Correlation between different carboplatin dosing patterns and its toxicity analysis in patients with advanced lung cancers: A retrospective study.

OBJECTIVE: To evaluate the current NCI-CTEP recommendation and the clinical use of Calvert Formula-derived carboplatin dosing pattern in the treatment of advanced lung cancer patients and assess carboplatin-related toxicity in relation to the degree of dose fluctuation. METHODOLOGY: This retrospective study involved all histologically confirmed inoperable lung cancer patients receiving palliative-intent carboplatin or carboplatin-combination chemotherapy from 2012 to 2016 at Kingston Health Sciences Centre. The carboplatin dosing pattern and carboplatin-related toxicity were collected and analysed on SPSS IBM for Windows version 24.0 (IBM Corp., Armonk, NY, USA). Results were expressed in percentages and P values. RESULTS: Our findings ( N = 75) suggested that 24% of patients had a high-degree of fluctuation in carboplatin dose (>10% variation from initial dose) if carboplatin dose was readjusted with each new creatinine. In practice, 16% of patients had a fluctuation of greater than 10% in ordered dose in the absence of planned dose reductions. Our study found no significant association between prescribed high-risk dosing fluctuation (>10% increased from initial dose) and carboplatin-related toxicities. DISCUSSION AND CONCLUSION: In contrast to some prescribing recommendations such as NCI-CTEP, our study suggested that most medical oncologists incorporate new serum creatinine in calculating carboplatin dose for each cycle. Only 9% of patients were treated with a fixed dosing pattern (i.e. no fluctuation). Nonetheless, no significant associations were found between high-risk carboplatin dosing fluctuation and its-related toxicity. Whether such practice was due to the forcing function of the computer order entry system (CPOE), or conscious decisions by medical oncologists was unknown. Further analysis in evaluating physicians' preferences and influencing factors on dosing pattern decision would be recommended.

Motivation and preferences of exercise programmes in patients with inoperable metastatic lung cancer: a need assessment.

OBJECTIVES: The aim of this study is to investigate the motivation, ability, preferences, and perceived potential facilitating factors/barriers of patients with inoperable metastatic lung cancer towards exercise programmes. METHODS: This is a cross-sectional study using survey adopting the Theory of Planned Behaviour (TPB) to obtain patients' experience recruited through Odette Cancer Centre, Sunnybrook Health Sciences Complex. Results were expressed in percentages, P value, and Spearman's rho. RESULTS: Sixty patients were recruited from January 2014 to April 2014. Patients generally had a high level across TPB measures, with 63% of them indicating that they have the motivation to exercise. Significant association in relation to motivation was established on attitudes (importance, P = 0.005, rho = 0.326; helpfulness, P = 0.015, rho = 0.348; and easiness, P = 0.001, rho = 0.375) and subjective norm of close members (P = 0.0069, rho = 0.348) and healthcare professionals (P = 0.012, rho = 0.328). Being a non-smoker (P = 0.042, rho = 0.311), having a past exercise history prior to diagnosis (P = 0.000, rho = 0.563), and absence of COPD (P = 0.016, rho = -0.312) were also shown to have a significant association with motivation to exercise. DISCUSSIONS AND CONCLUSIONS: Patients were motivated to participate in an exercise programme despite contrary belief; however, they might have limited ability and preferred light intensity type of exercise such as walking. Their motivation to exercise was driven by different factors when compared to other cancer patient populations. Thus, it is important for healthcare professionals to understand the factors influencing their motivation and increase their awareness (only 26% of patients indicated receiving advice regarding exercise) to better the care towards patients with metastatic lung cancer.

Can Oncogenic Driver Alterations be Responsible for the Lack of Immunotherapy Efficacy in First-line Advanced Urothelial Carcinoma?

Urothelial carcinoma (UC) harbors many oncogenic alterations and the limited efficacy of first-line immunotherapy in this setting suggests that oncogenic alterations could have potential as a predictive biomarker for treatment decision-making. Antibody-drug conjugates (ADCs) may offer new avenues for biomarker-driven treatment in advanced UC, especially for patients with oncogenic alterations.

