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 » Introduction
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  Table of Contents  
Year : 2022  |  Volume : 59  |  Issue : 5  |  Page : 1-10

Safety of osimertinib in adult patients with metastatic epidermal growth factor receptor T790M mutation-positive non-small cell lung cancer: Results from a Phase IV study in India

1 Department of Medical Oncology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India
2 Department of Medical Oncology, Tata Memorial Hospital, Dr. Ernest Borges road, Parel, Mumbai, Maharashtra, India
3 Department of Medical Oncology, Tata Medical Center, New town, Rajarhat, Kolkata, West Bengal, India
4 Department of Medical Oncology, Apollo Cancer Institute, Jubilee Hills, Hyderabad, Telangana, India
5 Department of Medical Oncology, Basavatarakam Indo-American Cancer Hospital, Banjara Hills, Hyderabad, Telangana, India
6 Department of Medical Oncology, Kokilaben Dhirubhai Ambani Hospital and Medical Research Institute, Andheri (W), Mumbai, Maharashtra, India
7 Department of Medical Oncology, Rajiv Gandhi Cancer Institute Research Centre, Rohini, New Delhi, India

Date of Submission19-Nov-2020
Date of Acceptance16-Feb-2022
Date of Web Publication24-Mar-2022

Correspondence Address:
Prabhat S Malik
Department of Medical Oncology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijc.ijc_1374_21

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 » Abstract 

Background: A Phase IV, single-arm study was conducted to assess the safety of osimertinib in Indian patients with epidermal growth factor receptor (EGFR) T790M mutation-positive stage IV non-small cell lung cancer (NSCLC).
Methods: Enrolled patients received 80 mg osimertinib for six cycles or until disease progression or unacceptable toxicity or withdrawal. Primary safety variables included treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and adverse events (AEs) leading to discontinuation/interruption/change (D/I/C) of drug dose, and AEs of special interest (AESIs). AEs were summarized by the percentage of patients experiencing at least one occurrence of each event.
Results: Of the 60 enrolled patients (median age 58 [range: 34–81] years; 51.7% women) at eight sites, nine patients were discontinued prematurely due to disease progression (n = 7) and death (n = 2); median (range) duration of treatment was 126 (1–134) days. Median age of patients was 58 (34–81) years; 51.7% (n = 31) were women; 86.7% (n = 52) were nonsmokers; and most of them (98.3%) had adenocarcinoma. About 75% (n = 45) of patients experienced any of the TEAEs, with the most frequent being fatigue and creatine phosphokinase (CPK) increase (n = 6, 10% each). TEAEs in 11 (18.3%) patients were judged as study treatment related, with CPK increase being the most common (n = 4, 6.7%). TEAEs led to D/I/C of drug dose in eight (13.3%) patients, with one being study treatment related. Nine (15%) patients had AESIs of dyspnea (n = 6), chest pain (n = 2), and cardiorespiratory arrest (n = 1); two of them had a fatal outcome. One AESI (mild dyspnea) was considered study drug related. TEAEs of grade ≥3 were reported in seven (11.7%) patients, including dyspnea in two (3.3%), followed by diarrhea, mucosal inflammation, cardiorespiratory arrest, and others (n = 1, 1.7% each). None of the SAEs and fatal events were considered as study treatment related. Seven (11.7%) patients had abnormal electrocardiogram (ECG; not clinically significant) at the end of the study.
Conclusion: Our study confirms the favorable safety profile of osimertinib without any new safety concerns in Indian patients with EGFR T790M mutation-positive stage IV NSCLC. Identifier: NCT03853551
CTRI registration no. CTRI/2018/10/015941

Keywords: Epidermal Growth Factor Receptor, non-small cell lung cancer, osimertinib, stage IV NSCLC, tyrosine kinase inhibitor
Key Message This study in Indian patients provides real world evidence of safety profile of osimertinib. No new safety signals were generated and benefit risk profile remained unchanged in Indian patients

