Cancer continues to be one of the leading causes of morbidity and mortality in the world.
It is estimated that in the year 2020, approximately 18.1 million new cases of cancer in
the world, and that this figure will increase in the next two decades to 27 million. The
most frequently diagnosed tumors in the world in 2020 were those of the breast, lung
(which occupies the second position), colon and rectum, prostate and stomach, all of them
with more than one million cases.
Also, in Spain, cancer is one of the main causes of morbidity and mortality. It is
estimated that in 2020 there were 113,054 deaths from cancer in Spain. The number of
cancers diagnosed in Spain in 2022 is estimated to reach 280,100 cases according to
REDECAN calculations, which represents a slight increase compared to previous years. Lung
cancer (LC) is the tumor responsible for the highest mortality worldwide. After prostate
cancer, it is the second most common cancer in men and, after breast cancer, in women.
Lung adenocarcinoma is the major subtype of lung cancer and represents the deadliest
human cancer, affecting current-, ex-, and even non-smokers.
The most frequently diagnosed cancers in Spain in 2023 will be those of the colon and
rectum, breast, lung, prostate, and urinary bladder. Lung cancer is a very common cancer
in Spain, however, due to its high mortality, its prevalence at five years is relatively
low.
Approximately 30% of patients with non-small cell lung cancer (NSCLC) have early-stage
disease that is treated with surgery. A high percentage of these patients relapse and
die, so patients receive postoperative adjuvant systemic chemotherapy to increase their
survival. However, the benefits of this strategy are modest. NSCLC is often associated
with druggable molecular alterations that drive lung carcinogenesis. EGFR tyrosine kinase
inhibitors (TKIs) have been included in treatment paradigms with the aim of improving the
outcome of adjuvant therapy in patients with completely resected, EGFR mutation-positive
(EGFRm+) disease.
Osimertinib is indicated as monotherapy for the first-line treatment of adult patients
with locally advanced or metastatic non-small cell lung cancer (NSCLC) with activating
mutations in the epidermal growth factor receptor (EGFR), for the treatment of adult
patients with EGFR T790M mutation-positive locally advanced or metastatic NSCLC, for the
adjuvant treatment of adult patients with NSCLC stages IB-IIIA after complete resection
of the tumor that has activating mutations of the EGFR (exon 19 deletion or exon 21
substitution (L858R)), for the treatment of adult patients with locally advanced,
unresectable NSCLC whose tumours have EGFR exon 19 deletions or exon 21 (L858R)
substitution mutations and whose disease has not progressed during or following
platinum-based chemoradiation therapy, and in combination with pemetrexed and
platinum-based chemotherapy for the first-line treatment of adult patients with advanced
NSCLC whose tumours have EGFR exon 19 deletions or exon 21 (L858R) substitution
mutations.
The FLAURA trial showed that treatment with osimertinib significantly prolongs
progression-free survival (PFS) compared to EGFR TKI comparator (median 18.9 months and
10.2 months, respectively, HR=0.46, 95% CI: 0.37, 0.57; P<0.0001) (5) and improves
overall survival (OS) (HR=0.799 [95.05% CI: 0.641, 0.997]) compared to standard EGFR
tyrosine kinase inhibitors (TKIs), in patients with EGFR mutation-positive advanced
non-small-cell lung cancer (NSCLC). A greater proportion of patients treated with
osimertinib were alive at 12, 18, 24 and 36 months (89%, 81%, 74% and 54% respectively)
compared to patients treated with EGFR TKI comparator (83%, 71%, 59% and 44%
respectively).
The results of the ADAURA trial showed that adjuvant treatment with osimertinib reduced
the risk of recurrence or death by 83% in stages II to IIIA, and in 80% in stages
IB-IIIA, compared with placebo, in patients with NSCLC with completely resected stage IB
to IIIA disease and confirmed EGFR mutation. Additionally, osimertinib demonstrated a
highly statistically significant improvement in disease free survival (DFS) and HRQoL was
maintained. A DFS benefit favouring osimertinib over placebo was seen across all
prespecified subgroups, including those based on disease stage, EGFR sensitizing
mutation, ethnicity and receipt of adjuvant chemotherapy. Furthermore, the DFS benefit
with osimertinib was similar in patients who had or had not received chemotherapy.
The FLAURA2 trial showed that first-line treatment with osimertinib-chemotherapy led to
significantly longer progression-free survival than osimertinib monotherapy among
patients with EGFR mutated advanced NSCLC . Investigator-assessed progression-free
survival was significantly longer in the osimertinib-chemotherapy group than in the
osimertinib group (hazard ratio for disease progression or death, 0.62; 95% confidence
interval [CI], 0.49 to 0.79; P<0.001). At 24 months, 57% (95% CI, 50 to 63) of the
patients in the osimertinib- chemotherapy group and 41% (95% CI, 35 to 47) of those in
the osimertinib group were alive and progression-free. An objective response was observed
in 83% of the patients in the osimertinib-chemotherapy group and in 76% of those in the
osimertinib group; the median response duration was 24.0 months (95% CI, 20.9 to 27.8)
and 15.3 months (95% CI, 12.7 to 19.4), respectively. The safety profile of osimertinib
plus pemetrexed and a platinum-based agent was consistent with the established profiles
of the individual agents.
The LAURA trial showed that treatment with osimertinib after chemoradiotherapy resulted
in significantly longer progression-free survival than placebo among patients with
unresectable stage III EGFR-mutated NSCLC. Osimertinib offered a median PFS of 39.1
months, compared with only 5.6 months with placebo (HR 0.16, 95% CI [0.10, 0.24];
P<0.0001). The percentage of patients who were alive and progression free at 12 months
was 74% (95% CI, 65 to 80) with osimertinib and 22% (95% CI, 13 to 32) with placebo. The
overall safety profile of osimertinib after chemoradiotherapy was consistent with the
established profile of osimertinib and chemoradiotherapy.