Survivals following discontinuation of PD-1 inhibitor treatment in advanced melanoma patients.

The aim of this study was to evaluate overall survival post-treatment discontinuation survival (OS PTD ) in advanced melanoma patients started on immunotherapy. This retrospective study included all unresectable advanced or metastatic melanoma patients who had permanent treatment discontinuation after receiving at least one cycle of palliative-intent programmed death-1 ± cytotoxic T-lymphocyte associated protein-4 inhibitor treatment from 2014 to 2019. Indications of permanent treatment discontinuation included treatment completion, toxicity or progression. OS PTD was defined as a time of permanent treatment discontinuation to the time of death. Our study ( N = 96) had 27, 12 and 57 patients who discontinued PD-1 inhibitor treatment due to treatment completion, toxicity and progression, respectively. Median treatment durations received for the treatment completion, toxicity and progression groups were 24, 6 and 3 months, respectively. As expected those patients who had disease progression on immunotherapy had very poor survival compared to those that completed treatment or stopped due to toxicity. A multivariable Cox model excluding the patients who progressed indicated no significant OS PTD differences between the toxicity and treatment completion group (HR, 0.894; 95% CI, 0.232-3.449; P = 0.871) who received single or dual immunotherapy. Our real-world study highlighted similar, durable survival at PD-1 inhibitor discontinuation due to either toxicity or treatment completion, despite longer treatment duration received in the completion group than toxicity group. Patients with progression on PD-1 inhibitor treatment have very poor survival. Our findings must be interpreted with caution due to its retrospective nature and small sample size.

Association of circadian timing of initial infusions of immune checkpoint inhibitors with survival in advanced melanoma.

Aims: Chronomodulation of immune checkpoint inhibitors (ICIs) is not well understood. The authors evaluated the circadian timing of initial ICI infusions. Patients & methods: A retrospective cohort study of patients with advanced melanoma (n = 121) was conducted. Results: Exclusive afternoon timing of the first four infusions was associated with worse overall survival (5.5 vs 24.9 months; p < 0.001) and progression-free survival (3.3 vs 7.6 months; p = 0.009) on Kaplan-Meier curves. In multivariable Cox analysis, the rate of overall survival was lower in patients who received all first four ICI infusions in the afternoon versus patients who received ≥1 of the first four infusions in the morning (hazard ratio: 2.4; p = 0.004). Conclusion: Deliberate morning scheduling for the first several ICI treatments may improve patient-centered outcomes.

Survival outcomes and predicting intracranial metastasis in stage III non-small cell lung cancer treated with definitive chemoradiation: Real-world data from a tertiary cancer center.

