|ORIGINAL ARTICLE: GERIATRIC ONCOLOGY SECTION
|Year : 2021 | Volume
| Issue : 2 | Page : 270-276
Immune checkpoint inhibitors in older patients with solid tumors: Real-world experience from India
George Abraham, Kunal N Jobanputra, Vanita Noronha, Vijay M Patil, Nandini S Menon, Shreya C Gattani, Kumar Prabhash
Department of Medical Oncology, Tata Memorial Centre, Mumbai, Maharashtra, India
|Date of Submission||27-Apr-2021|
|Date of Decision||21-May-2021|
|Date of Acceptance||10-Jun-2021|
|Date of Web Publication||30-Jun-2021|
Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Parel, Mumbai - 400 012, Maharashtra
Source of Support: None, Conflict of Interest: None
Background: Older patients with cancer are underrepresented in most immunotherapy trials. Therefore, there is an urgent and unmet need for real-world data on the efficacy and safety of immune checkpoint inhibitors (ICIs) in older patients with cancer.
Objectives: This study was aimed at analyzing the demographic pattern, treatment-related outcomes, and toxicities of ICIs in older patients with solid tumors.
Materials and Methods: This retrospective study was conducted in the Department of Medical Oncology of the Tata Memorial Hospital, a tertiary cancer care center in Mumbai, India. Patients aged ≥ 60 years with histologically confirmed malignancies of the thoracic, head and neck and genitourinary systems who were treated with ICIs between August 2014 and February 2021, and had received at least 2 cycles of ICI were enrolled in the study. Data related to the demographic profile and pattern of care were obtained from the electronic medical records and physical patient files. Patient management was decided in a multidisciplinary tumor board meeting. The primary endpoint of the study was overall survival (OS). The secondary endpoints were objective response rate (ORR), progression-free survival (PFS), and rate of immune-related adverse events.
Results: There were 150 patients included in the study. The most common indications for ICI use were non-small-cell lung cancer (52.7%) and head and neck squamous cell carcinoma (17.3%). Nivolumab was the most common ICI used in 119 (79.4%) patients. ICIs were used in the palliative setting in 144 (96%) patients. A total of 76 (50.6%) patients received ICIs as second-line therapy. The median number of cycles of ICI received was 5 (interquartile range, 3.0–9.5). The ORR to ICIs was 30%, and the clinical benefit rate was 52%. ICIs were discontinued due to toxicities in 4 (2.7%) patients. The median PFS and OS were 4.23 (95% confidence interval [CI], 1.38–7.08) months and 8.6 (95% CI, 4.9–12.2) months, respectively. Baseline performance status was the most significant prognostic factor for PFS and OS in the multivariate analysis. In addition, age, male sex, and comorbid conditions such as chronic kidney disease negatively impacted the OS.
Conclusion: Our study shows that ICIs are efficacious and well tolerated in older Indian patients with solid tumors. There is an emerging need for larger prospective studies on ICIs with the incorporation of geriatric assessment scores in this vulnerable patient population.
Keywords: Geriatric, immune check point inhibitors, immune related adverse events, real world data, real world evidence, RWE
|How to cite this article:|
Abraham G, Jobanputra KN, Noronha V, Patil VM, Menon NS, Gattani SC, Prabhash K. Immune checkpoint inhibitors in older patients with solid tumors: Real-world experience from India. Cancer Res Stat Treat 2021;4:270-6
|How to cite this URL:|
Abraham G, Jobanputra KN, Noronha V, Patil VM, Menon NS, Gattani SC, Prabhash K. Immune checkpoint inhibitors in older patients with solid tumors: Real-world experience from India. Cancer Res Stat Treat [serial online] 2021 [cited 2021 Sep 21];4:270-6. Available from: https://www.crstonline.com/text.asp?2021/4/2/270/320149
| Introduction|| |
Immune checkpoint inhibitors (ICIs) have contributed significantly to the therapeutic armamentarium for difficult-to-treat cancers over the past decade. The difference in the toxicity patterns of ICIs and chemotherapy along with the decreased incidences of myelosuppression, neuropathy, and gastrointestinal toxicities with ICIs makes them a tolerable and attractive option in the vulnerable patient population, especially in older adults and those with multiple comorbidities and poor performance status (PS).