How to cite this article:
Malik PS, Noronha V, Dabkara D, Maddu VK, Rajappa S, Limaye S, Batra U. Safety of osimertinib in adult patients with metastatic epidermal growth factor receptor T790M mutation-positive non-small cell lung cancer: Results from a Phase IV study in India. Indian J Cancer 2022;59, Suppl S1:1-10

How to cite this URL:
Malik PS, Noronha V, Dabkara D, Maddu VK, Rajappa S, Limaye S, Batra U. Safety of osimertinib in adult patients with metastatic epidermal growth factor receptor T790M mutation-positive non-small cell lung cancer: Results from a Phase IV study in India. Indian J Cancer [serial online] 2022 [cited 2022 Aug 18];59, Suppl S1:1-10. Available from:

 » Introduction Top

Lung cancer is the leading cause of cancer-related mortality, accounting for 1.79 million cancer-related deaths, and the second leading cause of cancer (2.20 million new cases) worldwide as of 2020.[1] In India, it contributes to 7.8% (66,279) of all cancer deaths and was the second leading cause of cancer in men with 51,675 new cases reported in 2020.[2] About 85% of lung cancers are non-small cell lung cancers (NSCLCs), with adenocarcinoma being the most common form.[3],[4] Mutations in the tyrosine kinase domain of epidermal growth factor receptor (EGFR) are frequently found in patients with adenocarcinoma subtype (moderately differentiated adenocarcinomas 58% vs. poorly differentiated adenocarcinoma 30%; P < 0.001).[5] Approximately 22%–26% patients with NSCLC harbor EGFR mutations in India.[4],[6] Similar to the global trend, one of the major challenges for optimum management of lung cancer in India is delayed diagnosis – the majority of patients are diagnosed with distant metastasis (men, 44.0% and women, 47.6%).[7]

Until 2018, first- and second-generation tyrosine kinase inhibitors (TKIs) such as gefitinib, erlotinib, and afatinib were considered the standard treatment for patients with EGFR-mutated NSCLC. Despite the high initial tumor response rates with EGFR-TKIs, patients often exhibit disease progression after 9–13 months of treatment.[8] The acquisition of EGFR T790M mutation is the common resistance mechanism, which inhibits the binding of EGFR-TKIs to the adenosine triphosphate (ATP)-binding site of EGFR.[4],[9],[10] The EGFR T790M mutations account for 50% of disease progression after treatment with EGFR-TKIs.[11],[12],[13],[14]

Osimertinib is a third-generation EGFR-sensitizing (exon 19 and L858R) and T790M-resistant mutants that spares wild-type EGFR.[15] The primary analysis of AURA 3 trial (data cutoff: April 15, 2016) demonstrated better progression-free survival (PFS, 10.1 months) with osimertinib compared with platinum chemotherapy (4.4 months) (hazard ratio [HR] 0.30, 95% confidence interval [CI] 0.23–0.41, P < 0.001) in adult patients with centrally confirmed EGFR T790M-positive locally advanced/metastatic NSCLC and radiological evidence of progression following treatment with a first-line EGFR-TKI.[16] Based on these results, osimertinib was recommended[17] and approved by the United States Food and Drug Administration (2020),[18] European Commission (2018),[19] and Central Drugs Standard Control Organization, India (2018)[20] for treatment in adult patients with confirmed EGFR T790M-positive locally advanced/metastatic NSCLC and radiological evidence of progression following treatment with a first-line EGFR-TKI. Mature data of AURA 3 trial (data cutoff: March 15, 2019) showed a numerical benefit of overall survival (OS) median OS was 26.8 months in osimertinib arm (95% CI 23.5–31.5)vs. 22.5 months (95% CI 20.2– 28.8) in comparator arm for osimertinib over platinum–pemetrexed.[21]