PURPOSE/OBJECTIVE: Around 30% of patients with non-small cell lung cancers (NSCLC) are diagnosed with stage III disease at presentation, of which about 50% are treated with definitive chemoradiation (CRT). Around 65-80% of patients will eventually develop intracranial metastases (IM), though associated risk factors are not clearly described. We report survival outcomes and risk factors for development of IM in a cohort of patients with stage III NSCLC treated with CRT at a tertiary cancer center. MATERIALS/METHODS: We identified 195 patients with stage III NSCLC treated with CRT from January 2010 to May 2021. Multivariable logistic regression was used to generate odds ratios for covariates associated with development of IM. Kaplan-Meier analysis with the Log Rank test was used for unadjusted time-to-event analyses. P-value for statistical significance was set at < 0.05 with a two-sided test. RESULTS: Out of 195 patients, 108 (55.4%) had stage IIIA disease and 103 (52.8%) had adenocarcinoma histology. The median age and follow-up (in months) was 67 (IQR 60-74) and 21 (IQR 12-43), respectively. The dose of radiation was 60 Gy in 30 fractions for148 patients (75.9%). Of the 77 patients who received treatment since immunotherapy was available and standard at our cancer center, 45 (58.4%) received at least one cycle. During follow-up, 84 patients (43.1%) developed any metastasis, and 33 (16.9%) developed IM (either alone or with extracranial metastasis). 150 patients (76.9%) experienced a treatment delay (interval between diagnosis and treatment > 4 weeks). Factors associated with developing any metastasis included higher overall stage at diagnosis (p = 0.013) and higher prescribed dose (p = 0.022). Factors associated with developing IM included higher ratio of involved over sampled lymph nodes (p = 0.001) and receipt of pre-CRT systemic or radiotherapy for any reason (p = 0.034). On multivariate logistical regression, treatment delay (OR 3.9, p = 0.036) and overall stage at diagnosis (IIIA vs. IIIB/IIIC) (OR 2.8, p = 0.02) predicted development of IM. These findings were sustained on sensitivity analysis using different delay intervals. Median OS was not reached for the overall cohort, and was 43.1 months for patients with IM and 40.3 months in those with extracranial-only metastasis (p = 0.968). In patients with any metastasis, median OS was longer (p = 0.003) for those who experienced a treatment delay (48.4 months) compared to those that did not (12.2 months), likely due to expedited diagnosis and treatment in patients with a higher symptom burden secondary to more advanced disease. CONCLUSIONS: In patients with stage III NSCLC treated with definitive CRT, the risk of IM appears to increase with overall stage at diagnosis and, importantly, may be associated with experiencing a treatment delay (> 4 weeks). Metastatic disease of any kind remains the primary life-limiting prognostic factor in these patients with advanced lung cancer. In patients with metastatic disease, treatment delay was associated with better survival. Patients who experience a treatment delay and those initially diagnosed at a more advanced overall stage may warrant more frequent surveillance for early diagnosis and treatment of IM. Healthcare system stakeholders should strive to mitigate treatment delay in patients with locally NSCLC to reduce the risk of IM. Further research is needed to better understand factors associated with survival, treatment delay, and the development of IM after CRT in the immunotherapy era.

Improved overall survival in dual compared to single immune checkpoint inhibitors in BRAF V600-negative advanced melanoma.

Aim: To evaluate the efficacy of dual versus single immune checkpoint inhibitors (ICI) in BRAF wild-type advanced melanoma patients. Materials & methods: A retrospective study of all advanced BRAF wild-type melanoma patients on palliative-intent ICI between 2015 and 2020 (n = 67). Results: Dual ICI had better overall survival (OS) when compared with single ICI in BRAF wild-type patients (hazard ratio: 0.204; 95% CI: 0.064-0.649; p = 0.007), but lost its statistical significance (median OSl not reached vs 20.9 months; p = 0.213; adjusted hazard ratio: 0.475; 95% CI: 0.164-1.380; p = 0.171) when only including patients treated after 2018 when dual ICI was funded in our province. Dual ICI were significantly associated with more frequent (p = 0.005) and severe (p = 0.026) immune-related adverse events, and required more immune-related adverse events-indicated systemic corticosteroid use (p < 0.001) compared with single ICI. Conclusion: While limited by small sample size and retrospective nature, dual ICI may have non statistically significant trend toward better OS efficacy when compared with single ICI in BRAF V600 wild-type advanced melanoma patients.

Long-Term Toxicities of Immune Checkpoint Inhibitor (ICI) in Melanoma Patients.