Cancer-related mortality is higher in the older population. Indian men and women aged ≥60 years have a 15 and 8 times higher incidence of cancer, respectively, than their counterparts aged <60 years. According to the GLOBOCAN 2018 and 2020 databases, the projected number of cancer cases among those aged ≥70 years will rise from 0.24 million in 2018 to 0.54 million by 2040, and the projected number of cancer deaths in this age group will increase from 0.19 million in 2018 to 0.43 million by 2040 in India.,,, The incidence of cancer globally is predicted to increase by 47% from 19.3 million cases in 2020 to 28.7 million in 2040. Hence, there is an emerging need to improve the strategies for cancer treatment and supportive care in older patients.
Older patients with cancer are underrepresented in phase III clinical trials in view of their chronological age, comorbidities, and poor PS., Thus, the results of the landmark ICI trials cannot be readily extrapolated to older patients with cancer. In addition, there are specific issues in this patient population, such as the high prevalence of polypharmacy which could have a detrimental effect on the efficacy, tolerability, and safety of novel agents such as ICIs., Baseline functional status and mobility, incidence of falls, depression, and decline in cognition and nutrition could have an additional impact, which makes the older patient population distinct with regard to cancer-related outcomes., An Eastern Cooperative Oncology Group (ECOG) PS of 2 is considered a negative predictive factor for cancer-related survival in various therapeutic trials. Therefore, patients with a poor PS have been excluded from large phase III ICI trials. However, these patients are routinely seen in the clinic, and treatment decisions need to be made without a robust evidence base. The results of the KEYNOTE studies show a comparable safety and efficacy of pembrolizumab monotherapy in older patients with non-small-cell lung cancer (NSCLC) with programmed death-ligand 1 (PD-L1) expression >1% in the trial settings. However, real-world data for the same are scarce. Thus, there is an urgent and unmet need for real-world data on the efficacy of ICIs in older patients with cancer.
There are observational studies which suggest that older and vulnerable patients are more likely to develop immune-related adverse events (iRAEs), resulting in treatment discontinuation. Furthermore, the incidence of iRAEs, effect of ICI on the quality of life, and the effect of immune-senescence on ICI-related toxicities and outcomes are some of the underexplored research areas in older patients with cancer. Hence, in this study, we aimed to analyze the demographic pattern, comorbidities, treatment-related outcomes, and toxicity of ICIs in older Indian patients with solid tumors.
| Materials and Methods|| |
General study details
This retrospective study on patients receiving ICIs was conducted in the Department of Medical Oncology at the Tata Memorial Hospital, a tertiary cancer care center in Mumbai, India, between August 2014 and February 2021. The study was approved by the institutional ethics committee (IEC) for the retrospective evaluation of the use of ICIs in patients with solid tumors (reference project number-900742) and the IEC granted permission for a waiver of the requirement of written informed consent for enrollment in the study given the retrospective nature of the study. The protocol is added as Supplementary Appendix-1-Study Protocol. All patients provided written informed consent for therapy. The study was conducted in accordance with the various ethical principles established by the Declaration of Helsinki and the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use's Guideline for Good Clinical Practice and the Indian Council of Medical Research guidelines. The study was not registered in a public Clinical Trials Registry due to the retrospective nature of the study. There was no funding utilized for the study.
Patients aged ≥60 years and diagnosed with histologically confirmed thoracic, urological, or head and neck malignancies who were treated with ICIs for various indications from August 2014 to February 2021 at our institute and had received at least 2 cycles of ICI were enrolled in the study. Patients for whom no clinical details could be obtained, who took treatment at other centers, and those who were lost to follow-up after being planned for immunotherapy were excluded from the study.
The primary endpoint of the study was overall survival (OS). The secondary endpoints were objective response rate (ORR), progression-free survival (PFS), and iRAEs.
The data were collected from the electronic medical records and physical files of the patients. Patient management was decided in a multidisciplinary tumor board meeting based on the prior lines of treatment received, medical history, comorbidities, economic background, and medical insurance coverage. The data related to the demographic profile of the patients, pattern of care, PFS, and OS were extracted. The practice patterns of ICI administration were captured, and the number of cycles of ICI administered was recorded. Toxicity assessment was performed based on the clinical examination and blood investigations, such as complete blood count, liver function test, renal function test, and thyroid profile. The adverse events were reported as per the Common Terminology Criteria for Adverse Events, version 5.0 (U. S. Department of Health and Human Services, Washington D. C, USA). The response was assessed using the clinical history, examination, and computed tomography scans performed approximately once every 2 months and evaluated as per the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Patients who could not afford full-dose immunotherapy were given the option of low-dose immunotherapy, and nivolumab was administered at a dose of 1 mg/kg once every 3 weeks in such patients. The data were censored on March 22, 2021.