The safety profile of osimertinib is well established in clinical evaluations such as the Phase I AURA study,[22] Phase II extension of AURA,[23] and AURA 2 study.[24] Osimertinib is expected to have milder toxicities compared with first- and second-generation TKIs because of its ability to spare wild-type EGFR,[15] which is evident from cross-trial comparisons by Bollinger et al.[25] A pooled analysis of AURA extension and AURA 2 study reported the most common grade ≥3 possibly causally related adverse events (AEs) as diarrhea (3 9%; <1%) and rash (grouped terms; 42%; grade ≥3, 1%). Fatal AEs (interstitial lung disease [ILD], n=3 and pneumonitis, n=1) reported in 4 (1%) patients were possibly causally related to osimertinib..[26] Similarly, Phase III AURA 3 clinical study demonstrated that osimertinib (n = 279) was generally well tolerated in comparison with pemetrexed plus platinum therapy (n = 140), with a low rate of grade ≥3 AEs and one fatal AE due to ILD.[16] ILD or ILD-like adverse reactions (e.g., pneumonitis) associated with osimertinib in clinical studies is a concern and may need more exploration in routine clinical practice. QT interval prolongation is another AE of concern that was reported in 4% of patients treated with osimertinib, with one event being of grade 3 severity in AURA 3.[16] Several major clinical trials of osimertinib, such as the BLOOM study,[27] FLAURA study,[28] AURA 17 in Asia-Pacific region,[29] and real-world evaluation in Macau and ASTRIS in 17 countries[30],[31] found osimertinib to be well tolerated with manageable AEs without any new safety signals.

In India, the safety of osimertinib has been explored in a very small number of patients in a real-world setting.[32] This Phase IV study was conducted to assess the safety of osimertinib in Indian adult patients with EGFR T790M mutation-positive NSCLC as a postmarketing mandate and to generate evidence of safety on osimertinib in the Indian population.

 » Subjects and Methods Top

Study Design and Population

This Phase IV, prospective, single-arm study was conducted at eight centers across India between April 2019 and April 2020. After obtaining written informed consent from the patients or their legally acceptable representatives, patients eligible to receive osimertinib as per locally approved prescribing information and ratified by an independent clinical judgment of the treating physician were screened. Patients of either gender, ≥18 years of age, with a confirmed diagnosis of metastatic EGFR T790M mutation-positive NSCLC (stage IV as per the American Joint Committee on Cancer [AJCC] staging 8th edition, except for one patient who had stage III NSCLC) by plasma or tissue biopsy on polymerase chain reaction-based platform, and had progressed on or after prior EGFRTKI therapy were included in the study. Pregnant or lactating women and patients with a history of hypersensitivity to either excipients of osimertinib or other TKIs were excluded from the study.

Enrolled patients were treated with a once-daily dose of 80 mg osimertinib tablet for six treatment cycles of 21 days each. The treatment phase of the study was considered as Cycle 1 Day 1 to the end of treatment (EOT), that is, Cycle 6 Day 21, or until study drug discontinuation due to either disease progression, unacceptable toxicity, or other reasons such as consent withdrawal by the patient, whichever occurred first. A telephonic follow-up was conducted 28 days after the EOT visit, which was the end of study (EOS) for each patient. Concomitant use of medications, herbal supplements, and/or ingestion of food that are known to be potent inducers of cytochrome P450 (CYP) 3A4 were prohibited whenever feasible, but any medication that was clinically indicated for the treatment of an AE was allowed.

Outcome Variables

Data on demographic characteristics, relevant medical history, disease characteristics, and cancer treatment history were collected at screening visit. Patients were monitored for the occurrence of AEs and use of concomitant medications during the treatment period until EOS. Safety assessments were done on Day 1 of each cycle, which included hematology and biochemistry tests, 12-lead electrocardiogram (ECG), vital signs, and symptom-directed physical examination. Treatment-emergent AEs (TEAEs) were defined as AEs with onset during the treatment phase or worsening of a pre-existing condition since baseline. The main safety variables evaluated and reported were AEs, serious AEs (SAEs), AEs leading to dose modification/interruption/discontinuation, AEs of special interest (AESIs) such as ILD/pneumonitis-like events, QT prolongation events, and deaths due to AE or unknown cause. AEs were coded by System Organ Class (SOC) and Preferred Term (PT) according to the MedDRA Version 23.0. The intensity of AEs was graded by the National Cancer Institute (NCI) Common Terminology Criteria for AE (CTCAE) Version 4.0 or higher.