ICI therapy has greatly improved patient outcomes in melanoma, but at the cost of immune-related adverse events (irAEs). Data on the chronicity of irAEs, especially in real-world settings, are currently limited. We performed a retrospective chart review of 161 adult patients with melanoma treated with at least one cycle of ICI regimen in the adjuvant or metastatic setting: 129 patients received PD-1 inhibitor monotherapy and 32 received dual immunotherapy. Patients were grouped by duration of irAE: permanent (no complete resolution), long-term (resolution over a period ≥ 6 months), transient (resolution over a period < 6 months), or no irAEs. A total of 283 irAEs were reported in the whole patient population. Sixty-six (41.0%) patients developed permanent irAEs, fifteen (9.3%) experienced long-term irAEs as their longest-lasting toxicity, thirty-four (21.1%) developed transient irAEs only, and forty-six (28.6%) experienced no irAEs. Permanent irAEs occurred in 21 (65.6%) patients treated with dual immunotherapy and in 45 (34.9%) patients treated with monotherapy. The majority of permanent irAEs were endocrine-related (36.0%) or skin-related (32.4%). Grade 3-4 permanent irAEs occurred in 20 (12.4%) patients and included toxicities such as adrenal insufficiency, myocarditis, and myelitis. Fifty-three (32.9%) patients were still requiring treatment for long-term or permanent irAEs 6 months or more following the completion of ICI therapy, including twenty-four patients on thyroid hormone replacement and twenty-two on oral steroids. ICI treatment was temporarily interrupted for 64 (22.6%) irAEs and permanently discontinued due to irAEs in 38 patients (13.6% of irAEs, 23.6% of patients); additionally, 4 (2.5%) patients died of irAEs. Our findings show that ICI treatment in melanoma is associated with a wide range of toxicities that can be permanent and may have long-lasting impacts on patients, which should therefore be discussed when obtaining consent for treatment.

No association between BMI and immunotoxicity or clinical outcomes for immune checkpoint inhibitors.

Background: The impact of BMI on immune checkpoint inhibitor toxicity and efficacy has not been clearly characterized. Methods: The authors conducted a retrospective single-center study of patients with advanced unresectable/metastatic cancer initiated on immune checkpoint inhibitors. Results: Of the 409 patients included in the study, 115 (28%) had a BMI ≥30. There was no difference in the development of immune-related adverse events, treatment response or overall survival with respect to BMI <30 versus ≥30 for the whole study population or the melanoma subgroup. Conclusion: Patients with BMI in the obese range (≥30) were not at increased risk of immunotoxicity. Furthermore, BMI was not correlated with treatment response or overall survival in patients receiving immune checkpoint inhibitors.

Several previous studies have suggested that obesity may be correlated with improved efficacy of immunotherapy and raised the concern that obesity may be associated with increased immunotoxicity; however, other studies have not replicated these findings. The authors evaluated the records from one center of 409 patients with advanced cancer on immune checkpoint inhibitors. There was no difference with respect to adverse events, treatment response or survival between obese and nonobese patients.

Complete response and survival outcomes in patients with advanced cancer on immune checkpoint inhibitors.

Aim: To evaluate overall survival in advanced cancer patients who achieved complete response (CR) with immune checkpoint inhibitor (ICI) therapy. Methods: This retrospective study included patients with advanced unresectable or metastatic cancer who received at least one cycle of palliative-intent ICI. Best overall response was used to define response groups. Results: 21 (7%) of 322 patients achieved CR. Multivariate analysis demonstrated that CR was independently associated with better overall survival compared with disease progression (hazard ratio: 0.012; 95% CI: 0.002-0.090) and stable disease (hazard ratio: 0.063; 95% CI: 0.009-0.464) as well as a nonsignificant trend toward better overall survival compared with partial response (hazard ratio: 0.169; 95% CI: 0.023-1.252) regardless of cancer type, ICI regimen or ICI line. Conclusion: Patients who achieved CR had longer survival compared with patients who did not achieve CR.

Real-World Evidence of Systemic Therapy Sequencing on Overall Survival for Patients with Metastatic BRAF-Mutated Cutaneous Melanoma.