ORR was defined as the proportion of patients who had radiologic complete or partial response (CR or PR), whichever was the best response after the start of treatment with ICIs. Clinical benefit rate was defined as the proportion of patients who had stable disease (SD), PR, or CR, whichever was the best response after the start of treatment with ICI. Radiological assessment was correlated with clinical assessment of the cancer-related symptoms and signs of the patient at approximately three monthly intervals. Interim additional imaging was done if there was clinical suspicion of disease progression. Pseudoprogression was defined as occurrence of SD, PR, or CR as per RECIST version 1.1 on continuation with ICI after the occurrence of progressive disease (PD). PFS was defined as the period from the start of treatment with ICI to disease progression or death due to any cause or the last follow-up in the absence of disease progression. OS was defined as the period from the start of treatment with ICI to death due to any cause or last follow-up in the surviving patients.
A formal sample size calculation was not done for the study because of its retrospective nature. All patients fulfilling the eligibility criteria were enrolled in the study. The data were entered into Microsoft Excel and analyzed using the Statistical Package for the Social Sciences (SPSS) (IBM corp. Released 2012, IBM SPSS statistics for Windows, software version 25.0, Armonk, NY, USA: IBM corp.). Descriptive statistics such as mean (standard deviation) and median (range or interquartile range or 95% confidence intervals [95% CI]) were used for qualitative variables. The Chi-squared test was used for the comparison of quantitative variables for larger samples, whereas the Fisher's exact test was used for smaller samples. Survival analysis for OS and PFS was performed using the Kaplan–Meier method, and differences were compared using the log-rank test. The follow-up period in the surviving patients was calculated using the reverse Kaplan–Meier method. Hazard ratio (HR) was calculated using the Cox regression analysis., P < 0.05 was considered to denote statistical significance.
| Results|| |
Of the 455 patients who received ICIs for various approved indications in our unit, 150 patients fulfilled the eligibility criteria and were selected for analysis [Figure 1]. The baseline characteristics of the patients are shown in [Table 1]. The most common indications for ICI use were NSCLC and head and neck squamous cell carcinoma (HNSCC). Of the 79 patients with NSCLC who underwent biomarker testing, 23 (29.1%) were positive for driver mutations. Of the remaining 56 patients with NSCLC with no driver mutations, PD-L1 testing was performed for 24 (42.8%) patients. The PD-L1 expression was <1% in 6 (25%) patients, 1%–50% in 4 (16.6%) patients, and >50% in 14 (58.3%) patients.
|Figure 1: Patient recruitment flow chart for the study on the real-world data on immune checkpoint inhibitors in older Indian patients with cancer. ACRONYMS: ICI-immune checkpoint inhibitors; GI-gastrointestinal|
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|Table 1: Baseline characteristics of older Indian patients with cancer who received immune checkpoint inhibitors|
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Of the 150 patients, 144 (96%) had stage IV (unresectable or metastatic) disease, and ICIs were used in these patients in the palliative setting; the remaining 6 (4%) patients had stage III NSCLC and received consolidation durvalumab post-chemoradiation. ICIs were used in the first line in 44 (29.4%) patients, second line in 76 (50.6%), and subsequent lines in 30 (20%). Nivolumab was the most common ICI used in 119 (79.4%) patients. The median number of cycles of ICI administered was 5 (interquartile range, 3.0–9.5). Of the 79 patients with NSCLC, 36 (45.5%) patients received the ICI as monotherapy, i.e. without combination chemotherapy in the second line after progression on first-line tyrosine kinase inhibitors (n = 23) or chemotherapy with pemetrexed and carboplatin (n = 13).
First-line ICIs in combination with chemotherapy (pemetrexed/paclitaxel and carboplatin) were administered in 26 (32.9%) patients. ICI without chemotherapy in the third or subsequent lines was administered in 17 (21.5%) patients with NSCLC. A total of 24 (92.3%) patients with HNSCC received nivolumab alone without chemotherapy in the second line or beyond post progression on platinum-based therapy with or without cetuximab (n = 22) (platinum resistant/refractory progression) or triple metronomic chemotherapy (n = 2). In 14 (93.3%) patients with metastatic renal cell carcinoma, ICI alone was administered post progression on tyrosine kinase inhibitors in the second line and beyond.