The study protocol (NCT03853551; CTRI/2018/10/015941) was approved by the independent ethics committees/institutional review boards of all participating centers. The study was conducted in accordance with the Declaration of Helsinki, International Council for Harmonisation (ICH), good clinical practices (GCP), good pharmacoepidemiology practices (GPP), and the applicable legislation on noninterventional studies and/or observational studies. The reporting has been done in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist.[33]

Statistical Analysis

Based on the prevalence of T790M mutation in adenocarcinoma NSCLC patients who have progression first line EGFR TKI based treatment in firstline setting, a sample size of 60 patients was determined, in order to provide the exact two-sided 95% CI for a list of percentages of patients reporting at least one AE. Safety analysis set (safety population) included all enrolled patients who received at least one dose of study medication during the treatment period. Data were summarized using this population. Descriptive statistics were provided for vital sign parameters (pulse rate, systolic and diastolic blood pressure, and weight) for the observed values and change from baseline at each cycle. All reported AEs were included in the analysis. For each AE, the percentage of patients who experienced at least one occurrence of the given event was summarized; AESIs were summarized separately. QT data were summarized descriptively. The number and percentage of patients with maximum postdose QT value and the maximum increase from baseline were tabulated for each cycle. The World Health Organization (WHO) performance status was summarized with number and percentage for each status per cycle.

 » Results Top

A total of 63 patients were screened for the study to enrol1 60 patients with metastatic EGFR T790M mutation-positive NSCLC. Fifty-one patients (85.0%) of the safety population (n = 60) completed all six cycles of osimertinib treatment. Of the nine (15%) patients who discontinued prematurely from the study, seven had disease progression and two patients died. [Figure 1] depicts the disposition of the patients in the study.
Figure 1: Patient disposition in the study

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Demographic and Baseline Characteristics

The median (range) age of patients was 58 (34–81) years; 31 (51.7%) were women. Most of the patients (n = 52, 86.7%) did not have a history of tobacco exposure. Most of the patients (n = 59, 98.3%) had adenocarcinoma subtype. Approximately two-thirds (n = 39, 65.0%) of patients had received at least one previous cancer therapy regimen (with chemotherapy and/or radiotherapy), of whom 26 patients (43.3%) received prior radiotherapy. At baseline, all enrolled patients had normal activity as assessed by WHO performance status [Table 1].[34]
Table 1: Demographic and baseline characteristics

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Treatment-Emergent AEs

The median (range) duration of treatment was 126 (1–134) days. A total of 47 (78.3%) patients experienced AEs during the study period; 45 (75.0%) patients had at least one TEAE. [Figure 2] shows the percentage of patients with AE types. Three (5%) patients had fatal TEAEs; none were considered treatment related. TEAEs leading to study drug discontinuation, interruption, or dose change of treatment were reported for eight patients (13.3%); it was treatment related in one patient.
Figure 2: Summary of adverse event. AE = adverse event, D/I/C = discontinuation/interruption/change of therapy, TEAEs = treatment-emergent adverse events

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The severity and causality of TEAEs are described in [Table 2].
Table 2: Severity and relatedness of treatment-emergent adverse events (occurred in >1% patients by System Organ Class and Preferred Terms)

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More than 5% patients experienced the following TEAEs: fatigue, creatine phosphokinase (CPK) increase (n = 6, 10% each); decreased appetite, diarrhea, cough, dyspnea, thrombocytopenia (n = 5, 8.3% each); constipation, mucosal inflammation, skin rash, paronychia, pain in extremity (n = 4, 6.7% each); and pyrexia, pruritus, nausea, vomiting, increase in transaminases, anemia (n = 3, 5% each).