Aim: To evaluate optimal systemic therapy sequencing (first-line targeted therapy (1L-TT) vs. first-line immunotherapy (1L-IO)) in patients with BRAF-mutated metastatic melanoma. Methods: Nation-wide prospective data of patients with newly diagnosed BRAF-mutated metastatic melanoma were retrieved from the Canadian Melanoma Research Network. Results: Our study included 79 and 107 patients in the 1L-IO and 1L-TT groups, respectively. There were more patients with ECOG 0−1 (91% vs. 72%, p = 0.023) in the 1L-IO group compared to the 1L-TT group. Multivariable Cox analysis suggested no OS differences between the two groups (HR 0.838, 95%CI 0.502−1.400, p = 0.500). However, patients who received 1L-TT then 2L-IO had the longest OS compared to 1L-IO without 2L therapy, 1L-IO then 2L-TT, and 1L-TT without 2L therapy (38.3 vs. 32.2 vs. 16.9 vs. 6.3 months, p < 0.001). For patients who received 2L therapy, those who received 2L-IO had a trend towards OS improvement compared with the 2L-TT group (21.7 vs. 8.9 months, p = 0.053). Conclusions: Our nation-wide prospective study failed to establish any optimal systemic therapy sequencing in advanced BRAF-mutant melanoma patients. Nevertheless, we provided evidence that immunotherapy has durable efficacy in advanced BRAF-mutant melanoma patients, regardless of treatment line, and that Canadian medical oncologists were selecting the appropriate treatment sequences in a real-world setting, based on patients' clinical and tumour characteristics.

Venous thromboembolism events in patients with advanced cancer on immune checkpoint inhibitors.

Aim: To evaluate the correlation between venous thromboembolism events (VTEs) and immune checkpoint inhibitor (ICI)-based regimens. Methods: This is a retrospective study of 403 patients with advanced cancer on ICI-based regimens. Results: We report 8% VTE incidence post-ICI initiation over a median of 11.1 months of follow-up. Compared with single-agent ICI, dual-ICI was significantly correlated with higher incidence of VTE (odds ratio [OR]: 4.196, 95% CI: 1.527-11.529, p = 0.005), but chemotherapy-immuno-oncology combination was not (OR: 1.374, 95% CI: 0.285-6.632, p = 0.693). Subsequent systemic therapy post-ICI was also independently associated with higher VTE incidence (OR: 2.599, 95% CI: 1.169-5.777, p = 0.019). Conclusion: Our findings suggest potential underreporting of VTE incidence in ICI clinical trials. As dual-ICI is becoming more prevalent in cancer management, clinicians should maintain vigilance regarding VTE in patients with advanced cancer on ICI-based regimens.

Adjuvant Immune Checkpoint Inhibition in Muscle-invasive Bladder Cancer: Is It Ready for Prime Time?

We discuss results from the Checkmate-274 and IMvigor010 trials on adjuvant immune checkpoint inhibitor (ICI) therapy in muscle-invasive bladder cancer (MIBC) with or without neoadjuvant chemotherapy (NAC), and conclude that adjuvant ICI (nivolumab but not atezolizumab) should be considered for patients with resected high-risk MIBC, especially for those who have received NAC.

A case of successful pembrolizumab rechallenge in a patient with non-small-cell lung cancer and grade 3 dermatomyositis.

We report a case of dermatomyositis in a 59-year old female with advanced non-small-cell lung cancer post one cycle of first-line pembrolizumab monotherapy. Her symptoms resolved with high-dose methyl-prednisolone and subsequent prolonged oral prednisone taper over 11 weeks. She achieved durable response over 6 months without further pembrolizumab and was successfully rechallenged without recurrent high-grade immunotoxicity. To our knowledge, this is the only case of severe immune-related dermatomyositis successfully rechallenged with immunotherapy. In this case report, we highlight that dermatomyositis remains a clinical diagnosis with no reliable autoimmune antibody marker. It is a rare immune-related adverse event for which clinicians must remain highly vigilant. We also discuss the rationale and clinical factors to consider on immunotherapy rechallenge decisions.

Prognosticating role of serum eosinophils on immunotherapy efficacy in patients with advanced melanoma.