The radiological and clinical responses to ICIs as per RECIST version 1.1 are shown in [Table 2]. The ORR was 30% and the clinical benefit rate was 52%. The most common reason for cessation of therapy was disease progression in 93 (62%) patients. The driver mutation status of the patients with NSCLC and their response rates are shown in [Supplementary Table 1].
|Table 2: Immune checkpoint inhibitors used along with their dosage and best response rates|
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A total of 70 patients were alive at the median follow-up of 14.3 months (range, 0.1–36). There were 93 events for PFS. The median PFS with ICIs in our cohort was 4.23 (95% CI, 1.38–7.08) months [Figure 2]. The most common reason for cessation of therapy was disease progression. There were a total of 80 deaths. The median OS with ICIs was 8.6 (95% CI, 4.9–12.2) months [Figure 3]. The median durations of response in responders (CR + PR) and non-responders (SD + PD) were 11.8 (95% CI, 6.05–17.55) months and 2.5 (95% CI 1.89–3.17) months, respectively, with P < 0.0001 and HR of 0.29 (95% CI, 0.17–0.49) as shown in [Supplementary Figure 1]. The median OS in responders and non-responders was 26.5 (95% CI, 8.74–44.39) months and 4.6 (95% CI, 3.29–5.98) months, respectively, with P < 0.0001 and HR of 0.30 (95% CI, 0.16–0.51) as shown in [Supplementary Figure 2]. A survival analysis for the patients who received low-dose immunotherapy was not performed in view of the small number of patients in the cohort. In the subset analysis for NSCLC, the median PFS was 3.9 (95% CI, 1.50–7.96) months and the median OS was 9.2 (95% CI, 4.60–13.87) months. Subset analysis for the other histologies was not performed in view of the small number of patients for the individual cancer types in our cohort. The ECOG PS at the start of treatment with ICIs was found to be the most significant prognostic factor for PFS and OS in the multivariate analysis. In addition, age, male sex, and comorbidities such as chronic kidney disease had a negative impact on the OS [Supplementary Table 2].
|Figure 2: Kaplan–Meier curve depicting the progression-free survival of the older patients with cancer who received immune checkpoint inhibitors. There were 93 events for progression. At a median follow up of 14.3 months (95% confidence interval, 12.6–15.9), the median progression-free survival with immune checkpoint inhibitor in the older patients was 4.23 months (95% confidence interval, 1.38–7.08)|
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|Figure 3: Kaplan–Meier curve depicting the overall survival of the older patients with cancer who received immune checkpoint inhibitors. There were 80 deaths. At a median follow up of 14.3 months (95% confidence interval 12.6–15.9), the median OS with immune checkpoint inhibitors was 8.6 months (95% confidence interval, 4.9–12.2)|
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Information related to toxicities was available for 112 patients. The number of patients who developed one or more irAEs of any grade was 57 (50.8%); severe irAEs were documented in 10 (8.9%) patients. The incidence of grade 1 or 2 thyroiditis was 5 (4.5%) and colitis was 6 (5.4%). Thyroiditis was suspected when there was an increase in the level of thyroid-stimulating hormone, which temporally correlated with the start of ICI in euthyroid patients and hypothyroid patients with regular intake of optimal doses of levothyroxine. There were no severe cases of colitis, and hence, colonoscopic biopsy was not performed in any patient. Details of the various adverse events related to ICI are shown in [Supplementary Table 3]. Discontinuation of ICIs due to toxicities was reported in 4 (2.7%) patients (3 due to pneumonitis and 1 due to transaminitis).
| Discussion|| |
In our study, the response rate to ICIs in older Indian patients with solid tumors was found to be 30%, with a median PFS and OS of 4.23 and 8.6 months, respectively. The PS of the patient at baseline was found to be the most significant factor predictive of both PFS and OS on the multivariate analysis. In addition, age, male sex, and the presence of chronic kidney disease at baseline were significant factors in the multivariate analysis for OS. No plateauing of the survival curve was observed beyond 3 years, suggesting that we were unable to identify a subset of patients who attained a very long-term survival benefit of more than 3 years. Similarly, plateauing of the survival curve beyond 3 years was not observed in the Flatiron study, suggesting that real-world datasets may differ from trial datasets, which have consistently reported long-term survival benefits with ICIs. The exact reason for this is unclear; the retrospective nature of the studies performed in the real-world settings with a higher proportion of censored data resulting from loss to follow-up when compared to the prospective trial settings may be a contributory factor.
