expensive. The low incidence of targetable markers essentially rationalizes their relatively high costs. Ret fusion was extensively studied. Its prevalence in NSCLC is 1-2% but relatively higher in papillary thyroid and salivary gland cancer.

The incidence of EGFR in lung cancer is associated with adenocarcinoma histology and increases with smoking. It is 15% in the US, 10-15% and Europe, and 40% in Asia. In California, Orange County US, EGFR incidence is 20% compared with 15% in Los Angeles (LA), approximately 20 miles apart. The LA area has a higher number and percentage of smokers.

Over the last 10 years since our 1^st publication 2015 [5] on approaches to control drug costs e.g. imposing caps and/or 37.5% cost reduction have been suggested [6]. To lessen the impact of the drug heavy financial burden [11-13], it has become clear over the last few years that the best cost-cutting approach would entail direct face to face negotiation between government and pharma.

In summary, the wide variation in drug costs could in part reflect on the number of potential eligible patients. The total duration of therapy is costly and needs to be scrutinized, if not limited. Future drugs need to be effective, safe and if possible, with well-defined and controlled treatment duration.

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  Table 1
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  Table 2