Aim: To evaluate serum eosinophilia (≥500 peripheral eosinophil counts/microliter) in prognosticating immunotherapy (IO) efficacy. Methodology: A retrospective study of 86 patients with advanced melanoma on PD-1 inhibitors. Results: Eosinophilia-on-IO was an independent prognosticating factor for median OS (HR :0.223; 95% CI: 0.088-0.567; p = 0.002). 'Late eosinophilia' (≥1 year from IO start date) group had better median OS (31.9 vs 24.1 vs 13.0 months; p = 0.002) when compared with 'early eosinophilia' (<1 year from IO start date) and 'no eosinophilia' groups, respectively. Conclusion: Eosinophilia-on-IO and its timing were associated with better IO efficacy in patients with advanced melanoma. Our findings provided insights on potential therapeutic benefit of inducing eosinophilia at certain interval time to obtain a longer durable immunotherapy response.

A single institution study evaluating outcomes of PD-L1 high KRAS-mutant advanced non-small cell lung cancer (NSCLC) patients treated with first line immune checkpoint inhibitors.

AIM: This study aimed to evaluate the impact of KRAS status on the efficacy of first-line immune checkpoint inhibitors (ICI) in patients with advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with advanced incurable or metastatic NSCLC with PD-L1 ≥50% treated with palliative-intent, single-agent PD-1/PD-L1 inhibitors at the Cancer Centre of Southeastern Ontario were included. KRAS mutation status was determined via massively parallel sequencing. Primary study outcome was median overall survival (mOS). RESULTS: Seventy-eight patients (59 non-squamous, 19 squamous) were identified; only non-squamous patients were included in KRAS mutation analyses. Thirty patients (51%) were KRAS-MT (mutant), with G12C (19%), G12V (15%), and G12D (13%) accounting for the most common KRAS mutation subtypes. There was no difference in mOS between KRAS-MT and KRAS-WT (wild-type) patients (12.9 vs. 19.3 months, p = 0.879). There was a non-significant trend towards worse mOS in KRAS G12C patients compared to non-G12C and KRAS-WT patients (11.4 vs. 44.9 vs. 19.3 months, p = 0.772). On multivariable analysis, KRAS-MT status was not associated with mOS (HR 0.901, 95%CI 0.417-1.946, p = 0.791). ECOG≥2 was an independent prognostic factor for worse mOS (HR 2.853, 95%CI 1.237-6.583, p = 0.014). Immune-related adverse events did not differ between KRAS-MT and KRAS-WT groups (48% vs. 52%, p = 1.000). CONCLUSIONS: KRAS mutation status did not have a significant impact on ICI efficacy or safety. However, a non-significant trend towards worse survival was noted in patients treated with ICI whose tumours harboured the KRAS G12C variant. This study provides valuable information for comparative analysis in the future.

A Systematic Review and Meta-analysis of Dual Therapy in Patients With Advanced Renal Cell Carcinoma of Favourable Risk.

OBJECTIVE: To define the impact of first-line dual therapy involving immune checkpoint inhibitors (ICI) on survival outcomes in patients with advanced renal cell carcinoma (aRCC) of International Metastatic RCC Database Consortium favourable-risk. MATERIALS AND METHODS: Systematic review of Medline, EMBASE, and Cochrane Central Register of Controlled trials were conducted to select all phase II/III randomized clinical trials involving first-line, palliative-intent dual therapy in aRCC patients of favourable-risk. Inverse-variance with random-effects model was used for meta-analysis. Sensitivity analysis with exclusion of immune checkpoint inhibitors (ICI)-ICI combination was conducted. Study outcomes were overall survival (OS) and progression free survival (PFS). RESULTS: Seven phase II/III randomized controlled trials (N = 1214) were included in the meta-analysis. There were no significant OS differences detected in the favourable-risk group on dual therapy in comparison to sunitinib monotherapy (HR 0.96, 95%CI 0.73-1.26, P = .79). Sensitivity analysis also did not show significant OS benefit when excluding ICI-ICI regimen (HR 0.99, 95%CI 0.69-1.43, P = .96). PFS was not shown to have significant benefit for dual therapy in the favourable-risk group (HR 0.75, 95%CI 0.50-1.13, P = .17), but it met statistical significance when ICI-ICI regimen was excluded from the analysis (HR 0.63, 95%CI 0.50-0.79, P <.001). CONCLUSION: There was no OS benefit when comparing dual therapy vs sunitinib monotherapy in aRCC favourable-risk group. Longer follow-up would be required to definitively detect potential OS benefit, if any. Careful patient-clinician discussion of alternative management options are required prior to initiating dual-therapy in all aRCC favourable-risk group.