The clinical benefit rate and ORR with ICIs in our older Indian patients with cancer were comparable to those described in the Western literature. The PFS and OS in older patients with cancer in the real-world setting have been relatively similar to those described in the clinical trials in various cancer types, especially in head and neck cancers, lung cancers,, urothelial and renal cell carcinomas. Although most of the clinical trials have reported similar efficacy and safety in the subgroup analyses for those aged <65 years and ≥65 years, the majority of the patients were aged around 65 years, thus blunting the differences that could have arisen otherwise specifically in the older patients., Muchnik et al. have reported the largest real-world data on the use of ICIs in the geriatric patients with NSCLC, which mirror our data in terms of the ECOG PS at baseline being the most important determinant of outcomes, even more than the chronological age of the patient. The well-known pattern of benefit of immunotherapy with a select population of responders having a prolonged PFS and OS when compared to non-responders holds true in the geriatric population as well as per the current study.
Our real-world experience revealed a lower rate of iRAEs than that reported in the published data for older patients with cancer. This could be due to the retrospective nature of the study and the lower age cutoff that was used to select the patients; while our age cutoff for geriatric population was ≥60 years, Muchnik et al. selected patients aged ≥70 years. ICIs appeared to be well tolerated and safe in our cohort with Grade 3/4 toxicities and treatment discontinuations comparable to published literature.,, There was no mortality due to iRAEs in our cohort. The age cutoff of ≥60 years for patient selection and the absence of patients with cutaneous melanomas were the major differences between our study and other similar studies on efficacy and safety of ICIs in the geriatric population.,, The multivariate analysis in our study showed baseline chronic kidney disease and chronological age to be significant predictive factors for OS, which is different from the existing real-world data. Although results in the geriatric population at our center are similar to the existing real-world data from India with respect to the efficacy and toxicity profile of ICIs, our study focused exclusively on the geriatric population and had a longer follow-up duration for PFS and OS.
To the best of our knowledge, our study, by far, provides the largest real-world data on the use of ICIs in older patients with cancer and has adequate representation of patients with comorbidities and poor PS and yet has demonstrated comparable efficacy and a favorable safety profile. Most patients received ICIs in the second line, similar to the other studies that included patients of all age groups., Our study was limited by its retrospective design, lack of data on the quality of life of geriatric patients and baseline geriatric assessment, and the heterogenous population enrolled. There is an emerging need for prospective studies on the use of ICIs in older patients with cancer and the benefit of baseline geriatric assessment in this vulnerable group in predicting the responses and iRAEs.
The real-world scenarios of ICI use are largely determined by the financial status of the patients and the availability of reimbursements, resulting in the poor accessibility of ICIs in Indian patients., To improve the access to ICIs, the use of low-dose immunotherapy may be considered, and this strategy was followed in 13 (8.7%) patients in our study.,, Thus, our study offers a hope for extending the treatment horizon with ICIs in our older patients with cancer with multiple comorbidities and poor PS who are unfit for chemotherapy.
| Conclusion|| |
Our study shows that ICIs are efficacious and well tolerated in older Indian patients with solid tumors in the real-world setting. However, there is an emerging need for larger prospective studies on ICI with the incorporation of geriatric assessment scores in this vulnerable patient population.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| Supplementary Appendix 1|| |
| References|| |
|1.|Rhyner Agocs G, Dougoud-Chauvin V, Betticher D. Immunotherapy: Also in elderly patients? Rev Med Suisse 2019;15:1512-5.
|2.|van Holstein Y, Kapiteijn E, Bastiaannet E, van den Bos F, Portielje J, de Glas NA. Efficacy and adverse events of
immunotherapy with checkpoint inhibitors in older patients with cancer. Drugs Aging 2019;36:927-38.
|3.|Pedersen JK, Engholm G, Skytthe A, Christensen K; Academy of Geriatric Cancer Research (AgeCare). Cancer and aging: Epidemiology and methodological challenges. Acta Oncol 2016;55 Suppl 1:7-12.
|4.|Yeole BB, Kurkure AP, Koyande SS. Geriatric cancers in India: An epidemiological and demographic overview. Asian Pac J Cancer Prev 2008;9:271-4.