TEAEs in 11 (18.3%) patients were judged as related to the study treatment, with blood CPK increase being the most common (n = 4, 6.7%), which was also the reason for discontinuation of the study drug in two (3.3%) patients. Paronychia, dengue, mucosal inflammation, fatigue, diarrhea, lip and tongue pigmentation, dyspnea, thrombocytopenia, deep vein thrombosis, and cardiorespiratory arrest were the other reasons for study drug discontinuation/interruption or change.

SAEs and AESIs

Approximately 15% (9/45) patients had AESIs such as dyspnea (n = 6, 10%), chest pain (n = 2, 3.3%), and cardiorespiratory arrest (n = 1, 1.7%). Two of these nine patients had a fatal outcome: cardiorespiratory arrest (n = 1) and dyspnea (n = 1); one patient had grade 3 serious TEAE (dyspnea). Only one AESI (mild dyspnea) was considered related to the study drug. There was one more fatal event due to disease progression.

TEAEs were grade ≥3 in seven (11.7%) patients, including dyspnea (n = 2, 3.3%), and thrombocytopenia, cardiorespiratory arrest, cataract, diarrhea, mouth ulceration, mucosal inflammation, dengue fever, and deep vein thrombosis (n = 1, 1.7% each).

None of the SAEs and fatal events were considered related to the study drug.

Clinical Laboratory Evaluation

No clinically significant changes in the mean levels from baseline visit to EOT visit were observed for hematology and biochemistry tests. Mean platelet count decreased from baseline visit to EOT visit by 92.9 × 109/L; however, the mean ± standard deviation (SD) baseline (281.0 × 109 ± 101.13/L) and EOT visit (186.1 × 109 ± 78.95/L) platelet counts were within normal limits. Baseline visit to EOT visit showed a mean ± SD increase in CPK by 106.89 ± 111.28 U/L and a decrease in alkaline phosphatase of 52.36 ± 122.16 U/L. Worst post-baseline treatment-emergent reductions from baseline grade to grade ≥3 were observed for hemoglobin, absolute leukocytes, absolute lymphocytes, and absolute neutrophil counts. Calcium levels were raised from baseline grade 0 to grade 4 in two patients [Table 3].
Table 3: Baseline to post-baseline change in laboratory parameters

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The mean ± SD QTc at baseline and EOT visits were 419.1 ± 24.48 and 424.0 ± 25.88 ms, respectively. Seven patients (11.7%) were reported to have abnormal ECG results at EOS; however, these were not clinically significant. One patient had raised QTc interval of ≥500 ms (529 ms) at the EOT visit. Two patients had an increase in QTc interval of ≥60 ms from baseline to EOT visit [Table 3].

 » Discussion Top

This postmarketing Phase IV study provides real-world evidence of the safety of once-daily 80 mg osimertinib in adult patients with EGFR T790M mutation-positive metastatic NSCLC, who had progressed on prior EGFR-TKIs therapy.

Three-fourths (75.0%) of the patient population reported at least one TEAE – mild or moderate – in most cases. Grade ≥3 TEAEs were found in 11.7% of patients. Treatment-related TEAEs were reported for approximately 18.0% of the patients; all being of mild or moderate severity. Three fatal events were observed in the study, which were not related to the study drug, including one event of disease progression. The rate of AEs was similar to that reported by Noronha et al.[32] in 13 patients in India with osimertinib use for comparatively lesser duration (median duration of 2.5 months) than our study (126 days, approximately 4 months). In the pivotal AURA 3 trial with 8.6 months of the mean duration of treatment, AE rates were higher (grade ≥3: 23%; treatment-related TEAEs: 83%, grade ≥3: 16%), which may be due to longer duration of safety assessment period compared to our current study.[16] However, ASTRIS real-world study across 17 countries in patients with similar characteristics reported lower rates of overall AEs (30%) and SAEs (21%) with osimertinib use.[31] In Asia, a Korean real-world study reported at least one AE in 95.7% patients and treatment-related TEAEs in 69.6% patients.[35]