Impact of Baseline Corticosteroids on Immunotherapy Efficacy in Patients With Advanced Melanoma.

This is a 2-center, retrospective study which aimed to evaluate the effect of baseline corticosteroid use on immunotherapy efficacy in patients with advanced melanoma. We included all patients with advanced unresectable and metastatic melanoma on single-agent programmed cell death protein 1 (PD-1) inhibitors at the Cancer Centre of Southeastern Ontario and London Regional Cancer Program. We defined baseline corticosteroid use as prednisone-equivalent of ≥10 mg within 30 days of immunotherapy initiation. Our study had 166 patients in total, and 25 were taking corticosteroids at the initiation of the PD-1 inhibitor. Baseline prednisone-equivalent ≥10 mg did not have effect on median overall survival (hazard ratio=1.590, 95% confidence interval: 0.773-3.270, P=0.208). However, a higher dose of baseline prednisone-equivalent ≥50 mg was independently associated with poor median overall survival (hazard ratio=2.313, 95% confidence interval: 1.103-4.830, P=0.026) when compared with baseline prednisone-equivalent 0-49 mg, even when controlled for confounders including baseline Eastern Cooperative Oncology Group ≥2 and baseline brain metastasis. Consideration should be made to decrease the use of unnecessary steroids as much as possible before initiation of PD-1 inhibitor treatment.

Safety of Immunotherapy Rechallenge After Immune-related Adverse Events in Patients With Advanced Cancer.

This retrospective study aimed to investigate the safety profile of continuing or rechallenging patients with advanced cancer who developed grade≥2 immune-related adverse events (irAEs) on immunotherapy-based regimens. Our study had 25, 20, and 40 patients (N=85) in the Treatment Continuation (TCG), Non-Rechallenge (NRG), and Rechallenge Groups (RG), respectively. Subsequent irAEs recurrence were more common in RG than TCG and NRG (78% vs. 56% vs. 25%, P<0.001). The same subsequent irAEs recurrences occurred on 42% of RG, 4% of TCG, and 15% of NRG (P<0.001). On the RG, there was a nonstatistical trend of shortening interval time between time from treatment rechallenge to subsequent irAEs when compared with time from first treatment to initial grade≥2 irAEs (5.86 vs. 8.86 wk, P=0.114). Patients who had cardiac irAEs were not rechallenged. Several high-risk features were identified to prognosticate risk of irAEs recurrences upon treatment rechallenge, including age 65 years and above (P=0.007), programmed cell death protein 1 inhibitors (P<0.001), grade 3 irAEs (P=0.003), pneumonitis type (P=0.048), any systemic corticosteroid use (P=0.001)/high-dose systemic corticosteroid use (P=0.007)/prolonged ≥4-week corticosteroid use (P=0.001) for irAEs management, and early development of irAEs (P=0.003). Our study concluded that it was relatively safe to continue or rechallenge patients with advanced cancers on immunotherapy-based regimens postdevelopment of certain grade≥2 irAEs, except for cardiac, neurological, or any grade 4 irAEs. Subsequent irAEs were common, no more severe, involved the same organ sites, and occurred more quickly than the original irAE. Close monitoring of all potential irAEs is required when rechallenging a patient on immunotherapy, especially for patients with high-risk features.