|5.|The Lancet. GLOBOCAN 2018: Counting the toll of cancer. Lancet 2018;392:985.
|6.|Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018;68:394-424.
|7.|Mathur P, Sathishkumar K, Chaturvedi M, Das P, Sudarshan KL, Santhappan S, et al
. Cancer statistics, 2020: Report from national cancer registry programme, India. JCO Glob Oncol 2020;6:1063-75.
|8.|Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al
. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021;71:209-49.
|9.|Pallis AG, Hatse S, Brouwers B, Pawelec G, Falandry C, Wedding U, et al
. Evaluating the physiological reserves of older patients with cancer: The value of potential biomarkers of aging? J Geriatr Oncol 2014;5:204-18.
|10.|Kanesvaran R, Cordoba R, Maggiore R. Immunotherapy in older adults with advanced cancers: Implications for clinical decision-making and future research. Am Soc Clin Oncol Educ Book 2018;38:400-14.
|11.|Sharma M, Loh KP, Nightingale G, Mohile SG, Holmes HM. Polypharmacy and potentially inappropriate medication use in geriatric oncology. J Geriatr Oncol 2016;7:346-53.
Noronha V, Ramaswamy A, Gattani SC, Castelino R, Krishnamurthy MN, Menon N, et al.
Polypharmacy and potentially inappropriate medication use in older Indian patients with cancer: A prospective observational study. Cancer Res Stat Treat 2021;4:67-73. [Full text]
|13.|Mohile SG, Dale W, Somerfield MR, Schonberg MA, Boyd CM, Burhenn PS, et al
. Practical assessment and management of vulnerabilities in older patients receiving chemotherapy: ASCO guideline for geriatric oncology. J Clin Oncol 2018;36:2326-47.
Noronha V, Ramaswamy A, Dhekle R, Talreja V, Gota V, Gawit K, et al.
Initial experience of a geriatric oncology clinic in a tertiary cancer center in India. Cancer Res Stat Treat 2020;3:208-17. [Full text]
|15.|Friedlaender A, Banna GL, Buffoni L, Addeo A. Poor-performance status assessment of patients with non-small cell lung cancer remains vague and blurred in the immunotherapy era. Curr Oncol Rep 2019;21:107.
|16.|Nosaki K, Saka H, Hosomi Y, Baas P, de Castro G Jr, Reck M, et al
. Safety and efficacy of pembrolizumab monotherapy in elderly patients with PD-L1-positive advanced non-small-cell lung cancer: Pooled analysis from the KEYNOTE-010, KEYNOTE-024, and KEYNOTE-042 studies. Lung Cancer 2019;135:188-95.
|17.|Hong H, Wang Q, Li J, Liu H, Meng X, Zhang H. Aging, cancer and immunity. J Cancer 2019;10:3021-7.
|18.|Park HJ, Kim KW, Pyo J, Suh CH, Yoon S, Hatabu H, et al
. Incidence of pseudoprogression during immune checkpoint inhibitor therapy for solid tumors: A systematic review and meta-analysis. Radiology 2020;297:87-96.
Chakraborty S. A step-wise guide to performing survival analysis. Cancer Res Stat Treat 2018;1:41-5. [Full text]
Dessai S, Simha V, Patil V. Stepwise cox regression analysis in SPSS. Cancer Res Stat Treat 2018;1:167-70. [Full text]
Dessai S, Patil V. Testing and interpreting assumptions of COX regression analysis. Cancer Res Stat Treat 2019;2:108-11. [Full text]
|22.|Schwartzberg L, Korytowsky B, Penrod JR, Zhang Y, Le TK, Batenchuk C, et al
. Real-world clinical impact of immune checkpoint inhibitors in patients with advanced/metastatic non-small cell lung cancer after platinum chemotherapy. Clin Lung Cancer 2019;20:287-96.e4.
|23.|Noronha V, Abraham G, Patil V, Joshi A, Menon N, Mahajan A, et al. A real-world data of Immune checkpoint inhibitors in solid tumors from India. Cancer Med 2021;10:1525-34.
Monteverdi S, Vita E, Sartori G, Ferrara MG, D'Argento E, Tortora G, et al.