In our study, the most commonly reported TEAEs were fatigue, decreased appetite, and mucosal inflammation; gastrointestinal disorders such as diarrhea, constipation, nausea, and vomiting; and skin conditions like rash and pruritus. Increased blood CPK, dyspnea (including exertional), and fatigue were the events with the highest incidences (10.0% each). The TEAEs reported for more than one patient were increased blood CPK, diarrhea, vomiting, fatigue, mucosal inflammation, and increased transaminases. Although the frequency was low, the nature of TEAEs was similar to those reported earlier in AURA 3 (diarrhea 41%, rash 34%, dry skin 23%),[16] pooled analysis of two Phase II AURA studies (rash 42%, diarrhea 39%, dry skin 32%),[26] and a real-world study from New Zealand (gastrointestinal 35%, skin 19%)[36] and an Indian real-world study (grade 1/2 rash 27.2%).[32] In first-line use of osimertinib, a similar safety profile was seen in FLAURA study (rash 58%, diarrhea 58%, dry skin 36%)[28] and Asian subset of FLAURA (rash 50%, diarrhea 54%), and was consistent with that observed for standard EGFR-TKI group.[37]

ASTRIS study, however, presented a different picture, with pneumonia (2%) and pulmonary embolism (2%) being among the most common TEAEs. AESIs such as ILD were reported in 28 (1%) patients. Twelve patients (<1%) had grade ≥3 ILD or a pneumonitis-like event, of whom four (<1%) patients had a fatal outcome.[31] In a Japanese real-word study in 3578 EGFR T790M-positive NSCLC patients on second-line osimertinib for 343 days, adverse drug reaction (ADR) of ILD was reported for 6.8% (245/3578) of patients, of whom 2.9% (104/3578) were grade ≥3; in case of 29 (11.8%) patients, it was fatal.[38] A little lesser percentage of patients in AURA 3 study had ILD-like AEs (10 [4%] patients). Dyspnea was reported in 24 (9%) patients, of whom three patients had grade ≥3 severity.[16] A recent meta-analysis of pivotal trials of osimertinib also reported a similar safety profile of osimertinib, in addition to pneumonia being common grade ≥3 AE.[39] Although dyspnea (including exertional) was reported in 10% of cases in our study, none of the study patients had a diagnosis of ILD/pneumonitis during the study conduct; dyspnea may have been because of the background disease condition. All the dyspnea events were mild or moderate, except for severe and fatal dyspnea in one patient each. Among the SAEs reported for about 12.0% of our patients, dyspnea was the only SAE reported for more than one patient, which was not related to osimertinib. However, as dyspnea was among the most common AEs observed in the study, a careful assessment of all patients with an acute onset and/or unexplained worsening of dyspnea, cough, and fever should be performed to exclude ILD while on treatment with osimertinib.

Cardiovascular AEs have been associated with cancer therapies. In pooled analysis AURA and AURA 2, an AE of QT prolongation was reported in 21/411 (5%) patients (grade 3, n = 5) without reports of cardiac arrhythmia. One patient with asymptomatic grade 3 QT prolongation had a recorded QT interval value >500 ms, >90 ms increase from baseline.[26] Similarly, in our study, only one patient had QT interval of ≥500 ms at one instance (last dosing day of Cycle 6) and an increase of ≥60 ms in QT interval from baseline to EOT visit. Our study reported increased blood CPK to be related to the study drug in 6.7% patients, and this was the reason for dose interruption in two patients. In a post hoc analysis of cardiac events data of AURA and FLAURA studies, 3.9% of patients had ≥ 10% decrease in left ventricular ejection fraction (LVEF) from baseline. Although data did not support a causal relationship between osimertinib and cardiac failure, cardiac monitoring at baseline and during osimertinib use is advised.[40] In the Japanese real-word study, the ADR of QT interval prolongation was seen in 1.3% (45/3578; grade ≥3, 0.1% [5/3578]) of patients.[38] In ASTRIS, 75/3015 (3%) patients had QT prolongation, with none resulting in life-threatening, disabling, or fatal outcomes.[31] The evidence generated so far suggests that although cardiotoxicity with osimertinib use is not yet established, QT interval prolongation has been reported.[41] Hence, osimertinib should be used after cardiac function assessment at baseline along with monitoring at regular intervals with ECG as well as LVEF as appropriate.[40]

Anemia, neutropenia, and thrombocytopenia were reported as treatment-emergent SAEs for only one patient (1.7%), which led to study drug discontinuation. Thrombocytopenia has been reported by Noronha et al.[32] (two patients, 18.1%). In Phase II TREM study using osimertinib in both T790M-positive and T790M-negative patients with EGFR-mutated advanced NSCLC who were previously treated with TKIs, there was a statistically significant decrease in platelet count from baseline to week 2 by 88.4 × 109/L (P < 0.001), whereas there was no significant change from week 2 until week 16. The drop from baseline until week 2 was significantly larger in patients with a baseline count above 300 × 109/L. Baseline platelet count was the only baseline factor correlated to a decrease in platelet count during the first 2 weeks of treatment with osimertinib (P < 0.001).[42] Thus, patients need to be closely monitored for platelet decrease while on osimertinib.

The study drug discontinuation rate due to TEAEs was much lower in our study (13.3%). In ASTRIS study, these rates were comparatively higher (dose modification, 14% and discontinuation, 6% patients).[31]

Our study was the second largest study in India after Noronha et al.'s study[32] that assessed the safety of osimertinib when administered in a second-line setting for six cycles. There could be some limitations of this current study possibly because of underreporting of AEs by patients or caregivers due to the disease condition itself. However, underreporting of SAEs and fatal AEs is unlikely even in real-world studies. Low incidence of SAEs, grade ≥3, and fatal AEs, as well as low rate of study drug discontinuations due to TEAEs in our study suggest that osimertinib is well tolerated and safe in our patient population. With emerging evidence, osimertinib is now recommended as the preferred first-line EGFR-TKI option and is approved for treatment of adult patients with EGFR-positive metastatic NSCLC with activating EGFR mutations[17],[19],[28] and as an adjuvant therapy after complete tumor resection in adult patients with early-stage (stage IB–IIIA) NSCLC, whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations based on ADAURA trial.[17],[43] The evidence available so far confirms favorable safety profile of osimertinib. Upcoming evidence and ongoing trials with evaluation of osimertinib in additional settings such as neoadjuvant before surgical resection in early stage NSCLC & consolidation in patients with Stage III unresectable EGFR-mutated NSCLC will further strengthen the knowledge of safety profile of osimertinib.

 » Conclusion Top

Overall, the safety profile of osimertinib 80 mg tablet was found to be favorable in Indian patients with metastatic EGFR T790M mutation-positive NSCLC who had progressed on or after EGFR-TKI therapy. No new safety concerns other than those known with the product use were observed in this study. No change in the benefit–risk profile of the drug was observed.


The authors would like to thank AstraZeneca Pharma India Ltd., and Covance Scientific Services & Solutions Pvt. Ltd the Contract Research Organization for supervising the study, providing administrative support for the development of this manuscript. Medical writing assistance was provided by Neelam Joglekar from Covance Scientific Services & Solutions Pvt. Ltd in accordance with GPP3 guidelines (

Financial support and sponsorship

AstraZeneca Pharma India Ltd.

Conflicts of interest

There are no conflicts of interest.

 » References Top

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  [Table 1], [Table 2], [Table 3]


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