Long-term survivors with immunotherapy in advanced NSCLC: Is 'cure' within reach? Transl Cancer Res 2020;9:409-14.
|25.|Quinn C, Garrison LP, Pownell AK, Atkins MB, de Pouvourville G, Harrington K, et al
. Current challenges for assessing the long-term clinical benefit of cancer immunotherapy: A multi-stakeholder perspective. J Immunother Cancer 2020;8:
|26.|Fox B, de Toro Carmena M, Álvarez Álvarez R, Calles Blanco A, López López C, Pérez Ramírez S, et al
. Efficacy and safety of immune checkpoint inhibitor immunotherapy in elderly cancer patients. Clin Transl Oncol 2020;22:555-62.
|27.|Ferris RL, Blumenschein G Jr., Fayette J, Guigay J, Colevas AD, Licitra L, et al
. Nivolumab vs investigator's choice in recurrent or metastatic squamous cell carcinoma of the head and neck: 2-year long-term survival update of CheckMate 141 with analyses by tumor PD-L1 expression. Oral Oncol 2018;81:45-51.
Theelen WS, Baas P. Pembrolizumab monotherapy for PD-L1≥50% non-small cell lung cancer, undisputed first choice? Ann Transl Med 2019;7:S140.
|29.|Herbst RS, Baas P, Kim DW, Felip E, Pérez-Gracia JL, Han JY, et al
. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): A randomised controlled trial. Lancet 2016;387:1540-50.
|30.|Bellmunt J, de Wit R, Vaughn DJ, Fradet Y, Lee JL, Fong L, et al
. Pembrolizumab as second-line therapy for advanced urothelial carcinoma. N Engl J Med 2017;376:1015-26.
|31.|Motzer RJ, Escudier B, McDermott DF, George S, Hammers HJ, Srinivas S, et al
. Nivolumab versus everolimus in advanced renal-cell carcinoma. N Engl J Med 2015;373:1803-13.
|32.|Poropatich K, Fontanarosa J, Samant S, Sosman JA, Zhang B. Cancer immunotherapies: Are they as effective in the elderly? Drugs Aging 2017;34:567-81.
|33.|Muchnik E, Loh KP, Strawderman M, Magnuson A, Mohile SG, Estrah V, et al
. Immune checkpoint inhibitors in real-world treatment of older adults with non-small cell lung cancer. J Am Geriatr Soc 2019;67:905-12.
|34.|Leroy V, Gerard E, Dutriaux C, Prey S, Gey A, Mertens C, et al
. Adverse events need for hospitalization and systemic immunosuppression in very elderly patients (over 80 years) treated with ipilimumab for metastatic melanoma. Cancer Immunol Immunother 2019;68:545-51.
|35.|Samani A, Zhang S, Spiers L, Mohamed AA, Merrick S, Tippu Z, et al
. Impact of age on the toxicity of immune checkpoint inhibition. J Immunother Cancer 2020;8:
|36.|Daste A, Domblides C, Gross-Goupil M, Chakiba C, Quivy A, Cochin V, et al
. Immune checkpoint inhibitors and elderly people: A review. Eur J Cancer 2017;82:155-66.
Cavalin Silva C, Herchenhorn D. Treating the elderly with immune checkpoint inhibitors: Real life experience from a large Brazilian center. J Clin Orthod 2018;36:e15077.
|38.|Gupta VG, Rangaraju RR, Abbas W, Bajpai P, Khetrapal R. Immune checkpoint inhibitors: Real-world experience from India in advanced solid cancers that have progressed on chemotherapy. South Asian J Cancer 2019;8:65-8.
Abbas W, Aggarwal A, Pankaj P, Jain R. Real-world data of second-line immunotherapy in metastatic clear cell renal cell carcinoma: A retrospective study. Cancer Res Stat Treat 2021;4:55-60. [Full text]
Abraham G, Menon N, Patil VM, Joshi AP, Prabhash K. The efficacy of low-dose immunotherapy in head-and-neck cancer. Cancer Res Stat Treat 2019;2:268-9. [Full text]
Patil VM, Noronha V, Joshi A, Abhyankar A, Menon N, Banavali S, et al.
Low doses in immunotherapy: Are they effective? Cancer Res Stat Treat 2019;2:54-60. [Full text]
Talreja VT, Noronha V, Patil VM, Joshi A, Prabhash K. Desperate times, desperate measures: Low-dose nivolumab-induced remission in relapsed NSCLC. Cancer Res Stat Treat 2019;2:266-7. [Full text]
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2]